Androgen receptor pathway in clear cell renal cell carcinoma

Renal cell carcinoma represents the third most frequent urological neoplasm and about 70% of kidney cancers are clear cell renal cell carcinoma (CCRCC), with an incidence ratio of about 2:1 between males and females. Approximately 20% of patients present with metastatic disease at onset and 30% of patients who undergo radical surgery for localized disease recur. Currently, in addition to the surgical approach, various oncological strategies are used in the treatment of CCRCC, but most patients acquire resistance to these therapies. The detailed mechanisms leading to drug resistance are unclear and their identification is crucial for the development of new therapies. Recent studies hypothesize that RCC may be influenced by exposure to androgen hormones, that promote development and progression of RCC. The aim of this study is to evaluate the immunohistochemical expression of the androgen receptor (AR) and its interactors in a cohort of patients affected by CCRCC and to investigate their association with clinicopathological features. In this study, 40 cases were examined with immunohistochemistry for the expression of AR, pVHL, 14-3-3 and PPP5C. We observed a highly significant inverse association between AR expression and tumour grade, and in particular a significant inverse correlation between AR expression and the presence of sarcomatoid and/or rhabdoid components. pVHL, pan 14-3-3 and PPP5C expression was also closely associated with tumour grade, but with a different expression pattern in terms of subcellular localization compared to AR. Additionally, AR, pVHL, pan 14-3-3 and PPP5C expression was associated with the presence of local and/or distant recurrences. These findings suggest that AR may play distinct roles during RCC development and further studies are needed to elucidate the complex biological mechanisms underlying different phases of tumour progression.