000			02962nam a22003257a 4500
003			OSt
005			20240305193716.0
008			221010b |||||||| |||| 00| 0 eng d
028			_bPhone: +255 28 298 3384
028			_b Fax: +255 28 298 3386
028			_bEmail: vc@bugando.ac.tz
028			_b Website: www.bugando.ac.tz
040			_cDLC
041			_aEnglish
100			_a Peter F Rambau _922887
245			_aSignificant frequency of MSH2/MSH6 abnormality in ovarian endometrioid carcinoma supports histotype‐specific Lynch syndrome screening in ovarian carcinomas
260			_aMwanza, Tanzania: _bHistopathology & _bCatholic University of Health and Allied Sciences [CUHAS – Bugando] _c22 January 2016
300			_aPages 288-297
490			_vHistopathology Volume 69 Issue 2
520			_a Abstract Aims Lynch syndrome screening in ovarian carcinoma is controversial. The aim of this study was to assess the frequency of deficient mismatch repair (dMMR) protein in a retrospective cohort enriched for non-high-grade serous carcinomas and its association with outcome within histological types. Methods and results Tissue microarrays representing 612 ovarian carcinomas were tested for mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) by immunohistochemistry. dMMR was detected in 13.8% of endometrioid and 2.4% of clear cell carcinomas, but not in other histological types. Within endometrioid carcinomas, 11 of 25 dMMR cases showed abnormal MLH1/PMS2, 10 cases showed abnormal MSH2/MSH6, and four cases showed only abnormal MSH6, indicating that at least 7.7% of endometrioid carcinomas have dMMR probably related to Lynch syndrome. The four dMMR clear cell carcinomas showed abnormal MSH2/MSH6 in three cases and only abnormal MSH6 in one case, all probably related to Lynch syndrome. Within endometrioid carcinomas, dMMR was significantly associated with age <50 years, synchronous endometrial endometrioid carcinoma, a higher CA125 level at diagnosis, higher FIGO grade, absence of ARID1A, and at least 20 CD8-positive intraepithelial lymphocytes per high-power field, but was not associated with cancer-specific death. Age <50 years, higher CA125 levels at diagnosis and at least 20 CD8-positive intraepithelial lymphocytes per high-power field remained significant after adjustment for multiple testing, but their sensitivity for identifying dMMR remained insufficient. Conclusion Our data support the policy of histotype-specific Lynch syndrome screening in ovarian carcinoma confined to endometrioid and clear cell carcinomas.
700			_a Máire A Duggan _944524
700			_aPrafull Ghatage _944415
700			_aKhadija Warfa _944525
700			_a Helen Steed _944495
700			_aRenee Perrier _944526
700			_aLinda E Kelemen _944488
700			_aMartin Köbel _944499
856			_u https://doi.org/10.1111/his.12934 _y https://doi.org/10.1111/his.12934
942			_2ddc _cVM
999			_c19124 _d19124