Introduction

Renal cell carcinoma (RCC) is the foremost different urological malignancy among adults 1. The most prevalent form of malignancy RCC is clear cell RCC (ccRCC) and represents over 90% of malignant kidney tumors 2. The androgen receptor (AR) sequence is found at chromosome Xq11-12 and includes of eight exons 3. Prevalence of the AR is appeared in several parts of the body, principally in sexual parts of men. Also, it was reported in breast, bladder, liver, gastrointestinal 4. High AR expression is potential prognosis factor in bladder cancer 5, and it created longer life in patients with serous carcinoma of the ovary 6, an agent for progressive the squamous cell carcinoma of head and neck 78. We tend to are responsive to only rare studies evaluating AR immunohistochemical staining in RCC 91011. Though the targeted therapy creates an effective route for advanced RCC patients 12, the relationship between AR expression and RCC progression stay uncertain until now 13. This meta-analysis reports the expression of AR and its relation with some pathological factors in RCC.

Methods

Results

After primary searches, 1141 articles identified. Twenty one studies remained after we excluded the non-relevant studies. Then, twelve studies were removed based on reasons (five conference papers, three reviews, two articles without full text, one letter to editor, and one database). At last, nine of them remained for analysis (Figure 1).

From nine studies 91011141516171819, two studies 1417 were Germany, two studies 1519 were USA and others were from Austria 9, Korea 10, China 11, Italy 16 and Japan 18. From 1447 patients 91011141516171819, 345 AR expression exist. One hundred seventy-one cases in four studies 9101118 of meta-analysis study were male, and 59 cases were female (sum=202). Mean age (min-max) in two studies was 60.06 (29-82). Three studies 9111418 on pT stage in 132 patients with expression AR showed 51 cases pT stage 1, 20 cases pT stage 2, 41 cases pT stage 3. And also, 160 low grade versus 42 high-grade cases exist in four studies 9101118 (Table 1).

AR Expression

The prevalence of AR expression in RCC patients has been reported in Figure 2by the ER. The pooled ER of the studies was 28.2% (95% CI=16.3%-44.3%; P=0.009). The Begg’s and Egger’s tests didn’t show publication bias (P=0.53 and P=0.75, respectively) (Figure 3).

AR expression and tumor grade

Among three studies (502 cases), heterogeneity was existed (I= 85.80%, p =0.0) in a fixed‑effects model. Correlation between AR expression and low grade was positive (OR, 1.98; 95% CI, 1.44-2.71; P<0.01) (Figure 4).

AR and pT stage

Among three studies (848 cases), heterogeneity was not existed (I= 4.3%, p = 0.353). Correlation between AR expression and low pT-stage was positive (OR, 4.04; 95% CI, (3.10-5.26); P< 0.01) (Figure 5).

Discussion

Radiotherapy, chemotherapy, and immunotherapy used for treat metastatic RCC patients 12. But, a lot of controversial for treatment of this malignancy are existed until now 1317. Moreover, AR expression has been related to chemo-responsiveness 20. Exaggerated AR expression was related to attenuate responsiveness and exaggerated migration of tumor cells 21. The clear cell RCC resists chemotherapy and radiation with a restricted therapeutic period of the anti-angiogenesis targeted therapy (6–15 months) 22. Clinical researchers have disclosed that some patients reply to endocrine therapy objectively or subjectively 2324. AR can help to the pathobiology of breast malignancy 25, and maybe inhibition of androgen sign had a therapeutic role in it 26. Firstly, AR was observed in cancerous renal tissues and then appears in other urinary organs like prostate and then breast cancer 27. Nakano., who noted that patients with RCC showing immunoreactivity for one or a lot of hormone receptors (ER, PR and/or AR) had a considerably higher survival rate 18. A cohort found that AR expression in clear cell RCC was prognostic which high expression 28. Cut off for express AR reported from 12.9% to 100% 293031. AR expression found in non-invasive urothelial malignancies as compared to invasive urothelial malignance 3233.

Consequently, AR immunoreactivity was related to renowned favorable prognostic factors, like tiny tumor size, low pT stage (more than 30% in pT1a tumors) in addition as low histological grade 34. The AR-positive rate ranged from 16.3%-44.3% in RCC tissues in this study. Noh ., 10 and Concolino ., 16 showed the level of AR-positive is higher than our meta-analysis. In other hands Langne., 9 and Klotzl ., 17 demonstrated that the AR-positive is lower than in this study among RCC patients. Nine studies (1,447 cases) surveyed for AR expression in RCC patients in the meta-analysis and also expressed relationship tumor grades and pT stages with it. Zhu , 11 incontestable that AR expression rate was negatively accompanied pT stage and Fuhrman’s grade in RCC patients. Also, this relationship was indicated by Foersch, 14 and Langner Zhu ., 11 reported prevalence of AR had a negative relationship with pT stage and grade in RCC patients. Foersch ., 14 and Langner .,9 reported the results opposite of him. Noh ., 10 said AR expression related with the histological nuclear grade (p<0.027) and TNM stage (p<0.002). The meta-analysis showed AR expression correlated with low grade and pT stage positively.

Conclusion

As our knowledge, this study is first meta-analysis to research the impact of AR expression on RCC patients. The current study showed the level of expression of AR and its relative with tumor grade and pT stage in RCC patients. Additional studies are needed to the role of AR expression in these patients.

Competing Interests

The author(s) declared no conflicts of interest.

Authors' Contributions

Conceptualization: ES MP

Formal analysis: ES

Methodology: ES HA

Project administration: ES MP HA HM

Software: ES

Validation: HM HA

Writing — original draft: ES

Writing — review & editing: ES MP HA HM

Abbreviations

AR: Androgen Receptor

ccRCC: Clear Cell Renal Cell Carcinoma

CI: Confidence Interval

ER: Estrogen ReceptorpT Stage: Pathologic Tumor StagePR: Progesterone ReceptorRCC: Renal Cell Carcinoma