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Selection of endometrial carcinomas for DNA mismatch repair protein immunohistochemistry using patient age and tumor morphology enhances detection of mismatch repair abnormalities.
Am J Surg Pathol. 2009 Jun; 33(6):925-33.AJ

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 >or=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 >or=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.

Authors+Show Affiliations

Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19238076

Citation

Garg, Karuna, et al. "Selection of Endometrial Carcinomas for DNA Mismatch Repair Protein Immunohistochemistry Using Patient Age and Tumor Morphology Enhances Detection of Mismatch Repair Abnormalities." The American Journal of Surgical Pathology, vol. 33, no. 6, 2009, pp. 925-33.
Garg K, Leitao MM, Kauff ND, et al. Selection of endometrial carcinomas for DNA mismatch repair protein immunohistochemistry using patient age and tumor morphology enhances detection of mismatch repair abnormalities. Am J Surg Pathol. 2009;33(6):925-33.
Garg, K., Leitao, M. M., Kauff, N. D., Hansen, J., Kosarin, K., Shia, J., & Soslow, R. A. (2009). Selection of endometrial carcinomas for DNA mismatch repair protein immunohistochemistry using patient age and tumor morphology enhances detection of mismatch repair abnormalities. The American Journal of Surgical Pathology, 33(6), 925-33. https://doi.org/10.1097/PAS.0b013e318197a046
Garg K, et al. Selection of Endometrial Carcinomas for DNA Mismatch Repair Protein Immunohistochemistry Using Patient Age and Tumor Morphology Enhances Detection of Mismatch Repair Abnormalities. Am J Surg Pathol. 2009;33(6):925-33. PubMed PMID: 19238076.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Selection of endometrial carcinomas for DNA mismatch repair protein immunohistochemistry using patient age and tumor morphology enhances detection of mismatch repair abnormalities. AU - Garg,Karuna, AU - Leitao,Mario M,Jr AU - Kauff,Noah D, AU - Hansen,Jessica, AU - Kosarin,Kristi, AU - Shia,Jinru, AU - Soslow,Robert A, PY - 2009/2/25/entrez PY - 2009/2/25/pubmed PY - 2009/6/24/medline SP - 925 EP - 33 JF - The American journal of surgical pathology JO - Am. J. Surg. Pathol. VL - 33 IS - 6 N2 - 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 >or=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 >or=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. SN - 1532-0979 UR - https://www.unboundmedicine.com/medline/citation/19238076/Selection_of_endometrial_carcinomas_for_DNA_mismatch_repair_protein_immunohistochemistry_using_patient_age_and_tumor_morphology_enhances_detection_of_mismatch_repair_abnormalities_ L2 - http://dx.doi.org/10.1097/PAS.0b013e318197a046 DB - PRIME DP - Unbound Medicine ER -