Tumor BRCA Test for Patients with Epithelial Ovarian Cancer: The Role of Molecular Pathology in the Era of PARP Inhibitor Therapy
Abstract
:1. Introduction
2. Results
2.1. Tumor BRCA Test Performance
2.2. Tumor BRCA1 and BRCA2 Alterations Distribution
2.3. Tumor BRCA1/2 Status According to Clinicopathological Characteristics
2.4. Tumor and Germline BRCA Tests Concordance
2.5. Tumor BRCA Test Workflow in Clinical Diagnostic Setting
3. Discussion
4. Materials and Methods
4.1. Study Population
4.2. Next-Generation Sequencing Analysis of BRCA Status in Tumor Samples
4.3. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Clinicopathological Features | BRCA1 | BRCA2 | ||||
---|---|---|---|---|---|---|
Pathogenic/Likely Pathogenic Mutations | VUS | WT | Pathogenic/Likely Pathogenic Mutations | VUS | WT | |
Tumor Site | ||||||
Primary tumors (n = 200) | 46 (23.0%) | 13 (6.5%) | 141 (70.5%) | 14 (7.0%) | 7 (3.5%) | 179 (89.5%) |
Metastases/Recurrences (n = 21) | 1 (4.8%) | 3 (14.3%) | 17 (81.0%) | 1 (4.8%) | 2 (9.5%) | 18 (85.7%) |
Histologycal Subtype | ||||||
High-grade serous carcinoma (n = 194) | 47 (24.2%) | 16 (8.2%) | 131 (67.5%) | 14 (7.2%) | 7 (3.6%) | 173 (89.2%) |
Non-serous carcinoma/subtype not defined (n = 27) | 0 | 0 | 27 (100%) | 1 (3.7%) | 2 (7.4%) | 24 (88.9%) |
Pathological Staging | ||||||
T1 (n = 15) | 2 (13.3%) | 0 | 13 (86.7%) | 2 (13.3%) | 2 (13.3%) | 11 (73.3%) |
T2 (n = 29) | 6 (20.7%) | 1 (3.4%) | 22 (75.9%) | 3 (10.3%) | 0 | 26 (89.7%) |
T3 (n = 116) | 25 (21.6%) | 8 (6.9%) | 83 (71.6%) | 4 (3.4%) | 3 (2.6%) | 109 (94.0%) |
NA (n = 61) | 14 (23.0%) | 7 (11.5%) | 40 (65.6%) | 6 (9.8%) | 4 (6.6%) | 51 (83.6%) |
N0 (n = 39) | 5 (12.8%) | 0 | 34 (87.2%) | 3 (7.7%) | 4 (10.3%) | 32 (82.1%) |
N1 (n = 65) | 18 (2.7%) | 6 (9.2%) | 41 (63.1%) | 2 (3.1%) | 1 (1.5%) | 62 (95.4%) |
NX (n = 56) | 10 (17.9%) | 3 (5.4%) | 43 (76.8%) | 4 (7.1%) | 0 | 52 (92.9%) |
NA (n = 61) | 14 (23.0%) | 7 (11.5%) | 40 (65.6%) | 6 (9.8%) | 4 (6.6%) | 51 (83.6%) |
Family History | ||||||
Positive (n = 93) | 24 (25.8%) | 8 (8.6%) | 61 (65.6%) | 7 (7.5%) | 6 (6.5%) | 80 (86.0%) |
Negative (n = 101) | 16 (15.8%) | 7 (6.9%) | 78 (77.2%) | 7 (6.9%) | 2 (2.0%) | 92 (91.1%) |
NA (n = 27) | 7 (25.9%) | 1 (3.7%) | 19 (70.4%) | 1 (3.7%) | 1 (3.7%) | 25 (92.6%) |
Time of Test Request | ||||||
At pathological diagnosis (n = 123) | 28 (22.8%) | 8 (6.5%) | 87 (70.7%) | 8 (6.5%) | 5 (4.1%) | 110 (89.4%) |
At least 6 months after pathological diagnosis without relapse (n = 35) | 9 (25.7%) | 2 (5.7%) | 24 (68.6%) | 3 (8.6%) | 3 (8.6%) | 29 (82.9%) |
At relapse (n = 37) | 4 (10.8%) | 5 (13.5%) | 28 (75.7%) | 2 (5.4%) | 1 (2.7%) | 34 (91.9%) |
NA (n = 26) | 6 (23.1%) | 1 (3.8%) | 19 (73.1%) | 2 (7.7%) | 0 | 24 (92.3%) |
Clinicopathological Features | BRCA MUTATED (Phatogenic/Likely Pathogenic Mutations) | BRCA WT * | p Value ** |
---|---|---|---|
Tumor Site | |||
Primary tumors (n = 200) | 62 (31.0%) | 138 (69.0%) | 0.07 |
Metastases/Recurrences (n = 21) | 2 (9.5%) | 19 (90.5%) | |
Histologycal Subtype | |||
High-grade serous carcinoma (n = 194) | 61 (31.4%) | 133 (68.6%) | 0.005 |
Non-serous carcinoma/subtype not defined (n = 27) | 1 (3.7%) | 26 (96.3%) | |
Pathological Staging | |||
T1 (n = 15) | 4 (26.7%) | 11 (73.3%) | 0.716 |
T2 (n = 29) | 9 (31.0%) | 20 (69.0%) | |
T3 (n = 116) | 29 (25.0%) | 87 (75.0%) | |
NA (n = 61) | 20 (32.8%) | 41 (67.2%) | |
N0 (n = 39) | 8 (20.5%) | 31 (79.5%) | 0.518 |
N1 (n = 65) | 20 (30.8%) | 45 (69.2%) | |
NX (n = 56) | 14 (25.0%) | 42 (75.0%) | |
NA (n = 61) | 20 (32.8%) | 41 (67.2%) | |
Family History | |||
Positive (n = 93) | 31 (33.3%) | 62 (66.7%) | 0.258 |
Negative (n = 101) | 23 (22.8%) | 78 (77.2%) | |
NA (n = 27) | 8 (29.6%) | 19 (70.4%) | |
Time of Test Request | |||
At pathological diagnosis (n = 123) | 36 (29.3%) | 87 (70.7%) | 0.33 |
At least 6 months after pathological diagnosis without relapse (n = 35) | 12 (34.3%) | 23 (65.7%) | |
At relapse (n = 37) | 6 (16.2%) | 31 (83.8%) | |
NA (n = 26) | 8 (30.8%) | 18 (69.2%) |
Tumor BRCA Test | Germline BRCA Test | |||
---|---|---|---|---|
Positive | Negative | |||
Pathogenic/Likely Pathogenic | VUS | |||
Positive | Pathogenic/Likely Pathogenic | 18 (78.3%) | / | 5 (21.7%) |
VUS | / | 2 (40%) | 3 (60%) | |
Negative | / | / | 34 (100%) |
Clinicopathological Features | n (%) |
---|---|
Time of Test Request | |
At pathological diagnosis | 123 (55.2%) |
At least 6 months after pathological diagnosis without relapse | 35 (15.7%) |
At relapse | 37 (16.6%) |
NA | 28 (12.6%) |
Histological Subtype | |
High-grade serous carcinoma | 195 (87.4%) |
Endometroid carcinoma | 16 (7.2%) |
Clear cell carcinoma | 9 (4%) |
Carcinoma—subtype not defined | 3 (1.3%) |
TN Pathological Staging | |
T1 | 15 (6.7%) |
T2 | 29 (13%) |
T3 | 116 (52%) |
NA | 63 (28.3%) |
N0 | 39 (17.5%) |
N1 | 65 (29.1%) |
NX | 56 (25.1%) |
NA | 63 (28.3%) |
Specimen Analyzed | |
Primary Tumor | 201 (90.1%) |
Ovary localization | 169 (75.8%) |
Extra-ovary localization | 32 (14.3%) |
Pelvic localization | 14 (43.8%) |
Extra-Pelvic localization | 12 (37.5%) |
NA | 6 (18.7%) |
Metastasis/recurrence | 22 (9.9%) |
Lymph nodal metastasis | 3 (13.6%) |
Extra lymph nodal metastasis | 19 (86.4%) |
Neoadjuvant Treatment | |
Yes | 46 (20.6%) |
No | 114 (51.1%) |
NA | 63 (28.3%) |
Surgery | |
R0 - no residual disease | 135 (60.5%) |
R+ < 1 cm | 42 (18.8%) |
R+ > 1 cm | 19 (8.5%) |
NA | 27 (12.1%) |
Family History | |
Positive | 93 (41.7%) |
Negative | 101 (45.3%) |
NA | 29 (13%) |
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Fumagalli, C.; Tomao, F.; Betella, I.; Rappa, A.; Calvello, M.; Bonanni, B.; Bernard, L.; Peccatori, F.; Colombo, N.; Viale, G.; et al. Tumor BRCA Test for Patients with Epithelial Ovarian Cancer: The Role of Molecular Pathology in the Era of PARP Inhibitor Therapy. Cancers 2019, 11, 1641. https://doi.org/10.3390/cancers11111641
Fumagalli C, Tomao F, Betella I, Rappa A, Calvello M, Bonanni B, Bernard L, Peccatori F, Colombo N, Viale G, et al. Tumor BRCA Test for Patients with Epithelial Ovarian Cancer: The Role of Molecular Pathology in the Era of PARP Inhibitor Therapy. Cancers. 2019; 11(11):1641. https://doi.org/10.3390/cancers11111641
Chicago/Turabian StyleFumagalli, Caterina, Federica Tomao, Ilaria Betella, Alessandra Rappa, Mariarosaria Calvello, Bernardo Bonanni, Loris Bernard, Fedro Peccatori, Nicoletta Colombo, Giuseppe Viale, and et al. 2019. "Tumor BRCA Test for Patients with Epithelial Ovarian Cancer: The Role of Molecular Pathology in the Era of PARP Inhibitor Therapy" Cancers 11, no. 11: 1641. https://doi.org/10.3390/cancers11111641