Original articles

Vol. 117: Issue 3 - June 2025

Homologous recombination deficiency testing in ovarian cancer: the diagnostic experience of a referral Italian institution

Authors

Key words: ovarian neoplasms, point of care testing, molecular pathology
Publication Date: 2025-07-04

Abstract

Aims. Recently, precision medicine has drastically modified clinical paradigm for the clinical stratification of high-grade serous ovarian cancer (HGSOC) patients. International societies approved poly (ADP-ribose) polymerase (PARP) inhibitors (PARPIs) to treat platinumsensitive BRCA1/2 defective HGSOC patients. Beyond BRCA1/2, functional defects in homologous recombination repair (HRR) proteins laid the basis for genomic instability evaluation in HGSOC patients. Given that measurement of homologous recombination deficiency (HRD) is extremely complex molecular analysis is outsourced. Of note, this diagnostic algorithm is affected by inconclusive results and high rejection rates. Here, we review the molecular results of BRCA1/2 and HRD analysis from referral institution in predictive molecular pathology.
Methods. From May 2023 to Jan 2024 molecular records from 147 HGSOC patients simultaneously tested for BRCA1/2 and HRD measurement were inspected. A commercially available next-generation sequencing (NGS) panel (Amoy Diagnostics Co Ltd, Xiamen, Fujian, China) was adopted to internally perform molecular analysis on formalin-fixed paraffin- embedded (FFPE) samples. In a subset of patients clinical records were matched with molecular results.
Results. Overall, 2 out of 147 (1.3%) cases were morphologically classified as inadequate. Simultaneous BRCA1/2 - HRD analysis was successfully assessed in 112 out of 145 (77.2%) patents. Molecular analysis revealed 7 out of 112 (6.2%) and 2 out of 112 (1.8%) pathogenetic or likely pathogenetic (class I-II) and variants of uncertain significance (VUS) (class III) BRCA1/2 molecular alterations, respectively. HRD score was positive in 48 out of 112 (42.8%) HGSOC patients.
Conclusions. HRD testing is a reliable method for the clinical management of HGSOC patients.

Introduction

To date, ovarian cancer (OC) consists of most leading cause of death, worldwide, among gynecological malignancies 1. In particular, high-grade serous ovarian cancer (HGSOC), mostly diagnosed in advanced stage (II-IV) in accordance with The International Federation of Gynecology and Obstetrics (FIGO) classification system, is affected by unfavorable prognosis and worst clinical outcome 2. In this scenario, optimized therapeutic strategies play a pivotal role in the clinical management of HGSOC patients. Nowadays, platinum-based chemotherapy in combination with surgery is considered the standard of care for the routine management of OC patients 3. In the last years, precision medicine has revolutionized the landscape of clinically available treatments for HGSOC patients 4. Among these, poly (ADP-ribose) polymerase (PARP) inhibitors (PARPIs) emerged as novel targeted approach for HGSOC patients defective in homologous recombination repair (HRR) system 5-7. Firstly, PARPi were approved by international societies for the treatment of platinum-sensitive HGSOC patients showing germline or somatic BRCA1/2 pathogenetic alterations 8,9. Of note, activity of the HRR depends on a plethora of equally crucial actors involved, like BRCA1/2, in maintenance of DNA integrity 10,11. In this regard,, functional defects in HRR proteins, classified as homologous recombination deficiency (HRD) status, activate error-prone DNA repair mechanisms laying the basis for genomic instability and evolutionary neoplastic cell transformation 12) Clinical trials investigated the role of HRD status for the stratification of HGSOC patients electing to PARPi administration. It has been certainly showed that HRD positive HGSOC patients had a favorable clinical outcome in comparison with HRR-proficient tumors 12-14. Remarkably, HRD status is measured by bioinformatic tools able to calculate “genomic scar” from next generation sequencing (NGS) data integrating loss of heterozygosity (LOH), telomeric allelic imbalance (TAI) and large-scale state transitions (LST) 15-17. Regarding technical aspects, NGS platforms that allow molecular analysis of comprehensive genomic regions, measure HRD score integrating optimized bioinformatic algorithm 15. In fact, PARPi registrative clinical trials evaluated BRCA1/2 molecular alterations and HRD score adopting an outsourcing approach based on centralized molecular testing 13,14. However, a not-negligible rejection rate (5-25%), extensive turnaround time (TAT) and the lack of standardized preanalytical procedures dramatically impacts on the molecular testing of HRD score on diagnostic routine samples 18,19. In this scenario, commercially available diagnostic assays have been developed to implement in-house HRD testing as a partially resolutive strategy to improve the success rate of HRD molecular analysis 19. Being affected by technical and analytical pitfalls, harmonized analytical workflows and data interpretating system are required to definitively implement this diagnostic strategy in clinical practice 18-20. Not surprisingly, our Molecular Predictive Pathology Laboratory at the Department of Public Health of the University of Naples Federico II routinely adopts in-house NGS assays for BRCA1/2 and HRD evaluation on diagnostic routine specimens from HGSOC patients. Here, we review our molecular records from NGS analysis of HGSOC patients inspected for clinically relevant BRCA1/2 variants and HRD status evaluation. To clinically validate our diagnostic workflow, molecular data were also matched with clinical outcomes in a representative series of HGSOC patients.

Study design

From May 2023 to January 2024 molecular records from 147 HGSOC patients simultaneously tested for BRCA1/2 pathogenetic alterations and HRD measurement were retrieved from internal archive of University of Naples Federico II. For each patient a formalin fixed paraffin embedded (FFPE) representative of tumor lesion was available for molecular analysis adopting a commercially available NGS assay (Amoy Diagnostics Co Ltd, Xiamen, Fujian, China) integrating BRCA1/2 clinically informative molecular alterations and HRD measurement. Written informed consent was acquired from all patients and documented according to “The Italian Data Protection Authority” (http://www.garanteprivacy.it/web/guest/home/docweb/-/docwebdisplay/export/2485392). All information regarding human material was managed using anonymous numerical codes and all samples were handled in compliance with the Helsinki Declaration (http://www.wma.net/en/30publications/10policies/b3/).

Material and methods

For each patient, a series of four unstained slides (5 μm), matched with hematoxylin/eosin (H/E) stained slide representative of tumor lesion, were prepared to perform nucleic acid purification. An expert pathologist internally reviewed each case counting neoplastic cell percentage available to extract nucleic acids. Briefly, DNA extraction was realizing using QiAmp Mini Kit (Qiagen, Hilden, Germany) following manufacturer’s instructions. Two platforms were used to evaluate DNA concentration: Qubit fluorimeter 2.0 (Thermofisher Scientifics, Waltham, Massachusetts, USA) and TapeStation 4200 (Agilent, Santa Clara, California, USA) in accordance with technical guidelines 22) In particular, TapeStation 4200 (Agilent, Santa Clara, California, USA) also enabled to calculate DNA integrity number (DIN), reflecting fragmentation index of nucleic acids 22. NGS analysis was carried out adopting the Amoy HRD focus panel (Amoy Diagnostics Co Ltd, Xiamen, Fujian, China) on NextSeq 550 Dx system (Illumina, San Diego, USA). This panel includes SNVs and indels in coding/noncoding regions from 27 HRR-related genes plus hot spot mutations in 5 tumor informative genes among solid tumor patients. Halo-shape Annealing and Defer-Ligation Enrichment systems, derived from Molecular Inversion Probe (MIP) technology, were used for selecting target regions on genomic DNA. An optimized workflow was implemented batching 8 samples in each run to improve the success rate of molecular analysis on scant diagnostic samples. After DNA extension, circular DNA was repaired by manufacturer ligase enzyme and then cleaved by exonucleases in order to create single strand DNA for templating and sequencing procedures on NextSeq 550 Dx platform (Illumina, San Diego, USA). Data processing, BRCA1/2 variants and HRD scoring (GSS score) was approached on proprietary analysis software. In particular, GSS score greater than or equal to 50 revealed HRD positive status, in accordance with manufacturer procedures. Technically relevant quality metrics (median coverage, alignment percentage, BRCA medium effective depth, SNP medium effective depth, SNP uniformity) were manually inspected stratifying samples in accordance with the technical requirement of molecular testing. Briefly, if samples failed in a single quality metrics, the molecular report was successfully accepted; if 2 ≥ quality metrics < 4 were failed molecular results were classified as “suboptimal” whereas samples affected by 4 not surpassing quality metrics were diagnosed as “failed”.

Results

Overall, 2 out of 147 (1.3%) diagnostic specimens were diagnosed as inadequate after morphological evaluation. In the remaining cases, our internally optimized NGS based workflow was able to successfully carry out n = 112 out of 145 (77.2%) molecular analyses both for HRD scoring and BRCA1/2 in diagnostic routine HGSOC patients. By considering technical parameters, a neoplastic cell percentage median value of 56.0 % (ranging from 10.0 to 90.0%) were calculated to recover nucleic acids for molecular testing. In addition, nucleic acid purification yielded a median value of 40.0 ng/μL (ranging from 1.3 to 60.0 ng/μL). Moreover, DNA concentration was also estimated by adopting TapeStation 4200 (Agilent) in 96 out of 112 (85.7%). In this series, nucleic acids showed a median value of 28.5 ng/μL (ranging from 3.2 to 120.0 ng/μL). DIN was successfully calculated in each instance highlighting a median value of 3.2 (ranging from 1.4 to 6.3) (Tab. I). Overall, a median coverage of 99.8 % (ranging from 98.4 to 100.0%), alignment percentage of 96.2% (ranging from 78.1 to 99.0 %), BRCA medium effective depth of 1329.7 (ranging from 124.0 to 4699.0) BRCA uniformity of 98,6% (ranging from 92.5 to 100.0%), SNP medium effective depth of 187.7 (ranging from 16.0 to 570.0) and SNP uniformity of 93.4% (ranging from 86.7 to 97.0%) were identified (Tab. II). As showed by NGS analysis, 7 out of 112 (6.2%) and 2 out of 112 (1.8%) HGSOC patients harbored pathogenetic or likely pathogenetic (class I-II) and Variants of Uncertain Significance (VUS) (class III) BRCA1/2 molecular alterations, respectively, in accordance with AMP/CAP/ASCO/ACMG international guidelines 21. Among BRCA1/2 mutated patients, 4 out of 9 (44.4%) and 5 out of 9 (55.6%) mutated displayed BRCA1 and BRCA2 molecular alterations, respectively. In detail, 4 out of 9 (44.4%) and 5 out of 9 (55.6%) single nucleotide variants (SNVs) and small deletions or insertions were detected. A single alteration was detected in a BRCA1 non-coding region. In addition, HRD measurement highlighted a positive GS score in 48 out of 112 (42.8%) HGSOC patients (Tab. III).

Sixteen out of 147 patients who underwent testing for BRCA1/2 pathogenic alterations and HRD measurement were referred to the Oncology Department of our University Hospital for clinical care. The baseline characteristics of these patients are detailed in Table IV. The median age at diagnosis was 61 years. All patients were diagnosed with HGSOC. One patient had FIGO stage I disease, while 11 patients had stage III, and four had stage IV. In the context of surgical treatment, 9 patients received primary debulking surgery (PDS), while 4 underwent interval debulking surgery (IDS) after receiving 3 cycles of neoadjuvant platinum-based chemotherapy and 3 after 6 cycles of platinum-based chemotherapy. Among the six patients whose chemotherapy response scores (CRS) were evaluated, three exhibited a minimal tumor response (CRS1), one displayed a partial tumor response (CRS2), and two achieved a complete tumor response (CRS3). The surgical outcomes were as follows: no residual disease (R0) in twelve patients, tumor residue of less than one centimeter (R1) in two, and tumor residue of greater than one centimeter (R2) in two others. All patients received chemotherapy comprising carboplatin AUC5 + paclitaxel 175 mg/m2 every 21 days for a total of six cycles. Among the 16 patients, 15 underwent maintenance therapy, with three receiving bevacizumab, five receiving olaparib, six receiving niraparib, and one receiving olaparib in combination with bevacizumab. Currently, the maturation of survival events has not yet reached a level that would allow for the identification of relationships between particular clinical features and oncological results.

Discussion

The rapidly evolving scenario of predictive biomarkers lay the basis for novel therapeutic algorithm in the management of HGSOC patients in clinical practice 2,23. BRCA1/2 pathogenic alterations select HGSOC patients to PARPi administration stratifying patients that could benefit from a targeted approach 3-9. In the last years, HRD status has been elected as integrating biomarker able to identify HGSOC patients administrable with PARPi. Several clinical trials highlighted a statistically significant favorable outcome in HGSOC patients under PARPi administration demonstrating the clinical efficacy of BRCA1/2-HRD molecular analysis in a diagnostic routine setting. To date, HRD status is calculated by externalized NGS based assays able to measure genomic scar integrating molecular hallmarks behind DNA instability. In particular, outsourced diagnostic strategies are affected by high turnaround time (TAT), low sustainable technical cost and a non-negligible rejection rate (30.0-40.0%) drastically reducing the widespread diffusion of externalized systems in diagnostic routine practice. In this regard, a plethora of commercially available NGS assays measuring HRD score may be adopted to internally carry out HRD analysis in institutions involved in precision medicine. Despite the lack of clinical validation, the implementation of in-house HRD testing strategies overcomes technical and logistic issues of externalized testing approaches reducing rejection rate and TAT 19. Start new paragraph we overviewed our diagnostic workflow for detecting BRCA1/2 clinically informative alterations and calculating HRD score in a retrospective series of HGSOC patients by a commercially available NGS assay. Interestingly, 112 out of 145 (77.2%) HGSOC patients were successfully analyzed for both BRCA1/2 and HRD status suggesting an adequate successful rate of molecular profiling in a series of real-world samples. In addition, our approach successfully detected clinically impactful BRCA1/2 mutations in 8.0% of HGSOC patients. Among them, 6.2% (7 out of 112) and 1.8% (2 out of 112) cases revealed BRCA class I-II and class III molecular alterations, respectively. Moreover, HRD status was detected in 42.8% (48 out of 112) patients. In this scenario, pre-analytical procedures of managing diagnostic specimens dramatically impact their suitability for molecular profiling. Regarding median DIN value, microfluidic system listed successfully tested HGSOC patients in A (1 < DIN < 2), B (2≤DIN < 3) and C (3≤DIN) groups (Supplementary Table I). Interestingly, samples affected by > 4 did not surpass quality metrics; 2 ≥ quality metrics < 4 failed matched with group A and B, respectively, while diagnostic samples with optimal technical parameters were listed in group C (Supplementary Table I) (Fig. 1). The latest point strongly suggests the central role of optimized preanalytical management of diagnostic routine samples to improve the success rate in of HGSOC patients. Interestingly, NGS failed samples highlighted a median DIN value of 1.7 (ranging from 1.0 to 4.1) demonstrating the central role of pre-analytical procedures to maintain DNA integrity (Supplementary Table II) (Supplementary material) 24.

In conclusion, we evaluated a referral laboratory experience on integrated BRCA1/2-HRD molecular analysis in unselected HGSOC patients from our diagnostic routine practice supporting the key role of in-house comprehensive NGS analysis to decrease the rejection rate and TAT to optimize the clinical stratification of HGSOC patients. Further studies are recommended to clinically validate these technical strategies matching molecular and clinical records from a large cohort of HGOSC patients eligible for molecular analysis for PARPi administration.

CONFLICT OF INTEREST STATEMENT

F.P. has relevant relationship (advisory fees, honoraria, travel accommodation and expenses, grants and non-financial support) with Menarini, Roche unrelated to the current work. U.M. has received personal fees (as consultant and/or speaker bureau) from Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientifics, Eli Lilly, Diaceutics, GSK, Merck and AstraZeneca, Janssen, Diatech, Novartis and Hedera unrelated to the current work. G.T. reports personal fees (as speaker bureau or advisor) from Roche, MSD, Pfizer, Boehringer Ingelheim, Eli Lilly, BMS, GSK, Menarini, AstraZeneca, Amgen and Bayer, unrelated to the current work. M.B. has received honoraria for consulting, advisory role, speakers’ bureau, travel, accommodation, expenses from MSD Oncology, Roche/Genetech, Astra Zeneca, Thermofisher Scientific, GSK and Illumina unrelated to the current work.

FUNDING

The Italian Health Ministry’s research program (ID: NET-2016-02363853). National Center for Gene Therapy and Drugs based on RNA Technology MUR-CN3 CUP E63C22000940007 to DS.

ETHICAL CONSIDERATION

All information regarding human material was managed using anonymous numerical codes, and all samples were handled in compliance with the Helsinki Declaration.

AUTHORS CONTRIBUTION

Conceptualisation: FP, GR, GT, UM. Methodology: all authors. Software: all authors. Validation: all authors. Formal analysis: all authors. Investigation: all authors. Resources: all authors. Data curation: all authors. Writing—original draft preparation: FP, GR, Writing—review and editing: all authors. Visualisation: all authors. Supervision: UM, GT. Project administration: UM and GT. Funding acquisition: GT, UM

Supplementary material

PRE-ANALYTICAL PROTOCOL (PART I)

Cold ischemia covering the timing gap tissue surgical remotion and fixation procedure may impact on morphological and molecular evaluation of tissue samples. Particularly, Neutral buffered formalin (NBF) fixation should be approached within 6 h from surgery to reduce the ischemic process and drastically decrease degradation rate of nucleic acids (DNA >24 h, RNA >12 h). NBF penetrate tissues at 1 mm/h and should be adopted within 24 h after dilution to 4% w/v). Remarkably, longer fixation time (DNA>72 h, RNA>48 h) also increases degradation rate of nucleic acids drastically impacting on the successful implementation of molecular techniques on over-fixed diagnostic routine samples. Although formalin fixed paraffin embedding (FFPE) tissue preserving approach represents the most common strategy to collect tissue specimens in diagnostic routine setting. It has been recommended to maintain paraffin at 56°C during tissue inclusion and archive FFPE samples <15°C.

PRE-ANALYTICAL PROTOCOL (PART II)

Neoplastic cell percentage should be ≥25.0-30.0% to successfully elect FFPE samples to molecular test. After DNA extraction, input recommendation is defined by technical specification of each assay (e.g. Amoy HRD focus panel requires almost 50 ng to successfully carry out molecular analysis). In terms of nucleic acids fragmentation, TapeStation 4200 (Agilent) platform highlighted that samples are grouped as follows inspecting DNA integrity number (DIN):

  • 0<DIN<2= samples failed to NGS analysis; >4 quality checks do not meet technical cut-off (median coverage, alignment percentage, BRCA medium effective depth, SNP medium effective depth, SNP uniformity)
  • 2<DIN<3= samples were suboptimal to NGS analysis; 2< quality checks <4 do not meet technical cut-off (median coverage, alignment percentage, BRCA medium effective depth, SNP medium effective depth, SNP uniformity)
  • DIN >3= samples were successfully analyzed on NGS analysis; quality checks >4 meet technical cut-off (median coverage, alignment percentage, BRCA medium effective depth, SNP medium effective depth, SNP uniformity)
ID DIN N° of Not Optimal Analytical Metrics
Group A 81 1.0 5
86 1.0 5
69 1.1 5
75 1.3 5
33 1.4 2
63 1.4 Failed analysis
64 1.4 4
65 1.4 6
79 1.4 5
83 1.4 4
84 1.4 5
29 1.5 1
37 1.5 4
52 1.5 6
77 1.5 5
82 1.5 5
7 1.6 4
68 1.6 5
3 1.7 4
16 1.7 2
67 1.7 5
40 1.8 4
50 1.8 2
1 1.9 4
27 1.9 1
57 1.9 1
71 1.9 3
Group B 28 2.0 3
43 2.0 1
55 2.0 3
56 2.0 5
58 2.0 2
66 2.0 Failed analysis
73 2.0 2
74 2.0 2
11 2.1 1
48 2.1 2
8 2.2 2
10 2.2 1
44 2.2 4
146 2.2 1
5 2.3 1
9 2.3 2
13 2.3 2
35 2.3 1
6 2.4 1
15 2.4 1
17 2.4 0
30 2.4 1
45 2.4 1
47 2.4 1
53 2.4 1
54 2.4 1
18 2.5 0
41 2.5 1
61 2.5 3
70 2.5 0
80 2.5 4
106 2.5 2
21 2.6 1
23 2.6 0
31 2.6 1
38 2.6 1
39 2.6 1
140 2.6 0
147 2.6 5
24 2.7 2
25 2.7 1
34 2.7 1
49 2.7 1
78 2.7 1
95 2.7 0
135 2.7 2
2 2.8 1
4 2.8 1
20 2.8 0
36 2.9 1
76 2.9 2
110 2.9 1
Group C 32 3.0 1
42 3.0 0
46 3.0 1
51 3.0 0
125 3.0 0
136 3.0 0
12 3.1 0
26 3.1 1
132 3.1 1
141 3.1 0
59 3.2 2
131 3.2 1
104 3.3 0
127 3.3 3
138 3.3 0
14 3.4 0
22 3.4 1
142 3.4 1
134 3.5 0
94 3.6 0
62 3.7 3
91 3.7 0
100 3.7 1
139 3.7 1
92 3.8 0
137 4.0 0
109 4.1 5
19 4.2 0
144 4.3 1
115 4.4 0
118 4.4 1
130 4.6 0
114 4.7 0
143 4.7 0
145 4.7 0
120 5.0 0
102 5.5 0
133 5.5 0
117 5.7 0
108 6.0 2
124 6.0 1
98 6.1 0
122 6.1 0
128 6.3 0
129 6.3 0
Abbreviations: DIN (DNA Integrity number).
Supplementary Table I. List of patients with DNA quality assessment compared with their molecular analysis results. Samples were grouped in Group A (1<DIN<2), Group B (2≤DIN<3) and Group C (3≤DIN).
ID CN% Histological Diagnosis DIN ng/μl (TapeStation 4200) ng/μl (Qubit)
1 20% HGSOC 1.9 7.3 0.9
3 60% HGSOC 1.7 5.3 1.3
7 20% HGSOC 1.6 4.0 0.5
37 90% HGSOC 1.5 4.6 17.0
40 60% HGSOC 1.8 2.7 9.2
44 20% HGSOC 2.2 9.4 2.9
52 40% HGSOC 1.5 5.4 1.8
55 60% HGSOC 2.0 13.5 28.2
56 60% HGSOC 2.0 7.7 18.6
60 20% HGSOC - 0.8 0.6
63 20% HGSOC 1.4 1.5 0.6
64 50% HGSOC 1.4 7.3 30.1
65 15% HGSOC 1.4 4.3 2.0
66 30% HGSOC 2.0 4.1 1.4
67 15% HGSOC 1.7 2.9 0.2
68 20% HGSOC 1.6 4.3 1.0
69 50% HGSOC 1.1 3.2 0.6
71 20% HGSOC 1.9 5.7 1.5
75 50% HGSOC 1.3 3.7 0.2
77 40% HGSOC 1.5 4.4 4.1
79 25% HGSOC 1.4 4.9 1.5
80 30% HGSOC 2.5 4.2 2.4
81 40% HGSOC 1.0 2.5 2.6
82 80% HGSOC 1.5 6.1 2.1
83 80% HGSOC 1.4 6.4 1.4
84 90% HGSOC 1.4 3.3 11.4
86 25% HGSOC 1.0 3.3 0.6
89 70% HGSOC NA NA 5.8
109 70% HGSOC 4.1 2.8 2.2
112 70% HGSOC - 1.3 0.8
116 70% HGSOC NA NA 0.5
126 30% HGSOC NA NA 0.6
147 60% HGSOC 2.6 3.1 2.6
Supplementary Table II. Quality and quantity parameters of NGS failed samples.

History

Received: September 24, 2025

Accepted: November 24, 2025

Figures and tables

Figure 1. Exemplificative grouping (A, B, C) system to distinguish samples on the basis of technical parameters: DNA fragmentation index and NGS quality check drastically impacts the failure rate of molecular testing.

ID NC% DIN ng/μl (TapeStation 4200) ng/μl (Qubit)
1 20% 1.9 7.3 0.9
2 60% 2.8 29.8 60.0
3 60% 1.7 5.3 1.3
4 70% 2.8 45.8 60.0
5 20% 2.3 8.2 3.2
6 30% 2.4 20.8 26.2
7 20% 1.6 4.0 0.5
8 30% 2.2 12.7 12.9
9 70% 2.3 13.5 19.8
10 60% 2.2 19.4 39.4
11 20% 2.1 6.5 15.9
12 40% 3.1 21.1 58.0
13 70% 2.3 11.8 9.2
14 40% 3.4 17.7 35.6
15 30% 2.4 16.6 25.0
16 30% 1.7 4.4 1.3
17 60% 2.4 9.7 34.9
18 70% 2.5 28.2 59.0
19 70% 4.2 96.0 60.0
20 60% 2.8 19.9 38.5
21 50% 2.6 5.5 4.3
22 30% 3.4 11.4 16.7
23 70% 2.6 61.9 60.0
24 20% 2.7 7.3 7.2
25 80% 2.7 7.8 13.3
26 60% 3.1 20.7 32.0
27 60% 1.9 12.7 2.9
28 40% 2.0 8.9 3.0
29 30% 1.5 4.9 6.0
30 60% 2.4 9.1 24.3
31 60% 2.6 88.3 51.0
32 60% 3.0 45.7 40.9
33 30% 1.4 6.8 5.8
34 80% 2.7 51.0 36.4
35 60% 2.3 48.9 42.0
36 60% 2.9 15.7 25.3
37 90% 1.5 4.6 17.0
38 70% 2.6 40.0 44.2
39 60% 2.6 9.7 5.9
40 60% 1.8 2.7 9.2
41 50% 2.5 25.3 39.0
42 80% 3.0 94.5 60.0
43 60% 2.0 9.0 5.1
44 20% 2.2 9.4 2.9
45 30% 2.4 19.9 11.7
46 30% 3.0 20.5 29.3
47 20% 2.4 16.2 11.4
48 60% 2.1 24.8 40.9
49 50% 2.7 49.4 45.4
50 70% 1.8 36.1 37.2
51 70% 3.0 60.2 56.0
52 40% 1.5 5.4 1.8
53 70% 2.4 20.8 25.2
54 50% 2.4 33.0 43.5
55 60% 2.0 13.5 28.2
56 60% 2.0 7.7 18.6
57 70% 1.9 8.5 39.0
58 60% 2.0 25.7 51.0
59 30% 3.2 3.8 3.3
60 20% - 0.8 0.6
61 10% 2.5 13.7 11.0
62 50% 3.7 16.4 21.6
63 20% 1.4 1.5 0.6
64 50% 1.4 7.3 30.1
65 15% 1.4 4.3 2.0
66 30% 2.0 4.1 1.4
67 15% 1.7 2.9 0.2
68 20% 1.6 4.3 1
69 50% 1.1 3.2 0.6
70 75% 2.5 17.4 19.9
71 20% 1.9 5.7 1.5
72 70% Inadequate
73 40% 2.0 6.5 4.6
74 75% 2.0 13.2 19.2
75 50% 1.3 3.7 0.2
76 90% 2.9 5.1 7.5
77 40% 1.5 4.4 4.1
78 90% 2.7 24.1 38.4
79 25% 1.4 4.9 1.5
80 30% 2.5 4.2 2.4
81 40% 1.0 2.5 2.6
82 80% 1.5 6.1 2.1
83 80% 1.4 6.4 1.4
84 90% 1.4 3.3 11.4
85 5% Inadequate
86 25% 1.0 3.3 0.6
87 70% NA NA 37.9
88 80% NA NA 15.5
89 70% NA NA 5.8
90 70% NA NA 14.0
91 60% 3.7 42.6 60.0
92 70% 3.8 33.4 48.0
93 70% NA NA 60.0
94 60% 3.6 10.6 39.5
95 40% 2.7 87.8 60.0
96 80% NA NA 60.0
97 60% NA NA 34.4
98 20% 6.1 19.8 11.8
99 70% NA NA 60.0
100 40% 3.7 15.0 16.4
101 10% NA NA 39.5
102 30% 5.5 20.4 11.6
103 80% NA NA 37.3
104 40% 3.3 28.8 25.0
105 50% NA NA 25.0
106 70% 2.5 3.2 30.7
107 20% NA NA 5.0
108 60% 6.0 11.6 2.2
109 70% 4.1 2.8 2.2
110 60% 2.9 34.3 47.9
111 60% NA NA 45.9
112 70% - 1.3 0.8
113 50% NA NA 60.0
114 70% 4.7 37.4 8.7
115 50% 4.4 41.1 35.3
116 70% NA NA 0.5
117 60% 5.7 28.8 60.0
118 90% 4.4 12 43.2
119 60% NA NA 31.5
120 60% 5.0 105.0 60.0
121 60% NA NA 38.7
122 60% 6.1 14.0 24.0
123 70% NA NA 43.8
124 50% 6.0 14.6 19.4
125 50% 3.0 85.5 24.9
126 30% NA NA 0.6
127 60% 3.3 22.0 6.9
128 90% 6.3 88.3 60.0
129 60% 6.3 30.2 60.0
130 30% 4.6 21.4 23.1
131 70% 3.2 30.6 30.0
132 40% 3.1 3.7 5.8
133 40% 5.5 29.6 28.2
134 70% 3.5 14.7 30.3
135 70% 2.7 17.2 40.7
136 80% 3.0 47.9 43.8
137 70% 4.0 108.0 60.0
138 30% 3.3 11.8 6.64
139 70% 3.7 9.5 11.1
140 40% 2.6 7.9 8.6
141 70% 3.1 120.0 58.0
142 80% 3.4 19.9 33.2
143 90% 4.7 94.2 60.0
144 70% 4.3 10.1 22.4
145 70% 4.7 10.3 28.2
146 70% 2.2 10.7 14.7
147 60% 2.6 3.1 2.6
Abbreviations: DIN (DNA Integrity Number); HGSOC (High-Grade Serous Ovarian Cancer); NA (Not Assessed); NC% (Neoplastic Cells Percentage); ng (nanograms); μl (microliters).
Table I. Histological characteristics and DNA quantity and quality evaluated by using Qubit and TapeStation 4200 systems.
ID Production Total Reads Coverage BRCA Effective Depth BRCA Uniformity SNP Effective Depth SNP Uniformity
2 2.16G 19913472 99.9% 817 100.0% 164 96.1%
4 2.01G 18571616 99.9% 979 100.0% 189 96.4%
5 1.73G 16474232 99.8% 435 99.2% 66 92.1%
6 2.03G 18367404 99.9% 778 99.6% 100 94.5%
8 1.74G 17425778 99.4% 174 95.7% 33 90.3%
9 1.72G 21884288 99.8% 388 95.7% 98 91.3%
10 1.75G 21398172 99.9% 582 99.6% 80 93.7%
11 5.52G 50918844 99.9% 511 99.2% 79 94.1%
12 4.62G 41335728 99.9% 2827 100.0% 427 96.9%
13 3.99G 37815908 99.6% 152 97.6% 28 93.7%
14 4.33G 38975284 99.9% 2661 98.8% 323 95.8%
15 3.84G 34455110 99.9% 1154 99.6% 148 95.2%
16 3.94G 36940658 98.4% 124 96.5% 19 89.8%
17 4.58G 41698228 99.9% 871 99.6% 219 95.8%
18 4.34G 39156410 99.9% 2158 100.0% 277 96.1%
19 3.72G 33514812 99.9% 2587 99.6% 295 96.2%
20 4.09G 37142410 99.9% 1067 100.0% 177 95.9%
21 4.31G 38692248 99.9% 725 96.9% 96 90.8%
22 4.72G 41886534 99.9% 1259 99.2% 133 91.3%
23 4.52G 40647830 99.9% 1364 100.0% 229 96.5%
24 4.76G 42715040 99.8% 660 96.9% 92 89.9%
25 4.64G 41669086 99.9% 921 98.4% 164 93.0%
26 4.58G 41224262 99.9% 1359 99.6% 191 94.5%
27 4.31G 38829700 99.8% 502 97.2% 75 91.6%
28 4.51G 41530520 99.7% 270 96.1% 65 89.1%
29 4.55G 42401678 99.8% 422 99.2% 50 95.7%
30 4.53G 40806372 99.9% 1422 99.2% 191 93.6%
31 4.70G 42825632 99.9% 1203 99.2% 170 95.2%
32 4.96G 44837466 99.9% 1330 100.0% 178 95.1%
33 4.44G 43733852 99.5% 171 99.6% 26 92.7%
34 4.58G 41035748 99.9% 1046 98.0% 155 94.3%
35 4.42G 40583668 99.9% 773 99.6% 117 93.7%
36 4.64G 42201522 99.9% 817 100.0% 70 94.7%
38 4.43G 40157424 99.9% 838 99.6% 120 94.4%
39 3.90G 35460700 99.7% 698 96.5% 76 90.3%
41 4.82G 43868824 99.9% 813 99.2% 126 95.5%
42 4.42G 40131068 99.9% 1100 100.0% 208 95.8%
43 4.36G 40299812 99.8% 398 98.4% 51 94.0%
45 4.84G 43556400 99.9% 840 97.2% 144 93.9%
46 4.56G 40586888 99.9% 1299 98.8% 116 92.4%
47 4.91G 44813608 99.8% 402 96.1% 81 91.4%
48 4.84G 44602962 99.9% 393 98.0% 86 92.4%
49 4.80G 43460562 99.9% 916 99.6% 152 94.8%
50 4.55G 42126022 99.9% 183 99.6% 62 95.9%
51 4.84G 43737052 99.9% 1289 98.8% 210 93.8%
53 3.89G 35529636 99.9% 695 99.6% 121 92.9%
54 3.47G 31529008 99.9% 1197 98.8% 145 93.9%
57 4.12G 37473492 99.9% 1209 99.6% 119 95.1%
58 4.28G 39907842 99.9% 241 99.6% 57 94.4%
59 3.96G 37690392 99.7% 446 97.2% 60 89.7%
61 3.94G 36170532 99.8% 766 92.5% 123 86.8%
62 3.95G 35957586 99.9% 1144 94.5% 145 89.0%
70 4.20G 39425048 99.9% 1079 99.2% 140 94.5%
73 4.16G 45260928 99.7% 227 97.2% 45 90.5%
74 3.85G 37880930 99.8% 201 99.6% 48 95.7%
76 3.81G 40714262 99.6% 308 98.8% 46 90.1%
78 4.00G 37271824 99.9% 818 99.6% 113 95.7%
87 5.14G 49678042 99.9% 2512 98.4% 426 91.4%
88 4.51G 49024584 99.9% 657 94.1% 205 86.7%
90 5.87G 64179792 99.9% 1027 100.0% 218 96.0%
91 5.49G 48952474 99.9% 3709 100.0% 394 95.4%
92 5.35G 48318194 99.9% 2158 99.6% 358 93.2%
93 4.98G 45098256 99.9% 2689 98.0% 401 95.7%
94 5.31G 47609376 99.9% 2228 100.0% 302 94.7%
95 5.33G 47799930 99.9% 4533 100.0% 570 96.5%
96 4.34G 38893156 99.9% 2326 100.0% 328 95.4%
97 4.62G 41774942 99.9% 1173 99.6% 205 95.6%
98 4.64G 41099162 99.9% 2559 97.2% 243 90.9%
99 4.41G 41545088 99.8% 158 100.0% 41 94.0%
100 4.55G 41198850 99.9% 1818 96.5% 231 88.8%
101 4.08G 36706560 99.9% 3064 99.2% 381 94.7%
102 4.25G 38271362 99.9% 1974 98.0% 280 92.6%
103 4.01G 36258236 99.9% 2374 99.6% 350 95.6%
104 4.32G 39507416 99.9% 2375 100.0% 295 95.8%
105 4.14G 37751412 99.9% 455 98.8% 88 93.9%
106 3.24G 33789398 99.3% 135 100.0% 16 93.6%
107 3.94G 35958628 99.9% 961 98.8% 93 94.7%
108 3.81G 35128618 99.6% 299 99.2% 28 93.3%
110 4.41G 39832638 99.9% 869 99.6% 120 93.8%
111 4.23G 38265164 99.9% 1167 98.8% 184 93.7%
113 4.47G 40114626 99.9% 4699 99.2% 459 94.1%
114 4.15G 37610246 99.9% 1030 98.4% 165 90.2%
115 4.06G 36741122 99.9% 1538 97.6% 316 91.0%
117 5.08G 46050092 99.9% 1876 99.2% 357 91.7%
118 4.61G 40677240 99.8% 991 96.5% 134 89.3%
119 3.57G 32267578 99.9% 1321 98.4% 173 93.8%
120 5.12G 46101768 99.9% 2055 96.9% 283 92.2%
121 5.02G 44891200 99.9% 1063 97.2% 162 92.7%
122 4.35G 38847036 99.9% 2741 96.9% 328 90.2%
123 4.84G 43528842 99.9% 2614 98.8% 358 93.0%
124 5.23G 46709206 99.9% 3116 94.5% 342 88.8%
125 3.44G 31432526 99.9% 1323 99.2% 233 93.3%
127 3.77G 34286630 99.7% 746 94.9% 87 89.0%
128 4.91G 44385696 99.9% 2716 100.0% 401 95.7%
129 5.11G 45898028 99.9% 3621 99.6% 424 94.0%
130 6.52G 58638886 99.9% 3283 99.2% 346 95.5%
131 5.00G 45451438 99.9% 1054 100.0% 161 94.5%
132 4.91G 45782918 99.7% 553 96.5% 59 90.5%
133 4.11G 37079280 100.0% 2798 99.6% 283 94.7%
134 4.19G 37691494 99.9% 1912 99.6% 225 92.8%
135 5.06G 45640186 99.9% 980 93.7% 110 94.0%
136 5.14G 46451684 99.9% 1514 100.0% 199 95.8%
137 5.55G 50133706 99.9% 3069 100.0% 475 97.0%
138 5.17G 46407322 99.9% 1748 97.6% 223 92.8%
139 4.91G 44130552 99.9% 1188 98.8% 188 94.2%
140 4.68G 42457358 99.9% 1024 99.2% 223 93.9%
141 5.37G 48704618 99.9% 2282 100.0% 420 95.9%
142 4.34G 39721426 99.9% 909 100.0% 127.5 94.0%
143 4.04G 36819558 100.0% 1355 99.6% 278.94 94.4%
144 4.20G 39062230 99.9% 748.3 98.0% 115.66 92.7%
145 4.16G 38568320 99.9% 1229 99.2% 211.52 92.9%
146 4.41G 42489920 99.8% 600 97.2% 81.23 89.2%
Table II. Technical parameters in successfully analyzed samples.
ID BRCA Alteration GSscore
2 WT 5.2
4 WT 5.7
5 WT 2.5
6 WT 28.4
8 WT 13.2
9 WT 99.5
10 WT 7.9
11 WT 4.3
12 WT 28.0
13 WT 5.1
14 WT 10.9
15 WT 19.3
16 WT 66.6
17 WT 95.9
18 WT 26.2
19 WT 98.6
20 WT 35.8
21 WT 99.5
22 WT 9.6
23 WT 71.6
24 WT 3.4
25 WT 66.3
26 WT 90.5
27 WT 3.0
28 WT 81.5
29 BRCA1 intron 13 c.4358-31_4358-27del:p.? 3.0
30 WT 34.2
31 WT 21.1
32 WT 84.9
33 WT 3.1
34 WT 95.0
35 WT 79.2
36 WT 72.9
38 WT 9.5
39 WT 3.2
41 BRCA 2 exon 17 c.7887G > A:p.(W2629*):p.(Trp2629Ter) 18.1
42 WT 11.1
43 WT 95.5
45 WT 88.6
46 WT 71.0
47 WT 2.1
48 WT 53.3
49 WT 30.3
50 WT 77.8
51 WT 99.7
53 WT 75.4
54 WT 30.0
57 WT 96.9
58 WT 94.1
59 WT 7.5
61 WT 2.0
62 WT 1.7
70 WT 41.2
73 WT 6.5
74 BRCA2 exon 11 c.5433_5434delinsTT: p.(E1811_E1812delinsD*):p.(Glu1811_Glu1812delinsAspTer) 26.6
76 WT 7.0
78 WT 99.4
87 WT 95.4
88 WT 98.7
90 WT 2.2
91 WT 43.5
92 WT 34.8
93 WT 93.8
94 WT 23.9
95 WT 95.1
96 WT 66.8
97 WT 5.3
98 WT 1.0
99 VUS BRCA1 exon 9 c.964G > A p.Ala322Thr 19,84% 10.0
100 WT 99.7
101 WT 4.0
102 WT 98.8
103 WT 23.3
104 BRCA1 exon 9 c.3229_3229delAG p.Gly1077Ala fs Ter8 95.8
105 WT 6.6
106 BRCA2 exon 23 VUS c.9006A > T; p.Glu3002Asp 4.7
107 WT 21.8
108 WT 0.9
110 WT 13.8
111 WT 72.0
113 WT 93.9
114 WT 25.2
115 WT 99.0
117 WT 98.1
118 WT 99.4
119 WT 35.2
120 WT 23.5
121 WT 75.3
122 WT 64.3
123 WT 99.5
124 WT 94.6
125 VUS BRCA1 exon 23 c.5504G > A, p.R183Q 91.5
127 WT 3.4
128 WT 1.7
129 WT 34.2
130 WT 0.9
131 WT 31.5
132 WT 3.6
133 WT 77.1
134 BRCA2 exon 21 p.A2915Vfs*12:p.Ala2915ValfsTer12 96.7
135 WT 11.0
136 WT 1.4
137 WT 30.3
138 WT 11.0
139 WT 8.5
140 WT 17.4
141 WT 81.0
142 WT 20.5
143 WT 86.2
144 WT 80.8
145 WT 100.0
146 BRCA2 exon 18 c.8184del:p.(K2729Rfs*4):p.(Lys2729ArgfsTer4) 85.7
Abbreviations: BRCA (Breast Related Cancer Antigens); GSS (Genomic Scar Score); VUS (Variants of Uncertain Significance); WT (Wild-Type).
Table III. List of BRCA molecular alterations found in successfully analyzed samples and GSS score evaluation.
Characteristics N = 16
Median age 61.0 (45-82)
ECOG
· 0 13
· 1 3
Primary tumor location
· Ovary 16
· Fallopian tube 0
· Peritoneum 0
FIGO stage
· I-II 1
· III 11
· IV 4
Histological Subtype
· Serous 16
· Endometroid 0
Surgery
· PDS 9
· IDS after 3 cycles 4
· IDS after 6 cycles 3
CRS
· 1 3
· 2 1
· 3 2
· Unknown 1
Residual disease
· R0 12
· R1 2
· R2 2
Serum CA125 level
· Normal 7
· Elevated 9
BRCA1/2 status
· Wild type 15
· BRCA1 1
· BRCA2 0
HRD status
· Positive (GSS > 50) 8
· Negative (GSS < 50) 8
Maintenance therapy
· Bevacizumab 3
· Olaparb 5
· Niraparib 6
· Olaparb + Bevacizumab 1
· None 1
BMI
· < 18.5 1
· 18.5-24.99 7
· 25.0-29.99 3
· ≥30 5
Table IV. Characteristics of the 16 of 147 patients who underwent testing for BRCA1/2 pathogenic alterations and HRD measurement and referred to the Oncology Department of our University Hospital for clinical care.

References

  1. Siegel R, Miller K, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7-34.
  2. Punzón-Jiménez P, Lago V, Domingo S, Simón C, Mas A. Molecular Management of High-Grade Serous Ovarian Carcinoma. Int J Mol Sci. 2022;23.
  3. Tsonis O, Gkrozou F, Vlachos K. Upfront debulking surgery for high-grade serous ovarian carcinoma: current evidence. Ann Transl Med. 2020;8.
  4. Miller D, Blessing J, Krasner C. Phase II evaluation of pemetrexed in the treatment of recurrent or persistent platinum-resistant ovarian or primary peritoneal carcinoma: a study of the Gynecologic Oncology Group. J Clin Oncol. 2009;27:2686-2691.
  5. Moore K, Colombo N, Scambia G. Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2018;379:2495-2505.
  6. Pujade-Lauraine E, Ledermann J, Selle F. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial [published correction appears in Lancet Oncol. 2017;18(9):e510]. Lancet Oncol. 2017;18:1274-1284.
  7. Coleman R, Oza A, Lorusso D. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial [published correction appears in Lancet. 2017;390(10106):1948]. Lancet. 2017;390(10106):1949-1961.
  8. Dann R, DeLoia J, Timms K. BRCA1/2 mutations and expression: response to platinum chemotherapy in patients with advanced stage epithelial ovarian cancer. Gynecol Oncol. 2012;125:677-682.
  9. Ngoi N, Tan D. The role of homologous recombination deficiency testing in ovarian cancer and its clinical implications: do we need it?. ESMO Open. 2021;6.
  10. Wang M, Wu W, Wu W. PARP-1 and Ku compete for repair of DNA double strand breaks by distinct NHEJ pathways. Nucleic Acids Res. 2006;34:6170-6182.
  11. Hoeijmakers J. Genome maintenance mechanisms for preventing cancer. Nature. 2001;411(6835):366-374.
  12. Banerjee S, Moore K, Colombo N. 811MO Maintenance olaparib for patients (pts) with newly diagnosed, advanced ovarian cancer (OC) and a BRCA mutation (BRCAm): 5-year (y) follow-up (f/u) from SOLO1. Ann Oncol. 2020;31:S551-S589.
  13. Oaknin A, Moore K, Colombo N. 4350 e Time to second progression (PFS2) and second subsequent therapy (TSST) for patients (pts) with newly diagnosed, advanced ovarian cancer (OC) and a BRCA mutation (BRCAm) treated with maintenance (mt) olaparib (ola) e Phase III SOLO1 trial. Ann Oncol. 2019;30:v403-v434.
  14. Ray-Coquard I, Pautier P, Pignata S. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med. 2019;381:2416-2428.
  15. Timms K, Mills G, Perry M. Comparison of genomic instability test scores used for predicting PARP activity in ovarian cancer. J Clin Oncol. 2020;38.
  16. Abkevich V, Timms K, Hennessy B. Patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer. Br J Cancer. 2012;107:1776-1782.
  17. Birkbak N, Wang Z, Kim J. Telomeric allelic imbalance indicates defective DNA repair and sensitivity to DNA-damaging agents [published correction appears in Cancer Discov. 2013 Aug;3(8):952]. Cancer Discov. 2012;2:366-375.
  18. Mangogna A, Munari G, Pepe F, Maffii E, Giampaolino P, Ricci G, Fassan M, Malapelle U, Biffi S. Homologous Recombination Deficiency in Ovarian Cancer: from the Biological Rationale to Current Diagnostic Approaches. J Pers Med. 2023;13.
  19. Pepe F, Guerini-Rocco E, Fassan M, Fusco N, Vacirca D, Ranghiero A, Venetis K, Rappa A, Taormina S, Russo G, Rebellato E, Munari G, Moreno-Manuel A, De Angelis C, Zamagni C, Valabrega G, Malapelle U, Troncone G, Barberis M, Iaccarino A. In-house homologous recombination deficiency testing in ovarian cancer: a multi-institutional Italian pilot study. J Clin Pathol. Published online 2023.
  20. Li W, Gao L, Yi X. Patient Assessment and Therapy Planning Based on Homologous Recombination Repair Deficiency. Genomics Proteomics Bioinformatics. Published online 2023.
  21. Leichsenring J, Horak P, Kreutzfeldt S. Variant classification in precision oncology. Int J Cancer. 2019;145:2996-3010.
  22. Malapelle U, Parente P, Pepe F, De Luca C, Cerino P, Covelli C, Balestrieri M, Russo G, Bonfitto A, Pisapia P, Fiordelisi F, D’Armiento M, Bruzzese D, Loupakis F, Pietrantonio F, Triassi M, Fassan M, Troncone G, Graziano P. Impact of Pre-Analytical Factors on MSI Test Accuracy in Mucinous Colorectal Adenocarcinoma: A Multi-Assay Concordance Study. Cells. 2020;9.
  23. Cojocaru E, Parkinson C, Brenton J. Personalising Treatment for High-Grade Serous Ovarian Carcinoma. Clin Oncol (R Coll Radiol). 2018;30:515-524.
  24. Malentacchi F, Ciniselli C, Pazzagli M, Verderio P, Barraud L, Hartmann C, Pizzamiglio S, Weisbuch S, Wyrich R, Gelmini S. Influence of pre-analytical procedures on genomic DNA integrity in blood samples: the SPIDIA experience. Clin Chim Acta. 2015;440:205-10.
Authors

Francesco Pepe - Department of Public Health, Federico II University of Naples, Naples, Italy

Gianluca Russo - Department of Public Health, Federico II University of Naples, Naples, Italy

Amedeo Cefaliello - Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy

Maria Rosaria Lamia - Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy

Roberto Buonaiuto - Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy

Giuseppina Crimaldi - Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy

Claudia Scimone - Department of Public Health, Federico II University of Naples, Naples, Italy

Lucia Palumbo - Department of Public Health, Federico II University of Naples, Naples, Italy

Giuseppina Roscigno - Department of Biology, Federico II University of Naples, Italy

Paola Parente - Pathology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG)

Maria Chiara De Finis - Pathology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG)

Claudia Marchetti - Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy

Pierluigi Giampaolino - Department of Public Health, Federico II University of Naples, Naples, Italy

Carmine De Angelis - Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy

Roberto Bianco - Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy

Giancarlo Troncone - Department of Public Health, Federico II University of Naples, Naples, Italy

Umberto Malapelle - Department of Public Health, Federico II University of Naples, Naples, Italy

How to Cite
Pepe, F., Russo, G., Cefaliello, A., Lamia, M. R., Buonaiuto, R., Crimaldi, G., Scimone, C., Palumbo, L., Roscigno, G., Parente, P., De Finis, M. C. ., Marchetti, C., Giampaolino, P., De Angelis, C. ., Bianco, R., Troncone, G., & Malapelle, U. (2025). Homologous recombination deficiency testing in ovarian cancer: the diagnostic experience of a referral Italian institution. Pathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology, 117(3). https://doi.org/10.32074/1591-951X-1098
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