alexa Uncertainty in the Utility of Mismatch Repair Protein Expression measured by Immunohistochemistry in a Multicenter Population-based Study of Epithelial Ovarian Cancer
ISSN: 2161-0681

Journal of Clinical & Experimental Pathology
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Research Article

Uncertainty in the Utility of Mismatch Repair Protein Expression measured by Immunohistochemistry in a Multicenter Population-based Study of Epithelial Ovarian Cancer

Domenico Coppola1,4*, Santo V. Nicosia5, Andrea Doty2, Thomas A Sellers2, Ji-Hyun Lee3, Jimmy Fulp3, Zachary Thompson2,Sanja Galeb2, John McLaughlin6, Steven A Narod7, Joellen Schildkraut6 and Tuya Pal2

1Department of Anatomic Pathology, H. Lee Moffit Cancer Center, Tampa, Florida, USA

2Departments of Cancer Epidemiology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA

3Department of Biostatistics, H. Lee Moffitt Cancer Center, Tampa, Florida, USA

4Department Experimental Therapeutics, H. Lee Moffitt Cancer Center, Tampa, Florida, USA

5Department of Pathology and Cell Biology, University of South Florida, College of Medicine

6Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada

7Centre for Research in Women’s Health, Women’s College Research Institute, Toronto, Canada

*Corresponding Author:
Domenico Coppola, MD
Department of Anatomic Pathology Moffitt Cancer Center
Departments of Oncologic Sciences
University of South Florida 12902 Magnolia Drive Tampa
Florida 33612, USA
E-mail: [email protected]

Received date: June 26, 2012; Accepted date: July 11, 2012; Published date: July 14, 2012

Citation: Coppola D, Nicosia SV, Doty A, Sellers TA, Lee JH, et al. (2012) Uncertainty in the Utility of Mismatch Repair Protein Expression measured by Immunohistochemistry in a Multicenter Population-based Study of Epithelial Ovarian Cancer. J Clin Exp Pathol 2:115. doi:10.4172/2161-0681.1000115

Copyright: © 2012 Coppola D, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

 

Abstract

immunohistochemistry (IHC) for MMR protein expression. Although the utility of IHC has been demonstrated in
colorectal cancer, its utility in ovarian cancer remains incompletely defined. We sought to evaluate the loss of protein
expression of the MMR proteins (MLH1, MSH2 and MSH6) in three population-based samples of epithelial ovarian
cancers.
Methods: IHC staining was performed on full section slides or tissue microarray (TMA) slides for MLH1, MSH2,
and MSH6 protein expression in paraffin-embedded tumor samples. Samples were considered to have loss of
expression (LoE) if one or more proteins had an expression score of < 3 (on a scale of 9). Collection of demographic,
clinical and family history information was attempted in all women.
Results: Of 487 participants in whom IHC was completed, 147 were performed through full section slides and
340 were performed through TMA slides. In the overall sample, LoE of one or more of the MMR proteins was observed
in 12.7%. Notably, the proportion of tumors with LoE was significantly higher in TMAs (17.9%) compared to full section
slides (0.7%) (p <0.001). Finally, tumors with loss of MMR protein expression were more likely to be from individuals
with tumors of non-serous histology (p=0.004).
Conclusions: A substantial proportion of epithelial ovarian cancers have a loss of MMR protein expression.
Protein expression results vary significantly by the tissue sampling methodology utilized, raising concerns about the
clinical utility of this test for ovarian tumors.

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