Diagnostic utility of vimentin, CD117, cytokeratin-7 and caveolin-1 in differentiation between clear cell renal cell carcinoma, chromophobe renal cell carcinoma and oncocytoma

Abstract

Overlapping morphological characteristics pose some difficulties in making a proper diagnosis of clear cell renal cell carcinoma (CCRCC), chromophobe renal cell carcinoma (ChRCC), and oncocytoma, on the basis of hematoxylin–eosin-stained tissue sections. Our objective was to find out a fast, reliable panel of immunohistochemical markers for differentiation between them. The study was carried out on 55 selected renal tumor specimens: 36 cases of CCRCC, seven cases of ChRCC, and 12 cases of oncocytoma. The specimens were stained immunohistochemically for vimentin, CD117, cytokeratin (CK)7, and caveolin (Cav)-1. Sensitivity and specificity for each marker were calculated. Vimentin expression was exclusively observed in CCRCC (100%) and negative in ChRCC and oncocytoma. CD117 was absent in CCRCC, but it was strongly expressed in ChRCC (85.5%) and oncocytoma (91.7%), with high sensitivity and specificity. Most CCRCCs and oncocytomas were negative for CK7 (91.7% and 83.3%, respectively), in contrast to ChRCCs, which showed positivity in nearly 86% of the cases. Good sensitivity and specificity were calculated for CK7 in differentiating studied oncocytic tumors. Cav-1 was positive in ~78% of the CCRCCs and in all ChRCCs, whereas the vast majority of oncocytomas were negative. So the immunoprofile of CCRCC was vimentin+/CD117−/CK7−/Cav-1±, ChRCC was vimentin−/CD117+/CK7+/Cav-1+, and oncocytoma was vimentin−/CD117+/CK7±/Cav-1−. So, by using combination of four markers (vimentin, CD117, CK7, and Cav-1), we achieved excellent sensitivity and specificity for differential diagnosis of CCRCC, ChRCC and oncocytoma.

Combined Immunohistochemistry for the “Three 7” Markers (CK7, CD117, and Claudin-7) Is Useful in the Diagnosis of Chromophobe Renal Cell Carcinoma and for the Exclusion of Mimics: Diagnostic Experience from a Single Institution

“…According to our experience, CK7 may also be positive in the clear cells of CCRCCs with a superimposed tall/columnar or eosinophilic appearance, but these areas are frequently very limited (usually <10%). CD117 labels both the majority of CHRCCs and ROs, commonly with strong and diffuse staining patterns [25]. The SP of CK7 in CHRCC should be higher than that in RO, which is not consistent with the results in our study (CK7 vs. CD117, 0.87 vs. 0.88) because the proportion of RO cases was significantly less than that of other CK7-negative renal cell carcinomas (particularly, CCRCC).…”

Comparative Analysis on Molecular Characteristics of Chromophobe Renal Cancer and Oncocytoma

“…Similarly, S100A1 has sensitivities and specificities at 80-100% and 70-92%, respectively [11,46]. In our study, the sensitivity and specificity for CK7 are 94% and 89% and for S100A1 are 98% and 74% which are similar to previous studies [42][43][44][46][47][48] at transcript level. In comparison, our unsupervised ensemble models have a sensitivity and specificity of 92.4% and 100% for chRCC.…”

“…IHC and special stain markers for distinguishing chRCC and oncocytoma include CK7, S100A1, CD117 (CKIT), kidney specific cadherins, KAI, cyclin D1, and Hale's colloidal iron are currently used to differentiate the tumors in discrepant cases. CK7 has a wide range of sensitivity and specificity, ranging from 73-100% and 71-100%, respectively [41][42][43][44][45] in different studies. Similarly, S100A1 has sensitivities and specificities at 80-100% and 70-92%, respectively [11,46].…”

Metastatic renal cell carcinoma initially presenting as a unilateral breast lump

“…The gold standard of diagnosis is histopathology and supplementary immunohistochemistry. Intracellular proteins such as vimentin [12] and PAX-8 [13] have excellent diagnostic sensitivity for the detection of RCC, both of which were positive in the biopsy of our patient and raised the initial suspicion of an extramammary metastatic source.…”