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TRPM8 蛋白在激素初治的局部和淋巴结转移性前列腺癌中的表达。

TRPM8 protein expression in hormone naïve local and lymph node metastatic prostate cancer.

机构信息

Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Italy.

Pathology Unit, Department of Clinical Services, Santa Chiara Hospital, Trento, Italy.

出版信息

Pathologica. 2021 Apr;113(2):95-101. doi: 10.32074/1591-951X-262. Epub 2021 Mar 18.

Abstract

OBJECTIVE

Prostate cancer (PCa) is the second most common malignancy in men. Radiotherapy and surgery successfully control organ-confined tumors, although, locally advanced/high-risk PCa frequently progress to the metastatic stage of the disease, which is uncurable. Identification of novel strategies to improve the efficacy of standard clinical protocols is a primary need. Among the molecular targets of potential clinical interest recently highlighted by accurate preclinical studies, the TRPM8 cation channel is particularly promising. In this study, we aim at establishing a standardized immunohistochemistry protocol to evaluate TRPM8 expression in normal and pathological prostate tissues.

METHODS

The specificity and sensitivity of TRPM8 antibody ACC-049 was validated in different human prostate cell lines by western blot and immunocytochemistry analyses. Expression of the TRPM8 channel in normal and pathological prostate tissue was evaluated by immunohistochemistry using a tissue microarray containing 58 cases of prostate adenocarcinomas and in primary and lymph nodes metastatic human PCa matched specimens.

RESULTS

TRPM8 expression marks luminal epithelial cells in benign prostate tissue. In malignant lesions of the prostate, TRPM8 expression is frequently more abundant in advanced stages of the disease (PCa stage III/IV). Finally, lymph node metastases and matched primary tumors show similar amounts of the channel.

CONCLUSIONS

Collectively, our results reinforce the importance of TRPM8 as prostate biomarker and emphasize the value of the channel as promising novel molecular target for the treatment of prostate adenocarcinoma.

摘要

目的

前列腺癌(PCa)是男性中第二常见的恶性肿瘤。放疗和手术可成功控制器官局限性肿瘤,但局部晚期/高危 PCa 常进展为疾病的转移性阶段,这是无法治愈的。寻找提高标准临床方案疗效的新策略是首要需求。在最近通过精确的临床前研究突出显示的具有潜在临床意义的分子靶标中,TRPM8 阳离子通道尤其有前景。在这项研究中,我们旨在建立标准化免疫组织化学方案,以评估正常和病理性前列腺组织中 TRPM8 的表达。

方法

通过 Western blot 和免疫细胞化学分析,在不同的人前列腺细胞系中验证了 TRPM8 抗体 ACC-049 的特异性和敏感性。使用包含 58 例前列腺腺癌和原发性及淋巴结转移性人 PCa 匹配标本的组织微阵列,通过免疫组织化学评估 TRPM8 通道在正常和病理性前列腺组织中的表达。

结果

TRPM8 表达标记良性前列腺组织中的腔上皮细胞。在前列腺的恶性病变中,TRPM8 表达在疾病的晚期(PCa 分期 III/IV)更为丰富。最后,淋巴结转移和匹配的原发性肿瘤显示出相似数量的通道。

结论

总的来说,我们的结果强调了 TRPM8 作为前列腺生物标志物的重要性,并强调了该通道作为治疗前列腺腺癌有前途的新分子靶标的价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44ed/8167398/4a12788f85e2/pathol-2021-02-95-g001.jpg

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