Panic Andrej, Reis Henning, Wittka Alina, Darr Christopher, Hadaschik Boris, Jendrossek Verena, Klein Diana
Department of Urology, West German Cancer Center, University of Duisburg-Essen, University Hospital Essen, Essen, Germany.
Institute of Pathology, West German Cancer Center, University of Duisburg-Essen, University Hospital Essen, Essen, Germany.
Front Oncol. 2021 Mar 31;11:606122. doi: 10.3389/fonc.2021.606122. eCollection 2021.
Various types of human cancers were characterized by an altered expression of epithelial or stromal caveolin-1 (CAV1). However, the clinical significance of CAV1 expression in penile cancer remains largely unknown. Here the expression patterns of CAV1 were analyzed in a retrospective cohort (n=43) of penile squamous cell carcinomas (SCC). Upon penile cancer progression, significantly increased CAV1-levels were determined within the malignant epithelium, whereas within the tumor stroma, namely the fibroblastic tumor compartment harboring activated and/or cancer associated fibroblasts, CAV1 levels significantly decline. Concerning the clinicopathological significance of CAV1 expression in penile cancer as well as respective epithelial-stromal CAV1 distributions, high expression within the tumor cells as well as low expression of CAV1 within the stromal compartment were correlated with decreased overall survival of penile cancer patients. Herein, CAV1 expressions and distributions at advanced penile cancer stages were independent of the immunohistochemically proven tumor protein p53 status. In contrast, less differentiated p16-positive tumor epithelia (indicative for human papilloma virus infection) were characterized by significantly decreased CAV1 levels. Conclusively, we provide further and new evidence that the characteristic shift in stromal-epithelial CAV1 being functionally relevant to tumor progression even occurs in penile SCC.
多种类型的人类癌症的特征是上皮或基质小窝蛋白-1(CAV1)表达改变。然而,CAV1在阴茎癌中的临床意义仍 largely unknown。在此,对一组回顾性阴茎鳞状细胞癌(SCC)队列(n = 43)中CAV1的表达模式进行了分析。在阴茎癌进展过程中,在恶性上皮内测定到CAV1水平显著升高,而在肿瘤基质中,即含有活化和/或癌症相关成纤维细胞的成纤维细胞肿瘤区室中,CAV1水平显著下降。关于CAV1在阴茎癌中的表达的临床病理意义以及各自的上皮-基质CAV1分布,肿瘤细胞内的高表达以及基质区室中CAV1的低表达与阴茎癌患者总体生存率降低相关。在此,晚期阴茎癌阶段的CAV1表达和分布与免疫组化证实的肿瘤蛋白p53状态无关。相反,分化程度较低的p16阳性肿瘤上皮(指示人乳头瘤病毒感染)的特征是CAV1水平显著降低。总之,我们提供了进一步的新证据,即基质-上皮CAV1的特征性转变与肿瘤进展在功能上相关,甚至在阴茎SCC中也会发生。