Department of Obstetrics and Gynecology, School of Medicine, Sapporo Medical University, Sapporo, Japan.
Department of Pathology, School of Medicine, Sapporo Medical University, Sapporo, Japan.
Med Mol Morphol. 2021 Mar;54(1):14-22. doi: 10.1007/s00795-020-00254-6. Epub 2020 May 14.
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.
错配修复蛋白缺陷(dMMR)是结直肠癌的一个有利预后因素。它还与 HLA Ⅰ类分子的异常表达有关,而 HLA Ⅰ类分子是细胞毒性 T 淋巴细胞介导的癌症免疫治疗所必需的。由于 dMMR 也经常在子宫内膜癌(EC)中发现,我们回顾性地研究了 127 例 EC 患者中错配修复蛋白和 HLA Ⅰ类分子的表达情况。在这项研究中,我们从 2005 年到 2009 年招募了在我院接受治疗的 EC 患者,并观察到 2017 年 12 月。通过免疫组织化学检测 MSH6 和 PMS2(错配修复蛋白)和 HLA Ⅰ类分子来评估病变标本。这些分子的表达与临床和病理因素及预后有统计学关系。在 33 例患者中检测到 dMMR,但与 HLA Ⅰ类分子的表达水平无关(P=0.60)。另一方面,出乎意料的是,多变量分析显示 HLA Ⅰ类分子的完整表达与 p53 过表达有关(P=0.004)。dMMR 和 HLA Ⅰ类分子表达降低均不是预后因素。这些结果与结直肠癌的先前发现不一致。EC 和结直肠癌之间结果的差异可能与局部组织免疫微环境的不同有关。