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Introduction: Renal Cell Carcinoma (RCC), which accounts for 2%-3% of all adult malignant neoplasms with a male-to-female predominance of 1.9 to 1 with typical presentation between 55 and 75 years. The phosphoinositide-3-kinase-protein kinase B/Akt (PI3KPKB/Akt) pathway is a main pathway in control of cell growth. mTOR pathway plays a key role in the pathogenesis of RCC., Material and Methods: Its a prospective observational study. Tissue samples were collected and processed and DNA isolation and sequencing was done to see for any association and expression., Results and Analysis: Polymorphism analysis of the sequence of three genes MTOR, AKT1, and PIK3CA done and found an intronic variant of the MTOR gene (rs3737611) and AKT1 gene (rs2498797) to be significantly associated with clear cell Renal Cell Carcinoma tumor samples., Discussion: This study will help to understand the pathogenesis better and the information can be used to develop new drugs and personalized treatment strategies that are tailored to an individual's genetic makeup. The study identify individuals who are at heightened risk for developing renal cancer and could benefit from targeted screening or preventative measures. Some sample size and definite geographical sample pool remains the main limitation of the study which may not be externally validate the study results., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Eosinophilic solid and cystic renal cell carcinoma (ESCRCC) is an under-recognized, emerging new entity of sporadic renal neoplasms, with an approximate incidence of 0.2% of renal tumors. A total of 60 cases have been reported in the literature till date. ESCRCC are usually seen in adult females, with a low stage and indolent behavior, and rare incidence of recurrence or metastasis. They are solid and cystic tumors with variably sized cysts resembling eosinophilic RCC, showing a characteristic positive immune-expression for PAX-8, CK20 (in ~80% cases) and/or Melan-A (in ~6.7%), with negative CK7 and CA-IX expression. They consistently harbor TSC1 or TSC2 mutations in all tumors, which is a proposed molecular marker for this entity. We here present the first reported case of this rare tumor from India. The tumor was positive for PAX-8, and showed diffuse strong positivity for Melan-A, while was negative for CK7 and CK20. It was an early-stage tumor (T1), managed with partial nephrectomy, with no evidence of any recurrence/metastasis after 1 year of follow-up.

Aim: To assess the VHL gene expression as a prognostic marker in Renal Cell Carcinoma (RCC) and compare it with clinicopathologic features., Materials and Methods: This retrospective observational study was conducted in the department of Urology and Renal Transplantation in Sri Ramachandra Institute of Higher Education and Research, Chennai from August 2016 to August 2018. Thirty patients who have undergone a radical/partial nephrectomy with biopsy proven histological diagnosis of RCC during the study period were included in the study. Data was analyzed using Statistical package for Social Sciences version 17., Results: A complete loss and retained VHL expression were noted in 60% and 40% of the RCC specimens. Association between smoking and VHL expression was found to be statistically significant. There was no statistical significance found between age group, sex, chief complaints, BMI. ECOG score, hypertension, family history, location of tumor, calcification, venous system or lymphnode involvement. However, rT staging, nature of lesion and cut surface, HPE type, pT staging, HPE grade, necrosis and lympho-vascular invasion were also found to be statistically significant., Conclusion: Complete loss of VHL expression was noted in majority of the specimens that leads to the development of RCC. Smoking has been found to be statistically significant in tumors that retain VHL expression which may contributes to more aggressive form of tumor. Association between rT staging, nature of lesion and cut surface, HPE type, pT staging, HPE grade, necrosis and lympho-vascular invasion were also found to be statistically significant., Competing Interests: None

Aim: Heterotrimeric G protein α-subunit Gαs is required for activation of adenylyl cyclase and generation of cyclic adenosine monophosphate (cAMP) in cells and plays a key role in multiple signal transduction pathways, linked to proapoptotic processes in cancer cells. This study investigated whether Gαs gene polymorphism was associated with increased renal cell carcinoma (RCC) risk in the North Indian population. In the present study, genotyping of GNAS1 gene in 196 RCC cases and 250 healthy controls was performed via polymerase chain reaction-restriction fragment length polymorphism., Results: The frequency of homozygous genotype CC was 29.6%, heterozygous TC was 51.5%, and homozygous TT was 18.9% in cases, whereas in controls it was 16.8%, 50.8%, and 32.4%, respectively; thus, there was a significant difference between the two groups (p=0.0001) in the univariate model. Further, multivariate analysis also demonstrated significant association of CC genotype with RCC risk (p=0.002). The high-risk genotype CC of GNAS1 gene showed threefold increase in risk to RCC relative to the TT genotype (unadjusted odds ratio [OR]=3.023, 95% confidence interval [CI]: 1.734-5.270). Whereas multivariate analysis showed a twofold increase in RCC risk among the CC genotype compared with the TT genotype (adjusted OR=2.181, 95% CI: 1.344-3.538). The C allele frequency was found to be significantly higher in RCC patients (55.3%) than in controls (42.2%) as compared with the T allele frequency that was 44.64% in RCC cases and 57.8% in controls. Moreover, patients with the CC genotype showed the worst prognosis in terms of the highest frequency of individuals having higher stages of RCC, but did not show any association with histological grade., Conclusion: Our results suggest that a T393C SNP could be considered as a genetic marker implicated in the pathogenesis of RCC.

In this study, we investigated the association of GSTP1, GSTM1, and GSTP1 genetic variants with renal cell carcinoma (RCC) among North Indian patients. The difference in frequency of the GSTT1 null genotype between cases and control subjects was statistically significant (active ver. null, odds ratio [OR]=0.368; confidence intervals [CI] 95%=0.243-0.557, p=0.001). The differences in the frequency of GSTP1 genotypes were statistically significant (AA ver. AG/GG, OR=1.879; CI 95%=0.355-0.797, p=0.002). Higher allelic frequency of the GSTP1 G allele was associated with RCC cases (G ver. A allele, OR=1.534; 95% CI=1.159-2.030, p=0.003). The gene-gene interaction in terms of three-way combination of GSTM1 null, GSTT1 null, and GSTP1 (AG/GG) resulted in 4.5-fold increase in RCC risk (OR=4.452; 95% CI=2.220-9.294). Similarly, our study revealed that GST polymorphism might be a vital determinant of advancement to higher pathological stages and histological grades of RCC. Our findings suggest that genetic variability in members of the GST gene family may be associated with an increased susceptibility to RCC and its progression.

Aberrant promoter hypermethylation of cancer associated genes occur frequently during carcinogenesis and may serve as a cancer biomarker. The aim of this study was to investigate the occurrence and relevance of promoter methylation of the tumor suppressor DAPK-1, APAF-1 () and SPARC in relation to different pathological stages and histological grades of tumor progression that might act as possible independent prognostic factor in the susceptibility towards renal cell carcinoma (RCC) in North Indian population. Three tumor suppressor gene promoters namely APAF-1, DAPK-1 and SPARC were assessed by methylation-specific PCR (MS-PCR) in 196 primarily resected renal cell tumors paired with the corresponding normal tissue samples. After genomic DNA isolation and sodium bisulfite modification, methylation levels were determined and correlated with standard clinicopathological parameters, pathological stage and Fuhrman nuclear grade of RCC. Significant differences in methylation frequency among the four subtypes of renal tumors were found for APAF-1 (p < 0.001), DAPK-1 (p < 0.001) and SPARC (p = 0.182), when compared with the corresponding normal tissue. Male subjects showed stronger association of methylation frequency of all the three genes with RCC than the female subjects. Additionally, higher frequency of APAF-1, DAPK-1 and SPARC promoter methylation were directly correlated with higher tumor stage (p (trend) < 0.001). Higher frequency of promoter methylation of APAF-1 and SPARC were also associated with higher nuclear grade (p < 0.001 and p = 0.036, respectively). This gene panel might contribute to a more optimal diagnostic coverage and information, improving preoperative assessment and therapeutic decision-making in patients harboring suspicious renal masses.

The renal cell carcinoma (RCC) is a rare condition, accounting for only 3% of all adult malignancies although constituting 90% of kidney cancers. The tumor is immunogenic and the host immune system may modulate the clinical course of the disease. It has been reported that genetic polymorphisms in the interleukin-4-receptor alpha gene are associated with risk and prognosis in RCCs. The present study is aimed at analyzing the presence and significance of the interleukin-4-receptor alpha Ile50Val and Gln576Arg polymorphisms in a group of RCC patients from South India. PCR-RFLP analysis was performed on genomic DNA isolated from blood samples and the genotypes deduced. A significant association was found between the IL4 R alpha Val/Val genotype and increased risk of RCC (OR: 3.45, CI: 1.15-10.38, P: 0.04). The Val/Val genotype was also found to be significantly associated with increased risk in individuals below 54 years (OR: 5.79, CI: 1.33-25.07 P: 0.03) of age and in females (OR: 7.47, CI: 1.4-39.84, P: 0.03). However, no significant association was observed with the Gln576Arg polymorphism. Stratified analysis based on the genotypes and the stage of tumor revealed no significant association. Thus, the present study indicates that IL4Ralpha could be a candidate gene for assessing the risk of RCC.