Immunohistochemical Distinction of Renal Cell Carcinoma from Other Carcinomas With Clear-Cell Histomorphology

Abstract

Clear-cell renal cell carcinoma (CC-RCC) is the most common primary kidney malignancy, yet this morphology is not unique to renal primary tumors, as clear-cell variants of numerous nonrenal carcinomas of varying lineages exist. Therefore, because of CC-RCC's ability to metastasize to nearly any anatomic location, ancillary studies such as immunohistochemistry are often needed to establish the diagnosis. Despite CD10 and renal cell carcinoma monoclonal antibody (RCCma) being touted as sensitive and specific markers, some have suggested that more recent stains including PAX-2, PAX-8, or adipophilin (ADP) are more robust markers of CC-RCC. In this study, 26 cases of CC-RCC, and 51 nonrenal carcinomas with clear-cell histomorphology (CCM) were stained with CD10, RCCma, PAX-2, PAX-8, and ADP. CA-125 was also included to help distinguish CC-RCC from Müllerian clear-cell carcinomas, due the known expression of PAX-2 and PAX-8 in both these entities. RCCma highlighted 77% of CC-RCC and 27% of the CCM group, whereas CD10 was positive in 85% and 25%, respectively. ADP highlighted all CC-RCC and 45% of CCMs. PAX-2 was positive in 81% of CC-RCC and 24% of CCM, whereas PAX-8 stained 100% of CC-RCC and 39% of CCM. Müllerian-derived tumors (clear-cell carcinomas of the ovary, vagina, and cervix) were positive with PAX-2 and PAX-8 in 69% and 100% of cases, respectively. No cases of CC-RCC stained with CA-125, whereas 88% of the Müllerian-derived tumors were positive. In summary, although new markers such as PAX-2 and PAX-8 tend to be more sensitive markers of CC-RCC, they lose specificity when Müllerian tumors are included. Inclusion of a classic renal marker such as CD10 or RCCma in the immunohistochemical panel, as well as CA-125 obviates this difficulty.

Adipophilin as prognostic biomarker in clear cell renal cell carcinoma

“…Adipophilin is one of the important players in lipid metabolism, responsible for storage of lipid droplets in all types of cells [4, 5]. Some recent studies show that many tumors overexpress adipophilin [6–22], especially those with clear cell histology [10, 11]. Several small reports showed that renal cell carcinoma (RCC) cells also overexpress adipophilin [10, 11, 23–27] and one major study [24] reported the prognostic role of this biomarker in clear cell subtype on transcript level.…”

A Case Report: Metastasis of Clear Cell Ovarian Cancer in Morrison’s Pouch as Differential Diagnosis to Exophytic Kidney Tumor

“…Unfortunately, they are both also positive regarding clear cell from the ovary [10]. This patient was amongst others negative for estrogen, Ca-125, CD10 and PAX8.…”

Biomarkers Role in Prognosis and Survival Outcomes in Patients with Renal Tumors: Review Article

“…PAX-2 was positive to ccRCC by 81% and was positive in 24% of clear cell morphology group. PAX-8 in ccRCCgroup was 100% positive and was 39% positive in the clear cell morphology group [11]. The study concluded that PAX-2 and PAX-8 are sensitive markers to ccRCC and they lose their specificity in the presence of mullerian tumor cells [11].…”

“…However, currently there is no consensus in regard to what biomarker should be used in RCC classification [10]. Various RCC associated biomarkers have been studied including PAX-2/PAX8, CAIX, adipophillin (ADP), CD10, and monoclonal antibody RCC marker (RCCma) [11]. PAX, CAIX and vimentin are biomarkers that might be promising in RCC prognostic significance nowadays.…”