OBJECTIVE: It is believed that 24-40% of ovarian cancers have dysfunction in the BRCA1 or BRCA2 (BRCAness) genes, due to either inherited or somatic mutations or due to epigenetic inactivation. Demonstration of ovarian cancers with BRCAness is becoming important both due to the possibility of offering genetic counseling and due to beneficial effects of polyadenosine diphosphate ribose polymerase inhibitor treatment in this group. As DNA sequencing is expensive and time consuming, efforts have been devoted to develop more indirect methods for BRCA screening that can improve the selection of patients for sequence-based BRCA testing. DESIGN: BRCA1 immunohistochemistry, fluorescence in situ hybridization (FISH) and methylation analyses were performed on formalin-fixed, paraffin-embedded ovarian cancer tissue. SAMPLE: Fifty-four ovarian cancers; 15 BRCA1 cancers, four BRCA2 cancers, 10 cancers from patients with a family history but no mutation detected, and 25 ovarian cancers with unknown BRCA1 status. RESULTS: Abnormal BRCA1 immunohistochemistry was found to indicate BRCA mutations with a sensitivity of 80%, a specificity of 93% and an estimated positive predictive value of 73%. The FISH analyses supported the diagnosis in most cases. Methylation analyses could indicate BRCA deficiency in combination with one of the other methods. CONCLUSIONS: BRCA1 immunohistochemistry is a promising screening method for BRCA1 mutation detection.
OBJECTIVE: It is believed that 24-40% of ovarian cancers have dysfunction in the BRCA1 or BRCA2 (BRCAness) genes, due to either inherited or somatic mutations or due to epigenetic inactivation. Demonstration of ovarian cancers with BRCAness is becoming important both due to the possibility of offering genetic counseling and due to beneficial effects of polyadenosine diphosphate ribose polymerase inhibitor treatment in this group. As DNA sequencing is expensive and time consuming, efforts have been devoted to develop more indirect methods for BRCA screening that can improve the selection of patients for sequence-based BRCA testing. DESIGN:BRCA1 immunohistochemistry, fluorescence in situ hybridization (FISH) and methylation analyses were performed on formalin-fixed, paraffin-embedded ovarian cancer tissue. SAMPLE: Fifty-four ovarian cancers; 15 BRCA1 cancers, four BRCA2cancers, 10 cancers from patients with a family history but no mutation detected, and 25 ovarian cancers with unknown BRCA1 status. RESULTS: Abnormal BRCA1 immunohistochemistry was found to indicate BRCA mutations with a sensitivity of 80%, a specificity of 93% and an estimated positive predictive value of 73%. The FISH analyses supported the diagnosis in most cases. Methylation analyses could indicate BRCA deficiency in combination with one of the other methods. CONCLUSIONS:BRCA1 immunohistochemistry is a promising screening method for BRCA1 mutation detection.
Authors: Karuna Garg; Douglas A Levine; Narciso Olvera; Fanny Dao; Maria Bisogna; Angeles Alvarez Secord; Andrew Berchuck; Ethan Cerami; Nikolaus Schultz; Robert A Soslow Journal: Am J Surg Pathol Date: 2013-01 Impact factor: 6.394
Authors: J L Meisel; D M Hyman; K Garg; Q Zhou; F Dao; M Bisogna; J Gao; N D Schultz; R N Grisham; M Phillips; A Iasonos; N D Kauff; D A Levine; R A Soslow; D R Spriggs Journal: Ann Oncol Date: 2014-10-03 Impact factor: 32.976
Authors: E Sun Paik; Chi-Son Chang; Ye Lin Chae; So Young Oh; Sun-Ju Byeon; Chul Jung Kim; Yoo-Young Lee; Tae-Joong Kim; Jeong-Won Lee; Byoung-Gie Kim; Chel Hun Choi Journal: Front Oncol Date: 2021-11-08 Impact factor: 6.244