Department of Urology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
Jpn J Clin Oncol. 2021 Apr 1;51(4):639-645. doi: 10.1093/jjco/hyaa207.
The prevalence and molecular characteristics of deficient mismatch repair prostate cancer in the Japanese population have scarcely been investigated.
Immunohistochemistry for mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) was performed in formalin-fixed paraffin-embedded sections prepared from resected primary prostate cancers in patients who underwent prostatectomy at our institution between January 2001 and May 2016. Genetic and/or epigenetic alterations of mismatch repair genes were investigated in patients with any loss of mismatch repair protein expression in the tumour.
Of the 337 patients, four (1.2%) showed loss of mismatch repair protein expression on immunohistochemistry. All four patients showed loss of both MSH2 and MSH6 protein expression. Genetic testing was performed in two of the four patients, demonstrating no pathogenic germline alterations were present. In each of these two patients, at least one somatic alteration inactivating MSH2 without MSH2 hypermethylation was identified, leading to the diagnosis of supposed 'Lynch-like syndrome'. Patients with deficient mismatch repair prostate cancer were at a significantly higher stage (pT2pN0 vs. pT3-4pN0/pTanypN1, P = 0.02) and had a greater Gleason score (<8 vs. ≥8, P < 0.01) than those with proficient mismatch repair prostate cancer.
The prevalence of deficient mismatch repair prostate cancer in the Japanese hospital-based prostatectomized population was extremely low. To improve screening efficacy for deficient mismatch repair prostate cancer, screening candidates can be limited to patients with locally advanced, node-positive and/or Gleason score of 8 or greater prostate cancer. Universal tumour screening for Lynch syndrome seems ineffective in patients with prostate cancer.
在日本人群中，缺陷性错配修复前列腺癌的流行情况及其分子特征尚未得到充分研究。
对本机构 2001 年 1 月至 2016 年 5 月期间接受前列腺切除术的患者的原发性前列腺癌切除标本进行福尔马林固定、石蜡包埋切片的免疫组织化学分析，以检测错配修复蛋白（MLH1、MSH2、MSH6 和 PMS2）。对肿瘤中任何错配修复蛋白表达缺失的患者进行错配修复基因的遗传和/或表观遗传改变检测。
在 337 例患者中，有 4 例（1.2%）免疫组织化学检查显示错配修复蛋白表达缺失。这 4 例患者均表现为 MSH2 和 MSH6 蛋白表达缺失。对其中的 2 例患者进行了基因检测，结果未发现致病性种系改变。在这 2 例患者中，均发现至少一个失活 MSH2 的体细胞改变，且无 MSH2 高甲基化，从而诊断为疑似“林奇样综合征”。与错配修复功能正常的前列腺癌患者相比，错配修复功能缺陷的前列腺癌患者的肿瘤分期更高（pT2pN0 与 pT3-4pN0/pTanypN1，P=0.02），Gleason 评分更高（<8 与≥8，P<0.01）。
日本医院前列腺癌患者中，错配修复功能缺陷型前列腺癌的发生率极低。为提高错配修复功能缺陷型前列腺癌的筛查效果，可以将筛查对象仅限于局部晚期、淋巴结阳性和/或 Gleason 评分≥8 的前列腺癌患者。对前列腺癌患者进行林奇综合征的普遍肿瘤筛查似乎效果不佳。
