Journal
MEDICAL MOLECULAR MORPHOLOGY
Volume 54, Issue 1, Pages 14-22Publisher
SPRINGER JAPAN KK
DOI: 10.1007/s00795-020-00254-6
Keywords
Mismatch repair proteins deficiency; HLA class I; Endometrial carcinoma; Immunohistochemistry; Adaptive immune escape
Categories
Funding
- Japan Society for the Promotion of Science (JSPS) [17H01540]
- Project for Cancer Research and Therapeutic Evolution (P-CREATE) [19cm0106309h0004]
- Japan Agency for Medical Research and Development (AMED)
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In a study on endometrial cancer patients, it was found that dMMR was not correlated with the expression level of HLA class I molecules, while intact expression of HLA class I molecules was associated with p53 overexpression. Neither dMMR nor decreased expression of HLA class I molecules were prognostic factors in endometrial cancer.
Mismatch repair protein deficiency (dMMR) is a favorable prognostic factor in colorectal cancer. It is also associated with aberrant expression of HLA class I molecules, which are required for cytotoxic T lymphocyte-mediated cancer immunotherapy. Because dMMR is frequently also found in endometrial cancers (ECs), we retrospectively investigated the expression of mismatch repair proteins and HLA class I molecules in 127 EC patients. In this study, EC patients being treated in our hospital were recruited from 2005 to 2009 and observed until December 2017. Lesion specimens were evaluated via immunohistochemistry for MSH6 and PMS2 (mismatch repair proteins) and HLA class I molecules. Expression of these molecules was statistically related to clinical and pathological factors and prognosis. dMMR was detected in 33 patients and did not correlate with the expression level of HLA class I molecules (P = 0.60). On the other hand, unexpectedly, multivariate analysis revealed that intact expression of HLA class I molecules was associated with p53 overexpression (P = 0.004). Neither dMMR nor decreased expression of HLA class I molecules were prognostic factors. These results are inconsistent with previous findings for colorectal cancer. A distinctive local tissue immune microenvironment would underlie the discrepancy in the results between EC and colorectal cancer.
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