Differences in Mismatch Repair Protein Expression of Cervical Adenocarcinoma and Carcinoma of the Lower Uterine Segment
Birgit Helmchen, Regine Brand, Michael Kurrer, Paul Komminoth, Peter Sinn. Stadtspital Triemli, Zürich, Switzerland; University of Heidelberg, Heidelberg, Germany; Enge Institute of Pathology, Zurich, Switzerland
Background: Carcinomas of the lower uterine segment (LUS) with prominent cervical involvement need to be distinguished from primary cervical adenocarcinoma (PCAC) because of differences in behavior and treatment. Furthermore, an association of carcinoma arising in the LUS with impaired DNA mismatch repair protein (MMRP) expression predictive for Lynch syndrome has been described, while MMRP expression in PCAC is not well characterized.
Design: H&E slides and pathological reports from 42 hysterectomy specimens of cases originally classified as PCAC, were reevaluated for cervical and endometrial precursor lesions and LUS involvement. Cases with LUS involvement (LUS+) in the absence of cervical precursor lesions (CPL-) were subjected to PCR analysis for HPV-DNA. LUS+/CPL-/HPV- cases were reclassified as LUS carcinoma (LUSC). All cases were analyzed immunohistochemically for expression of the MMRP proteins MLH1, MSH2, MSH6, PMS2 as well as for expression of ER, vimentin, CEA, and p16 expression. Immunohistochemical expression patterns of PCAC were compared to LUSC using Fisher's exact test.
Results: A total of five cases with a LUS+/CPL-/HPV- status were reclassified as LUSC (5/42, 11.9%). Of the remaining 37 PCAC, 25 (67%) had an IHC-pattern typical for cervical adenocarcinomas (ER-, Vimentin-, CEA+) and 35 (94%) stained moderately to strongly positive for p16. None of the LUSC cases had an IHC pattern typical for cervical adenocarcinomas and none was diffusely positive for p16. All PCAC had retained MMRP expression, but loss of MMRP expression was found in 4/5 LUSC (p< 0.005). One mixed type serous/ endometrioid and one undifferentiated LUSC had loss of MSH2 and MSH6 (suggestive for MSH2 germline mutation). One mucinous LUSC showed isolated loss of PMS2 (suggestive for PMS2 germline mutation), one mixed type serous/ endometrioid LUSC showed loss of PMS2 and MLH1. One LUSC of endometrioid subtype had retained MMRP expression.
Conclusions: Impaired MMRP expression, predictive for Lynch syndrome, is frequent in LUSC and uncommon in genuine PCAC, therefore LUSC should be screened for MMRP expression. As LUSCs with involvement of the uterine cervix are liable to be misclassified as PCAC, uterine carcinoma ambiguous for site of origin need to be subjected to ancillary studies including MMRP expression.
Category: Gynecologic & Obstetrics
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 136, Wednesday Morning