Ovarian endometrioid adenocarcinoma: Incidence and clinical significance of the morphologic and immunohistochemical markers of mismatch repair protein defects and tumor microsatellite instability

Anil Aysal, Anthony Karnezis, Irum Medhi, James P. Grenert, Charles J. Zaloudek, Joseph T. Rabban

Research output: Contribution to journalArticle

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Abstract

A subset of women with uterine cancer exhibiting defective mismatch repair (MMR) proteins and microsatellite instability (MSI) may have Lynch syndrome, which also confers a risk for colorectal cancer and other cancers in the patient and in her family. Screening algorithms based on clinical and pathologic criteria are effective in determining which patients with uterine cancer are most likely to benefit from definitive genetic testing for Lynch syndrome. Ovarian cancer, particularly endometrioid adenocarcinoma, is also associated with Lynch syndrome, although the risk is much smaller than for uterine cancer. This study evaluated whether the morphologic criteria [tumor-infiltrating lymphocytes (TILs), peritumoral lymphocytes (PTLs), dedifferentiated morphology)] currently used to screen uterine cancer for further Lynch syndrome testing can be applied to ovarian cancer. Among 71 patients with pure ovarian endometrioid adenocarcinoma treated at a single institution, 13% had a tumor with TILs, 3% had PTLs, and none had dedifferentiated morphology. Overall, 10% of tumors had abnormal MMR protein status, defined as complete immunohistochemical loss of expression of MLH1, MSH2, MSH6, and/ or PMS2. Each of these tumors with abnormal MMR status demonstrated MSI using a polymerase chain reaction-based assay evaluating 5 mononucleotide repeat markers. No relationship was found between patient age, TILs, PTLs, or a spectrum of other morphologic variables and MMR protein status/MSI. Only 1/7 tumors with abnormal MMR/MSI had TILs/PTLs. Among 14 patients who died, 12 (86%) had normal MMR status. Among 7 patients with tumors with abnormal MMR/ MSI, 5 (71%) were alive without disease. Concurrent uterine tumor was present in 5/7 patients whose ovarian tumor had abnormal MMR/MSI. This study suggests that the morphologic criteria used to screen patients with uterine cancer for further Lynch syndrome testing are not applicable in patients with ovarian cancer. Although abnormal MMR/MSI did not carry prognostic value in this study, it did predict the involvement of the uterus by the tumor. Thus, in patients with ovarian endometrioid adenocarcinoma who undergo uterus-sparing surgery, abnormal MMR/MSI should prompt further diagnostic evaluation of the endometrium for tumor.

Original languageEnglish (US)
Pages (from-to)163-172
Number of pages10
JournalAmerican Journal of Surgical Pathology
Volume36
Issue number2
DOIs
StatePublished - Feb 1 2012
Externally publishedYes

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Endometrioid Carcinoma
Microsatellite Instability
DNA Mismatch Repair
Hereditary Nonpolyposis Colorectal Neoplasms
Uterine Neoplasms
Incidence
Tumor-Infiltrating Lymphocytes
Neoplasms
Proteins
Lymphocytes
Ovarian Neoplasms
Uterus
Genetic Testing
Endometrium
Colorectal Neoplasms

Keywords

  • Lynch syndrome
  • Microsatellite instability
  • Mismatch repair proteins
  • Ovarian cancer
  • Tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

Cite this

Ovarian endometrioid adenocarcinoma : Incidence and clinical significance of the morphologic and immunohistochemical markers of mismatch repair protein defects and tumor microsatellite instability. / Aysal, Anil; Karnezis, Anthony; Medhi, Irum; Grenert, James P.; Zaloudek, Charles J.; Rabban, Joseph T.

In: American Journal of Surgical Pathology, Vol. 36, No. 2, 01.02.2012, p. 163-172.

Research output: Contribution to journalArticle

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