Elsevier

Urology

Volume 83, Issue 2, February 2014, Pages 510.e19-510.e24
Urology

Basic and Translational Science
The Expression and Evaluation of Androgen Receptor in Human Renal Cell Carcinoma

https://doi.org/10.1016/j.urology.2013.10.022Get rights and content

Objective

To investigate the expression of androgen receptor (AR) with clinical and pathologic features in patients with renal cell carcinoma (RCC) and to explore the function of AR using human RCC cells.

Materials and Methods

The expression of AR was detected by immunohistochemistry in 44 adjacent normal kidney tissues of 120 RCC patients and also in 16 metastatic RCC patients with their respective primary and metastatic tissue samples. The expression of AR was examined by western blot in commonly used human RCC cell lines and normal kidney epithelial cells, and the luciferase assay was performed in those AR-positive RCC cells.

Results

The expression rate of AR was higher in adjacent normal kidney (90.9%) than in RCC tissues (30.0%, P <.001), and it was negatively associated with pT stage and Fuhrman's grade. Specifically, there were 40.7% AR-positive cases in pT1 compared with 8.0% in pT3 (P = .013), and 50.0% of grade I cases were found to be AR positive compared with 12.9% in grade III (P = .008). AR expression was slightly higher in primary RCC tissues (12.5%) than their respective metastases (0%, P = .484). AR strongly expressed in CAKI-2 and OSRC-2 cells with little transactivation, which might indicate that AR in those 2 RCC cells has little function.

Conclusion

Our results suggest that any attempt to investigate the roles of AR in RCC progression might need to combine the detection of AR expression in tissue samples with examining its function to make a correct correlation between AR and RCC progression.

Section snippets

Tissue Samples

One hundred twenty paraffin embedded RCC specimens from 73 male and 47 female patients, 44 adjacent normal kidney tissue specimens from 24 male and 20 female patients, and 16 primary RCC tissue specimens with their respective metastatic tissue specimens from 12 male and 4 female patients who received radical or partial nephrectomy and cytoreductive nephron-sparing surgery, respectively, between January 2000 and March 2012 were retrieved from the files of the Department of Urology, the First

AR Expression Rate Is Higher in Adjacent Normal Kidney Tissues Than in RCC Tissues

The IHC staining demonstrated that the adjacent normal kidney tissue specimens (40 of 44, 90.9%) had higher AR expression rate than RCC tissue specimens (36 of 120, 30.0%, P <.001; Table 1, Supplementary Fig. 1). In addition, the positive AR staining could mainly be found in the cytoplasm of renal tubular epithelial cells; however, RCC tissue samples showed majority nuclear AR staining (arrows in Supplementary Fig. 1). There was no significant difference in AR-positive rate between male (24 of

Comment

The disappointing results of radiotherapy, chemotherapy, and immunotherapy in metastatic RCC and the gender difference in tumor incidence have raised the interest to explore the role of hormone receptors in clinical RCC tissue samples and investigate the potential of antihormone therapy to battle RCC. However, results from previous studies remained controversial, and RCC tumor samples used in these studies were also limited.8, 9, 10, 11, 12 Loda et al8 analyzed AR expression with negative

Conclusion

Our clinical and cell line data demonstrated that the expression of AR might negatively correlate with the progression of RCC by IHC staining using clinical RCC tissue samples, but transactivation assays found AR expression might not directly link to AR function in RCC cell lines. This finding might raise the conclusion of any attempt of using the status of AR expression to link with RCC progression might need to combine the detection of AR expression in clinical tissue samples with examining

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      Chen et al. found AR suppressed miR-145 to promote ccRCC progression [33]. These results stand in contrast to the other reports using immunohistochemistry analysis indicating that AR expression was less frequent in metastatic RCC than primary RCC tissues [34–37]. Zhao et al. found a higher expression of AR was associated with improved overall survival in ccRCC [38].

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    Guodong Zhu, Liang Liang, and Lei Li contributed equally.

    Financial Disclosure: The authors declare that they have no relevant financial interests.

    Funding Support: This study was supported in part by the grant from National Natural Science Foundation of China (NSFC: 30901501 to Guodong Zhu), the National High Technology Research and Development Program of China (863 Program, No. SS2014AA020607 to Lei Li), US National Cancer Institute grants (CA122840 and CA127300), and George H. Whipple Professorship Endowment and National Science Council and Taiwan Department of Health Clinical Trial and Research Center of Excellence grant DOH99-TD-B-111-004 (China Medical University, Taichung, Taiwan).

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