Abstract
BackgroundRenal cell carcinoma (RCC) with sarcomatoid differentiation is a relatively rare tumor containing both carcinoma and sarcomatoid components. However, there has not been a systemic study on immunophenotypes of renal cell carcinoma with sarcomatoid differentiation, especially using some renal specific immunohistochemical markers. In this study, we aimed to comprehensively investigate the distinct immunophenotypes of RCC with sarcomatoid differentiation to analyze the pathogenesis of sarcomatoid differentiation and identify new prognostic factors in RCC with sarcomatoid differentiation.MethodsA total of 42 cases of RCCs with sarcomatoid differentiation were enrolled into the study. Immunohistochemistry study was performed on tissue microarrays to evaluate the expressions of 19 immunohistochemical markers including a series of epithelial, mesenchymal markers and RCC specific markers. Kaplan-Meier method was applied to assess the prognostic values of CD10, CAIX, p53 and Bcl-2.ResultsHistologically, 42 cases of RCCs with sarcomatoid differentiation presented with different proportions of carcinoma and sarcomatoid components. The cohort contained 35 cases of clear cell renal cell carcinoma (CCRCC) and 7 cases of chromophobe renal cell carcinoma (ChRCC) based on the carcinoma components. Immunohistochemically, all cases were positive for vimentin, and 80% of cases showed immunostaining for at least one epithelial marker, such as CK, EMA, CK7 and CK18. Notably, the expression rates of CAIX, CD10 and PAX8 in sarcomatoid cells were 76%, 76% and 64%, respectively. The carcinoma component of the tumors showed differentient labeling for CAIX, CD10, vimentin, CK7 and CD117 in CCRCC vs ChRCC, but the sarcomatoid component lost the specificity for these markers (p < 0.05). Patients with positive expressions of CAIX, p53 and Bcl-2 had a poor prognosis.ConclusionsThe sarcomatoid cells in RCC with sarcomatoid differentiation express both epithelial and mesenchymal markers, supporting their epithelial origin. PAX8, CAIX and CD10 could be used as the reliable and useful markers to determine the renal origin of sarcomatoid cells such as in fine needle aspiration cases and metastatic RCC with sarcomatoid differentiation. CAIX, p53 and Bcl-2 might play important roles in the transformation from renal cell carcinoma to high malignant sarcomatoid differentiation, and these three immunohistochemical markers are adverse prognostic factors for the survival of patients with RCC with sarcomatoid differentiation.
Highlights
Renal cell carcinoma (RCC) with sarcomatoid differentiation is a relatively rare tumor containing both carcinoma and sarcomatoid components
PAX8, CAIX and CD10 could be used as the reliable and useful markers to determine the renal origin of sarcomatoid cells such as in fine needle aspiration cases and metastatic RCC with sarcomatoid differentiation
The cohorts could be divided into four groups based on the expression panels of each immunohistochemical markers: carcinoma positive and sarcomatoid cell positive (C+/S+); carcinoma positive and sarcomatoid cell negative (C+/S-); carcinoma negative and sarcomatoid cell positive (C−/S+); carcinoma negative and sarcomatoid cell negative (C−/S-)
Summary
Renal cell carcinoma (RCC) with sarcomatoid differentiation is a relatively rare tumor containing both carcinoma and sarcomatoid components. There has not been a systemic study on immunophenotypes of renal cell carcinoma with sarcomatoid differentiation, especially using some renal specific immunohistochemical markers. According to the 2004 and 2016 WHO Classification of Tumors of the Urinary System and Male Genital Organs, RCC with sarcomatoid differentiation is not recognized as a separate and distinct entity and the sarcomatoid component could arise from the genetic background of any of the RCC subtypes [2]. Due to the low morbidity and the deficiency of study data, the pathogenesis of the transformation from carcinoma to sarcomatoid component along with the prognostic factors for RCC with sarcomatoid differentiation remains unelucidated. This study may shed some light on revealing the pathogenesis and assessing the prognosis of the patients with this relatively rare renal carcinoma
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