[1211] Microsatellite Instability Influences Expression of Endometrial Carcinoma Biomarkers

E Okoye, A Bruegl, B Fellman, R Luthra, R Broaddus. MD Anderson Cancer Center, Houston, TX

Background: Endometrial carcinomas can have a wide range of biomarker expression, even when tumor histotype and grade are constant. The basis for such variability is not known. The purpose of this study was to examine the effect of microsatellite instability (MSI) on the immunohistochemical expression of clinically relevant biomarkers.
Design: 408 consecutive, unselected endometrial carcinomas were evaluated for MSI via immunohistochemical testing of DNA mismatch repair proteins and MLH1 methylation. Loss of immunohistochemical expression of MLH1, MSH2, MSH6, or PMS2 was defined as MSI-high; positive expression was defined as MS-stable. Immunohistochemistry for ER, PR, CK7, CK20 and Pax-8 was evaluated in 80 grade 2 endometrioid carcinomas from this set (40 MSI-high, 40 MS-stable). Cases were matched for histotype, grade, and age. These biomarkers were chosen because they are used in the diagnostic work-up of endometrial biopsies or tumors of unknown primary origin. Percent tumor cells positive for each biomarker was recorded.
Results: Percent tumor cells CK7+ was significantly lower in the MSI-high group (median 45%) compared to the MSS group (median 78%; p=0.008).

Tumors with an immunophenotype of CK7 low and Pax-8 low were more commonly MSI-high (42.5%) compared to MS-stable (20%). The combined immunophenotype CK7 high, ER high and PR high was more common in the MS-stable group (42.5% of all cases) compared to MSI-high (20%).

CK7/ER/PR Immunoprofiles
CK 7 high/ER high/PR high42.5%20%
CK 7 low/ER high/PR high25%37.5%
CK 7 high/ER low/PR low12.5%7.5%
CK 7 low/ER low/PR low0%7.5%

CK20 was minimally expressed in both groups and was thus not affected by MSI.
Conclusions: MSI influences the expression of clinically important biomarkers for endometrial cancer. These results need to be considered when considering carcinomas of unknown primary origin. Given the decreased number of CK7 high/ER high/PR high tumors in the MSI-high group, mismatch repair defects may contribute to the variability of responsiveness of endometriod adenocarcinomas to hormonal manipulation.
Category: Gynecologic & Obstetrics

Tuesday, March 5, 2013 9:30 AM

Poster Session III # 121, Tuesday Morning


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