Selection of endometrial carcinomas for DNA mismatch repair protein immunohistochemistry using patient age and tumor morphology enhances detection of mismatch repair abnormalities Journal Article
| Authors: | Garg, K.; Leitao, M. M. Jr; Kauff, N. D.; Hansen, J.; Kosarin, K.; Shia, J.; Soslow, R. A. |
| Article Title: | Selection of endometrial carcinomas for DNA mismatch repair protein immunohistochemistry using patient age and tumor morphology enhances detection of mismatch repair abnormalities |
| Abstract: | Women with hereditary nonpolyposis colorectal cancer (HNPCC) have a high risk for endometrial cancer (EC) and frequently present with a gynecologic cancer as their first or sentinel malignancy. Identification of these patients is important given their personal and family risk for synchronous and metachronous tumors. The revised Bethesda Guidelines provide screening criteria for HNPCC in colorectal cancers. However, there are currently no such screening recommendations for women with endometrial carcinoma. We applied some of the colorectal cancer screening criteria, including age and tumor morphology, to endometrial endometrioid carcinoma. The purpose of this study was to describe patient and tumor characteristics and to assess the ability of these criteria to enhance detection of mismatch repair (MMR) deficiency, and hence HNPCC in EC. Immunohistochemistry (IHC) for DNA mismatch repair (IHC-MMR) proteins was performed in a defined subset of patients with EC. This included women younger than 50 years of age and women ≤50 years whose tumors showed morphologic features suggestive of MMR deficiency (TM-MMR). The extent of IHC-MMR in the older patient group was compared with that in a comparison group of EC ≤50 years that was previously analyzed for microsatellite instability status. Seventy-one patients met the selection criteria for IHC testing; 32 (45%) showed abnormal results. The rate of IHC abnormality in the younger group was approximately 30% with a nearly equal distribution of MLH1/PMS2 and MSH2/MSH6 abnormalities. In the older age group, TM-MMR triggered IHC analysis in 31 of 34 cases. Of these, 18 cases showed loss of IHC-MMR (58% of cases), 7 with loss of MSH2/MSH6. In contrast, the rate of microsatellite instability in the comparison group was only 21%. The IHC abnormal group showed more frequent tumor infiltrating lymphocytes, dedifferentiated EC, more tumors centered in the lower uterine segment, and more frequent synchronous clear cell carcinomas of the ovary than tumors with a normal immunophenotype. Although many of the patients with loss of IHC-MMR showed personal and/or family history (13 of 32) of HNPCC-associated tumors, most did not. Tumor morphology (TM-MMR) along with IHC-MMR enhances the detection of EC patients at risk of HNPCC. © 2009 by Lippincott Williams & Wilkins. |
| Keywords: | immunohistochemistry; adult; controlled study; human tissue; aged; middle aged; major clinical study; genetics; cancer patient; endometrium carcinoma; endometrial neoplasms; colorectal cancer; tumor associated leukocyte; metabolism; cancer screening; age factors; pathology; morphology; high risk patient; age; colorectal tumor; mismatch repair; microsatellite instability; dna mismatch repair; family history; ovary carcinoma; immunophenotyping; clear cell carcinoma; protein mlh1; endometrial carcinoma; hnpcc; lynch syndrome; mismatch repair protein; protein msh2; protein msh6; endometrium tumor; multiple cancer; colorectal neoplasms, hereditary nonpolyposis; neoplasms, multiple primary |
| Journal Title: | American Journal of Surgical Pathology |
| Volume: | 33 |
| Issue: | 6 |
| ISSN: | 0147-5185 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2009-06-01 |
| Start Page: | 925 |
| End Page: | 933 |
| Language: | English |
| DOI: | 10.1097/PAS.0b013e318197a046 |
| PUBMED: | 19238076 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 9" - "Export Date: 30 November 2010" - "CODEN: AJSPD" - "Source: Scopus" |
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