Yu Wenjuan, Wang Yuewei, Jiang Yanxia, Zhang Wei, Li Yujun
Department of Pathology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China.
Department of Vascular Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China.
BMC Cancer. 2017 Apr 27;17(1):293. doi: 10.1186/s12885-017-3275-8.
Renal 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.
A 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.
Histologically, 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.
The 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.
伴有肉瘤样分化的肾细胞癌（RCC）是一种相对罕见的肿瘤，同时包含癌和肉瘤样成分。然而，目前尚未有关于伴有肉瘤样分化的肾细胞癌免疫表型的系统性研究，尤其是使用一些肾脏特异性免疫组化标志物的研究。在本研究中，我们旨在全面研究伴有肉瘤样分化的RCC的独特免疫表型，以分析肉瘤样分化的发病机制，并确定伴有肉瘤样分化的RCC的新预后因素。
共纳入42例伴有肉瘤样分化的RCC病例进行研究。在组织芯片上进行免疫组化研究，以评估19种免疫组化标志物的表达，包括一系列上皮、间充质标志物和RCC特异性标志物。应用Kaplan-Meier法评估CD10、CAIX、p53和Bcl-2的预后价值。
组织学上，42例伴有肉瘤样分化的RCC呈现出不同比例的癌和肉瘤样成分。根据癌成分，该队列包括35例透明细胞肾细胞癌（CCRCC）和7例嫌色肾细胞癌（ChRCC）。免疫组化方面，所有病例波形蛋白均呈阳性，80%的病例至少对一种上皮标志物呈免疫染色，如CK、EMA、CK7和CK18。值得注意的是，肉瘤样细胞中CAIX、CD10和PAX8的表达率分别为76%、76%和64%。CCRCC与ChRCC肿瘤的癌成分对CAIX、CD10、波形蛋白、CK7和CD117显示出不同的标记，但肉瘤样成分对这些标志物失去了特异性（p<0.05）。CAIX、p53和Bcl-2表达阳性的患者预后较差。
伴有肉瘤样分化的RCC中的肉瘤样细胞同时表达上皮和间充质标志物，支持其上皮起源。PAX8、CAIX和CD10可作为确定肉瘤样细胞肾起源的可靠且有用的标志物，如在细针穿刺病例和伴有肉瘤样分化的转移性RCC中。CAIX、p53和Bcl-2可能在肾细胞癌向高恶性肉瘤样分化的转变中起重要作用，这三种免疫组化标志物是伴有肉瘤样分化的RCC患者生存的不良预后因素。
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