Nghiem Belinda, Zhang Xiaotun, Lam Hung-Ming, True Lawrence D, Coleman Ilsa, Higano Celestia S, Nelson Peter S, Pritchard Colin C, Morrissey Colm
Department of Urology, University of Washington, Seattle, WA, USA.
State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau (SAR), China.
Asian J Urol. 2016 Oct;3(4):223-228. doi: 10.1016/j.ajur.2016.09.002. Epub 2016 Sep 12.
Although the utility of immunohistochemistry (IHC) for assessing mismatch repair (MMR) protein expression has been demonstrated in solid tumors including primary prostate cancer (PCa), its utility has not been assessed in castration-resistant PCa (CRPC).
Tissue microarrays were constructed from 127 radical prostatectomies and 155 CRPC metastases from 50 patients. MMR (MLH1, MSH2, MSH6, and PMS2) expression was assessed by IHC and gene expression arrays. Associations between MMR protein expression in PCa and CRPC and biochemical recurrence (BCR) or time from diagnosis to death respectively were determined.
There was no correlation between levels of MMR protein and BCR. Absence of MSH2 and MSH6 was the most pronounced at 15% and 22% in PCa and 17.8% and 16% in CRPC patients, respectively. MSH2 and MSH6 protein were absent in 9.4% and 8% of PCa and CRPC respectively. Absence of individual MMR proteins did not correlate with BCR or time from diagnosis to death. However absent MSH2/MSH6 in CRPC was associated with shorter time to death ( = 0.0006). Loss of MSH2 was verified at the gene expression level. This finding correlated with microsatellite instability previously reported in this CRPC cohort.
The absence of MLH1, MSH2, MSH6, and PMS2 protein and combinations thereof are frequent in PCa. Loss of MSH2/MSH6 protein may predict poor outcome in patients with CRPC.
尽管免疫组化（IHC）在包括原发性前列腺癌（PCa）在内的实体瘤中评估错配修复（MMR）蛋白表达的效用已得到证实，但其在去势抵抗性前列腺癌（CRPC）中的效用尚未得到评估。
从50例患者的127例根治性前列腺切除术和155例CRPC转移灶构建组织微阵列。通过免疫组化和基因表达阵列评估MMR（MLH1、MSH2、MSH6和PMS2）表达。分别确定PCa和CRPC中MMR蛋白表达与生化复发（BCR）或从诊断到死亡时间之间的关联。
MMR蛋白水平与BCR之间无相关性。PCa患者中MSH2和MSH6缺失最为明显，分别为15%和22%，CRPC患者中分别为17.8%和16%。PCa和CRPC中分别有9.4%和8%的患者不存在MSH2和MSH6蛋白。单个MMR蛋白的缺失与BCR或从诊断到死亡的时间无关。然而，CRPC中MSH2/MSH6缺失与较短的死亡时间相关（P = 0.0006）。在基因表达水平验证了MSH2的缺失。这一发现与该CRPC队列先前报道的微卫星不稳定性相关。
PCa中MLH1、MSH2、MSH6和PMS2蛋白及其组合的缺失很常见。MSH2/MSH6蛋白的缺失可能预示CRPC患者预后不良。
