Towards identification of hereditary DNA mismatch repair deficiency: Sebaceous neoplasm warrants routine immunohistochemical screening regardless of patient's age or other clinical characteristics Journal Article

  

Authors:	Orta, L.; Klimstra, D. S.; Qin, J.; Mecca, P.; Tang, L. H.; Busam, K. J.; Shia, J.
Article Title:	Towards identification of hereditary DNA mismatch repair deficiency: Sebaceous neoplasm warrants routine immunohistochemical screening regardless of patient's age or other clinical characteristics
Abstract:	Although the significance of immunohistochemical detection of DNA mismatch repair proteins and/or microsatellite instability testing in identifying patients at risk for germline deficiency in DNA mismatch repair genes is well established in colorectal carcinomas, the proper use of such techniques in sebaceous neoplasms, another tumor type that has been implicated in patients with hereditary DNA mismatch repair deficiency, has not been clearly defined. In this study, we stratified a series of 27 patients with 1 or more sebaceous neoplasms based on the pattern of immunohistochemical expression of MLH1, MSH2, MSH6, and PMS2, and comparatively analyzed their clinical and pathologic characteristics, including tumor-infiltrating lymphocytes and peritumoral lymphocytic response as determined by immunohistochemical staining for CD3. The study tissue samples included 30 sebaceous carcinomas, 14 sebaceous adenomas, and 7 sebaceous hyperplasias, along with 8 concurrent nonsebaceous lesions from 6 patients. Overall, 12 of the 27 (44%) patients showed abnormal IHC staining with mismatch repair proteins in their sebaceous tumors, the most commonly seen abnormality being concurrent loss of MSH2 and MSH6 (8/12, 67%). Sebaceous adenomas and carcinomas occurring in the same patients showed an identical staining pattern, as did hereditary nonpolyposis colorectal cancer-related nonsebaceous tumors in the same patients. When compared with cases that had normal expression of the mismatch repair proteins, cases with abnormal expression tended to be younger (median age, 56.5y vs. 68y), more likely to involve sites outside the head and neck (9/12 vs. 0/15), and more likely to have synchronous or metachronous visceral malignancies (8/12 vs. 3/15) and a positive family history. Furthermore, sebaceous tumors with abnormal expression had significantly higher CD3-positive tumor-infiltrating lymphocytes and peritumoral lymphocytic response. Thus, all these factors (age less than 60y, involvement of nonhead and neck sites, visceral malignancy, family history fulfilling at least Bethesda guidelines, and lymphocytic infiltration) bore informative value in predicting abnormal expression of DNA mismatch repair proteins. However, their sensitivity was only modest, being 58%, 75%, 67%, 78%, and 75%, respectively. On such a premise, given that sebaceous neoplasms are only infrequently encountered, and that immunohistochemistry is easily available and reasonably reliable, we recommend that, when there exists a desire to identify hereditary DNA mismatch repair deficiency, routine immunohistochemical detection of DNA mismatch repair proteins be performed in all sebaceous neoplasms regardless of patient's age or other clinical characteristics. © 2009 by Lippincott Williams & Wilkins.
Keywords:	immunohistochemistry; adult; clinical article; controlled study; human tissue; protein expression; aged; aged, 80 and over; middle aged; genetics; clinical feature; histopathology; sensitivity and specificity; colorectal cancer; adenocarcinoma; cd3 antigen; tumor associated leukocyte; antigens, cd3; lymphocytes, tumor-infiltrating; metabolism; tumor localization; age factors; age; biosynthesis; immunology; screening; colorectal tumor; mismatch repair; microsatellite instability; dna mismatch repair; family history; reliability; genetic disorder; protein mlh1; mismatch repair protein; protein msh2; protein msh6; colorectal neoplasms, hereditary nonpolyposis; mismatch repair protein pms2; hereditary nonpolyposis colorectal cancer; muir-torre syndrome; sebaceous adenoma; sebaceous carcinoma; dna mismatch repair deficiency; sebaceous gland adenoma; sebaceous gland tumor; adenocarcinoma, sebaceous
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:	934
End Page:	944
Language:	English
DOI:	10.1097/PAS.0b013e318199edca
PUBMED:	19342947
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-67549086705&partnerID=40&md5=59a104f7d4194f60ea9c2c1775bb6775
Notes:	--- - "Cited By (since 1996): 5" - "Export Date: 30 November 2010" - "CODEN: AJSPD" - "Source: Scopus"

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