The Significance of BerEp4 and Cytokeratin 19 Expressions in Epithelial Tumors of Kidney and Renal Pelvis

A. Ozcan, I. Yavan, Melih Kılınç, S. Uğuz, Ş. Ozaydin
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Abstract

Objective: The differential diagnosis in the epithelial tumors of kidney and renal pelvis can be problematic due to their overlapping morphologic features. This is much more complicated in some conditions, such as renal oncocytoma (RO) vs chromophobe renal cell carcinoma (ChRCC) and renal cell carcinoma (RCC) vs urothelial carcinoma of renal pelvis (UC-RP). The purpose of this study was to assess potential contributions of BerEP4 and cytokeratin 19 (CK19) expressions in the differential diagnosis of these challenging cases. Methods: A total 57 cases consisted of 11 chromophobe (ChRCC), 18 clear cell (CCRCC), 12 papillary (PRCC), and 2 unclassified RCCs, 1 multilocular cystic renal cell neoplasm (MCRCN) with low malignant potential, 7 UC-RP, and 6 renal oncocytomas (RO) were stained against BerEp4 and CK19 antibodies using automated immunostainer. Results: All ROs demonstrated membranous BerEP4 expression, but no CK19 expression. Unlike ROs, most ChRCCs exhibited diffuse and strong CK19 expression, but no or focal and weak BerEP4 expression. This distinctive opposite expression pattern was highlighted in hybrid oncocytic chromophobe tumor (HOCT). CCRCCs showed highly variable expression patterns for both markers. PRCC type 1 tumors demonstrated diffuse and strong BerEp4 and CK19 expressions. PRCC type 2 exhibited BerEP4 and CK19 expressions, but their expressions were focal and weaker than for PRCC type 1. MCRCN demonstrated diffuse and strong BerEP4 expression, but no expression for CK19 unlike cystic CCRCC, which is strongly positive for both markers. Epithelioid cells in unclassified RCC showed strong CK19 and weak BerEP4 expression, whereas spindle cells in the tumor did not express CK19 and BerEp4 or exhibited scattered and weak expressions. UC-RP showed diffuse and strong CK19 expression, but no or scattered BerEP4expression was seen in the tumor. We also evaluated CK19 and BerEP4 expression in non-neoplastic adjacent kidney and renal pelvis. Conclusion: This study revealed that 1) BerEP4 and CK19 exhibit variable and distinctive immunoprofiles in epithelial tumors of kidney and renal pelvis, 2) an immunoprofile of BerEP4 (+)/CK19 (-) favors RO in contrast to an opposite profile for ChRCC, 3) The heterogeneous expressions of BerEP4 and CK19 in low grade RCC with eosinophilic cytoplasm favors HOCT, 4) PRCC type 1 strongly express both biomarkers, and 5) although RCC subtypes express CK19 in a variable proportion and intensity, diffuse and strong CK19 expression favors UC-RP.
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肾和肾盂上皮肿瘤中BerEp4和细胞角蛋白19表达的意义
目的:肾脏和肾盂上皮性肿瘤由于其形态特征重叠而难以鉴别诊断。在某些情况下,这要复杂得多,例如肾嗜铬细胞瘤(RO)与憎色性肾细胞癌(ChRCC)和肾细胞癌(RCC)与肾盂尿路上皮癌(UC-RP)。本研究的目的是评估BerEP4和细胞角蛋白19 (CK19)表达在这些挑战性病例鉴别诊断中的潜在贡献。方法:采用自动免疫染色法对57例患者进行BerEp4和CK19抗体染色,其中11例为疏色细胞瘤(ChRCC), 18例为透明细胞瘤(CCRCC), 12例为乳头状细胞瘤(PRCC), 2例为未分类的rcc, 1例为低恶性潜能的多室囊性肾细胞瘤(MCRCN), 7例为UC-RP, 6例为肾癌细胞瘤(RO)。结果:所有ROs均膜性表达BerEP4,未表达CK19。与ROs不同,大多数chrcc表现出弥漫性和强表达CK19,但不表达或局灶性和弱表达BerEP4。这种独特的相反表达模式在混合型嗜癌细胞憎色肿瘤(HOCT)中得到了突出表现。ccrcc在两种标记物的表达模式上都表现出高度可变。PRCC 1型肿瘤表现为弥漫性、强表达BerEp4和CK19。PRCC 2型表现出BerEP4和CK19的表达,但与PRCC 1型相比,BerEP4和CK19的表达是局灶性的、弱的。mccrcn表现出弥漫性和强烈的BerEP4表达,但CK19不表达,不像囊性CCRCC,这两种标志物都强烈阳性。未分类的RCC上皮样细胞CK19和BerEP4表达较强,而肿瘤梭形细胞不表达CK19和BerEP4或表现为分散和弱表达。UC-RP中CK19呈弥漫性强表达,而berep4未见或分散表达。我们还评估了CK19和BerEP4在非肿瘤邻近肾和肾盂中的表达。结论:本研究表明:1)BerEP4和CK19在肾脏和肾盂上皮肿瘤中表现出不同的、独特的免疫谱;2)BerEP4 (+)/CK19(-)的免疫谱有利于RO,而在ChRCC中则相反;3)BerEP4和CK19在具有嗜酸性细胞质的低级别RCC中异质表达有利于HOCT; 4) PRCC 1型强烈表达这两种生物标志物;弥漫和强表达的CK19有利于UC-RP。
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