Discovery of disease-causing mutations in BHD, a novel kidney cancer gene associated with renal oncocytoma or chromophobe renal cancer, will contribute to understanding the role of folliculin in pathways common to skin, lung, and kidney development.
Despite the chromosomal numerical abnormalities typical of RO, we classified these tumors as part of the spectrum of PRCC because of their predominant papillary/tubulopapillary architecture, immunoprofile that included reactivity for AMACR, vimentin and lack of reactivity for CD117, all of which is incompatible with the diagnosis of RO.
The remaining 2 carcinomas previously reported as malignant RO owing to cytological atypia and lymph node metastasis showed immunoprofile of RCC(-)/CD117(+) and absence of numeric changes for chromosomes 7, 17, and Y or loss of loci 3p25 or 3p14.
Our results demonstrate that KIT could be a useful immunophenotypic marker for chromophobe RCC and renal oncocytoma; therefore, it has value for the precise classification of renal cortical epithelial tumors.
In this study we have investigated immunohistochemical biomarkers (cytokeratin 7/CK7, Caveolin-1/Cav-1 and S100 calcium-binding protein A1/S100A1) to aid in this difficult differentiation and attempted to validate their use in human renal tumour tissue to assess their discriminatory ability, particularly for chRCC and RO, in an Australian cohort of patients.
S100A1 was moderately-to-strongly positive in 45 of 56 (80%) RO and in 1 of 13 (8%) ChRCC (P < .001), with 39 of 56 (70%) and 2 of 13 (15%) cases, respectively showing positivity in >50% of tumor cells (P< .001).
All 10 cases were analyzable by FISH and showed chromosomal abnormalities similar to that usually seen in RO (i.e. loss of 1p36 gene loci, loss of chromosome Y, rearrangement of CCND1 and numerical changes of chromosome 14).
The data also show that cyclin D1 overexpression and CCND1 rearrangements by fluorescence in situ hybridization are absent in chromophobe renal cell carcinoma, suggesting that these are useful when differentiating between renal oncocytoma and chromophobe renal cell carcinoma.
The α-IC cell marker SLC4A1 was seen in 60% of RO and 11% of chRCC, whereas staining for the β-IC cell marker SLC26A4 was negative in all but one tumor.
Although the origin of RO remains unclear, our findings suggest that FOXI1 immunohistochemistry is useful in differential diagnosis of RO from chRCC with overlapping histology.
The differences in staining with cyclin D1, p16, survivin, CD138 and Ki-67 turned out to be statistically insignificant in differentiating ChRCC from RO.
The α-IC cell marker SLC4A1 was seen in 60% of RO and 11% of chRCC, whereas staining for the β-IC cell marker SLC26A4was negative in all but one tumor.
Despite the chromosomal numerical abnormalities typical of RO, we classified these tumors as part of the spectrum of PRCC because of their predominant papillary/tubulopapillary architecture, immunoprofile that included reactivity for AMACR, vimentin and lack of reactivity for CD117, all of which is incompatible with the diagnosis of RO.
Fluorescence in situ hybridization was performed on 65 cases (ChRCC, n = 33; RO, n = 32) to verify hemizygous deletion of RB1 (17/33, 52%) or ERBB4 (11/33, 33%) in ChRCC, but not in RO (0/32, 0%).