Immunohistochemical study of C-kit [CD117] expression in renal cell carcinoma

ABSTRACT

Renal cell carcinomas [RCCs] represent a heterogeneous group of tumors with potential prognostic and therapeutic differences. Certain subtypes of RCCs are diagnostically challenging owing to their overlapping histopathological features. Ancillary techniques such as immunohistochemistry are essential in these situations. Recently, c-KIT [CDI17] has come into focus as a potential diagnostic marker of some renal tumors, c-KIT also provides a potentially suitable target for targeted tumor therapy. The present study was designed to investigate the immunohistochemical expression of c-KIT [CD117] in renal cell carcinomas [RCCs] in order to evaluate its diagnostic usefulness as a phenotypic marker and to establish the basis for a new possible therapeutic modality. The expression of c-KIT [CD117] was assessed in 49 patients with renal cell carcinomas using immunohistochemistry The diagnostic performance of c-KIT expression was evaluated using Receiver Operating Characteristic [ROC] curve analysis. The present work was conducted on 49 patients with renal cell carcinomas clear cell RCC [CRCC] 30 cases [61.22%]; chromophobe RCC [ChRCC] 9 cases [18.37%]; papillary RCC [PRCC], type 1 5 cases [10.20%]; and carcinoma of the collecting ducts of Bellini [CdRCC] 5 cases [10.20%]. Overall, 11[22.5%] cases showed c-KIT expression 2 [6.7%] CRCC, 7 [77.8%] ChRCC, and 2 [40.0%] CdRCC. Among the study group of RCCs, ChRCC had a statistically significant higher frequency [p=.000] and staining score for c-KIT [p=.000] compared to other subtypes of RCC. In addition, only ChRCC showed membranous pattern of c-KIT staining, while other immunoreactive tumors showed cytoplasmic staining [p=.013]. c-KIT showed a sensitivity of 77.78% and a specificity of 95% for the diagnosis of ChRCC. The positive likelihood ratio was 15.56 and the negative likelihood ratio was 0.23. The positive predictive value was 45% and the negative predictive value was 98.8%. The relation between c-KIT expression [both the frequency and total staining score] and clinicopathological parameters such as age, sex and stage of tumors was not significant. High grade tumors had a statistically significant higher total score of c-KIT expression [p=.023]. c-KIT is frequently and significantly expressed in chromophobe RCC suggesting that it might play a role in its pathogenesis. Immunohistochemical detection of c-MT expression could be used to aid histological diagnosis of chromophobe RCC with a high sensitivity and specificity. The highest diagnostic accuracy of c-KIT expression in ChRCC is reached at a cutoff point of score > 4 accompanied by membranous pattern of staining. The substantial c-Kit immunoreactivity in chromophobe RCC may be of clinical importance especially in the field of targeted therapy