Endometrial carcinomas in women aged 40 years and younger: Tumors associated with loss of DNA mismatch repair proteins comprise a distinct clinicopathologic subset Journal Article
| Authors: | Garg, K.; Shih, K.; Barakat, R.; Zhou, Q.; Iasonos, A.; Soslow, R. A. |
| Article Title: | Endometrial carcinomas in women aged 40 years and younger: Tumors associated with loss of DNA mismatch repair proteins comprise a distinct clinicopathologic subset |
| Abstract: | Endometrial carcinomas (ECs) in young women (≤40y) are usually managed conservatively in selected patients. Whether oophorectomy with total hysterectomy is mandated for patients failing hormonal therapy is controversial. Recognition of features that might discourage conservative management and ovarian preservation are currently poorly characterized. We evaluated these patients for DNA mismatch repair (MMR) protein defects to assess whether the MMR status had an impact on therapeutic decision making. Seventy ECs in women of 40 years of age or younger (n=70) were identified from review of institutional databases (1993-present). All available slides were reviewed and DNA MMR immunohistochemistry was performed using 4 markers (MLH1, PMS2, MSH2, and MSH6) in cases with available blocks (n=54). ECs were predominantly endometrioid (65/70), and most were low grade (1988 International Federation of Gynecology and Obstetrics grades 1 or 2, 83%). Five (7%) were undifferentiated carcinomas. Most patients presented at early stage (stages I to II, 90%). A significant number of patients also had synchronous ovarian carcinomas (9 of 70, 13%), predominantly endometrioid (7 of 9), whereas 2 were ovarian clear cell carcinomas. Sixty-six of the 70 patients are alive with no evidence of disease, whereas 4 patients (6%) died of disease. Immunohistochemistry for DNA MMR showed loss of at least 1 protein in 9 of 54 cases (16%) with slight predominance of MSH2/MSH6 abnormalities (5 of 9) compared with loss of MLH1/PMS2. Tumors with MMR loss frequently occurred in women with low body mass index; these tumors were of higher grade and associated with worse clinical outcomes. They frequently showed tumor characteristics associated with microsatellite instability, including tumor infiltrating lymphocytes, undifferentiated or dedifferentiated histology, and lower uterine segment origin. These tumors also showed lower estrogen receptor/progesterone receptor expression compared with tumors with retained staining for MMR proteins. None of the cases with synchronous ovarian and endometrial endometrioid carcinomas showed loss of MMR proteins, whereas 1 of 2 ECs with synchronous CCC of ovary showed loss of MSH2/MSH6.As young women with endometrioid carcinomas who show loss of mismatch proteins are at risk for high-grade tumors with worse clinical outcomes and lower estrogen receptor/progesterone receptor expression, they may not be appropriate candidates for conservative management. Although young EC patients are at increased risk for synchronous endometrioid ovarian carcinomas, this does not seem to be associated with MMR loss. © 2009 by Lippincott Williams & Wilkins. |
| Keywords: | immunohistochemistry; adult; treatment outcome; young adult; dna binding protein; genetics; dna-binding proteins; mortality; patient selection; cancer staging; endometrioid carcinoma; endometrial neoplasms; neoplasm staging; adenocarcinoma; ovarian neoplasms; nuclear protein; down-regulation; risk factors; age factors; enzymology; pathology; risk factor; biopsy; time; time factors; age; risk assessment; nuclear proteins; mismatch repair; dna mismatch repair; ovary tumor; adaptor proteins, signal transducing; dna repair enzymes; down regulation; adenocarcinoma, clear cell; polydeoxyribonucleotide synthase; adenosine triphosphatase; signal transducing adaptor protein; mlh1 protein, human; endometrial carcinoma; protein msh2; endometrium tumor; multiple cancer; neoplasms, multiple primary; hnpcc/lynch syndrome; young patients; g t mismatch binding protein; g-t mismatch-binding protein; msh2 protein, human; pms2 protein, human; adenosine triphosphatases; carcinoma, endometrioid; muts homolog 2 protein |
| Journal Title: | American Journal of Surgical Pathology |
| Volume: | 33 |
| Issue: | 12 |
| ISSN: | 0147-5185 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2009-12-01 |
| Start Page: | 1869 |
| End Page: | 1877 |
| Language: | English |
| DOI: | 10.1097/PAS.0b013e3181bc9866 |
| PUBMED: | 19898223 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 30 November 2010" - "CODEN: AJSPD" - "Source: Scopus" |
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