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Morphologic patterns associated with BRCA1 and BRCA2 genotype in ovarian carcinoma.

Publication ,  Journal Article
Soslow, RA; Han, G; Park, KJ; Garg, K; Olvera, N; Spriggs, DR; Kauff, ND; Levine, DA
Published in: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
April 2012

This study was undertaken with the hypothesis that certain common morphologic features of ovarian carcinomas are predictably associated with BRCA1 and BRCA2 deficiencies. We selected 43 high-grade serous carcinomas diagnosed at Memorial Sloan-Kettering Cancer Center that were studied as part of The Cancer Genome Atlas pilot project. In addition to 12 randomly selected nonfamilial BRCA-unassociated cases, all 31 Memorial Sloan-Kettering Cancer Center cases with BRCA1 or BRCA2 abnormality were included (n=43). Slides were examined to assess tumor architecture, mitotic index, tumor-infiltrating lymphocytes (TILs), nuclear pleomorphism, necrosis, and involvement of fallopian tube epithelium. Comparing BRCA1-associated cases (BRCA1 germline mutation, n=4, BRCA1 somatic mutation, n=6, BRCA1 promoter methylation, n=13) with unassociated cases (n=12) identified statistically significant differences in morphology. BRCA1-associated high-grade serous carcinomas had more frequent Solid, pseudoEndometrioid, and Transitional cell carcinoma-like morphology (SET features) (P=0.0045), higher mitotic indexes (P=0.012), more TILs (P=0.034), and either geographic or comedo necrosis (P=0.034). BRCA2-associated cases (germline mutation, n=4 and somatic mutation, n=4) tended to show SET features, but they were relatively deficient in TILs and necrosis. Two algorithms incorporating tumor architecture, necrosis, and either mitotic indexes or TILs separated cases that showed 2 of 3 features (BRCA1 associated) from those with 0 of 3 features (BRCA unassociated; P=0.0016 and P=0.0033). A test set comprising 9 BRCA1 germline mutants and 14 high-grade serous carcinoma controls lacking BRCA1 and BRCA2 germline mutation was used to validate the algorithms, with specific emphasis on the ability to detect cases with BRCA1 germline mutation. Best results were obtained with the algorithm that incorporated SET features, necrosis, and mitotic index (P=0.0072; sensitivity of 1.0 (95% CI, 0.66-1.0); specificity of 0.57 (95% CI, 0.29-0.82); positive predictive value of 0.60 (95% CI, 0.32-0.84) and a negative predictive value of 1.0 (95% CI, 0.63-1.0)). These preliminary data indicate potential strong associations between morphology and genotype in high-grade serous carcinomas.

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Published In

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

DOI

EISSN

1530-0285

ISSN

0893-3952

Publication Date

April 2012

Volume

25

Issue

4

Start / End Page

625 / 636

Related Subject Headings

  • Promoter Regions, Genetic
  • Prognosis
  • Predictive Value of Tests
  • Phenotype
  • Pathology
  • Ovarian Neoplasms
  • New York City
  • Neoplasm Grading
  • Necrosis
  • Mutation
 

Citation

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MLA
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Soslow, R. A., Han, G., Park, K. J., Garg, K., Olvera, N., Spriggs, D. R., … Levine, D. A. (2012). Morphologic patterns associated with BRCA1 and BRCA2 genotype in ovarian carcinoma. Modern Pathology : An Official Journal of the United States and Canadian Academy of Pathology, Inc, 25(4), 625–636. https://doi.org/10.1038/modpathol.2011.183
Soslow, Robert A., Guangming Han, Kay J. Park, Karuna Garg, Narciso Olvera, David R. Spriggs, Noah D. Kauff, and Douglas A. Levine. “Morphologic patterns associated with BRCA1 and BRCA2 genotype in ovarian carcinoma.Modern Pathology : An Official Journal of the United States and Canadian Academy of Pathology, Inc 25, no. 4 (April 2012): 625–36. https://doi.org/10.1038/modpathol.2011.183.
Soslow RA, Han G, Park KJ, Garg K, Olvera N, Spriggs DR, et al. Morphologic patterns associated with BRCA1 and BRCA2 genotype in ovarian carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2012 Apr;25(4):625–36.
Soslow, Robert A., et al. “Morphologic patterns associated with BRCA1 and BRCA2 genotype in ovarian carcinoma.Modern Pathology : An Official Journal of the United States and Canadian Academy of Pathology, Inc, vol. 25, no. 4, Apr. 2012, pp. 625–36. Epmc, doi:10.1038/modpathol.2011.183.
Soslow RA, Han G, Park KJ, Garg K, Olvera N, Spriggs DR, Kauff ND, Levine DA. Morphologic patterns associated with BRCA1 and BRCA2 genotype in ovarian carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2012 Apr;25(4):625–636.

Published In

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

DOI

EISSN

1530-0285

ISSN

0893-3952

Publication Date

April 2012

Volume

25

Issue

4

Start / End Page

625 / 636

Related Subject Headings

  • Promoter Regions, Genetic
  • Prognosis
  • Predictive Value of Tests
  • Phenotype
  • Pathology
  • Ovarian Neoplasms
  • New York City
  • Neoplasm Grading
  • Necrosis
  • Mutation