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Morphologic correlates of molecular alterations in extrauterine Müllerian carcinomas.

Publication ,  Journal Article
Ritterhouse, LL; Nowak, JA; Strickland, KC; Garcia, EP; Jia, Y; Lindeman, NI; Macconaill, LE; Konstantinopoulos, PA; Matulonis, UA; Liu, J ...
Published in: Mod Pathol
August 2016

Extrauterine high-grade serous carcinomas can exhibit various histologic patterns including (1) classic architecture that is papillary, micropapillary and infiltrative and (2) solid, endometrioid, and transitional (ie, SET) patterns. Although the SET pattern has been associated with germline BRCA mutations, potential molecular underpinnings have not been fully investigated. DNA was isolated from 174 carcinomas of the fallopian tube, ovary, or peritoneum. Targeted next-generation sequencing was performed and single-nucleotide and copy number variants were correlated with morphologic subtype. Overall, 79% of tumors were classified as high-grade serous carcinoma (n=138), and the most common mutations in high-grade serous carcinomas were TP53 (94%), BRCA1 (25%), BRCA2 (11%), and ATM (7%). Among chemotherapy-naive high-grade serous carcinomas, 40 cases exhibited classic morphology and 40 cases had non-classic morphology (SET or ambiguous features). Mutations in homologous recombination pathways were seen across all tumor histotypes. High-grade serous carcinomas with homologous recombination mutations were six times more likely to be associated with non-classic histology (P=0.002) and were significantly more likely to be platinum sensitive and have improved progression-free survival (PFS) (P=0.007 and P=0.004, respectively). In a multivariate analysis adjusted for age, homologous recombination mutation status and increased copy number variants were independently associated with improved PFS (P=0.008 and P=0.005, respectively). These findings underscore the potential significance of variant morphologic patterns and comprehensive genomic analysis in high-grade serous carcinomas with potential implications for pathogenesis, as well as response to targeted therapies.

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Published In

Mod Pathol

DOI

EISSN

1530-0285

Publication Date

August 2016

Volume

29

Issue

8

Start / End Page

893 / 903

Location

United States

Related Subject Headings

  • Risk Factors
  • Proportional Hazards Models
  • Phenotype
  • Peritoneal Neoplasms
  • Pathology
  • Ovarian Neoplasms
  • Neoplasms, Cystic, Mucinous, and Serous
  • Neoplasm Grading
  • Mutation
  • Multivariate Analysis
 

Citation

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Ritterhouse, L. L., Nowak, J. A., Strickland, K. C., Garcia, E. P., Jia, Y., Lindeman, N. I., … Howitt, B. E. (2016). Morphologic correlates of molecular alterations in extrauterine Müllerian carcinomas. Mod Pathol, 29(8), 893–903. https://doi.org/10.1038/modpathol.2016.82
Ritterhouse, Lauren L., Jonathan A. Nowak, Kyle C. Strickland, Elizabeth P. Garcia, Yonghui Jia, Neal I. Lindeman, Laura E. Macconaill, et al. “Morphologic correlates of molecular alterations in extrauterine Müllerian carcinomas.Mod Pathol 29, no. 8 (August 2016): 893–903. https://doi.org/10.1038/modpathol.2016.82.
Ritterhouse LL, Nowak JA, Strickland KC, Garcia EP, Jia Y, Lindeman NI, et al. Morphologic correlates of molecular alterations in extrauterine Müllerian carcinomas. Mod Pathol. 2016 Aug;29(8):893–903.
Ritterhouse, Lauren L., et al. “Morphologic correlates of molecular alterations in extrauterine Müllerian carcinomas.Mod Pathol, vol. 29, no. 8, Aug. 2016, pp. 893–903. Pubmed, doi:10.1038/modpathol.2016.82.
Ritterhouse LL, Nowak JA, Strickland KC, Garcia EP, Jia Y, Lindeman NI, Macconaill LE, Konstantinopoulos PA, Matulonis UA, Liu J, Berkowitz RS, Nucci MR, Crum CP, Sholl LM, Howitt BE. Morphologic correlates of molecular alterations in extrauterine Müllerian carcinomas. Mod Pathol. 2016 Aug;29(8):893–903.

Published In

Mod Pathol

DOI

EISSN

1530-0285

Publication Date

August 2016

Volume

29

Issue

8

Start / End Page

893 / 903

Location

United States

Related Subject Headings

  • Risk Factors
  • Proportional Hazards Models
  • Phenotype
  • Peritoneal Neoplasms
  • Pathology
  • Ovarian Neoplasms
  • Neoplasms, Cystic, Mucinous, and Serous
  • Neoplasm Grading
  • Mutation
  • Multivariate Analysis