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CD117 expression in breast phyllodes tumors correlates with adverse pathologic parameters and reduced survival.

乳腺叶状肿瘤中CD117的表达与不利的病理学参数及较差的预后相关

Tan WJ,Thike AA,Tan SY,Tse GM,Tan MH,Bay BH,Tan PH

Abstract

CD117 (c-kit) is a type III receptor tyrosine kinase encoded by the KIT gene. Deregulation of expression and mutations in the gene are implicated in various tumors. Reports of CD117 expression in phyllodes tumors have been controversial. We aim to investigate the protein expression of CD117 and mutations in the KIT gene in phyllodes tumors, and correlate the findings with pathological parameters and clinical outcome. A total of 272 cases were included in this study. CD117 expression was investigated by immunohistochemistry on tissue microarray sections. Toluidine blue staining was performed to indicate mast cells. Overall, 28 (10%) cases were CD117 positive. CD117 expression was significantly associated with tumor grade (P<0.001), increased stromal hypercellularity (P=0.003), stromal atypia (P=0.01), and stromal mitotic activity (P<0.001), permeative microscopic margins (P=0.002), and presence of hemorrhage (P=0.001). Expression was also associated with poorer overall survival (P=0.003). Nineteen cases were further selected for mutation screening through the Affymetrix OncoScan platform. No mutation of the KIT gene was found. Despite a lack of mutations in the KIT gene, CD117 protein expression is associated with unfavorable pathological parameters and poorer prognosis, suggesting an underlying role in the biology of phyllodes tumors.

摘要

CD117 (c-kit)是一种由KIT基因编码的III型受体酪氨酸激酶。在多种肿瘤中都存在这种基因的过量表达及突变。在叶状肿瘤中关于CD117表达水平的报道是有争议的。我们的目的是研究在叶状肿瘤中CD117蛋白表达和KIT基因突变与病理学参数及临床预后的相关性。这项研究共收集了272个病例。CD117表达是通过对组织芯片进行免疫组化染色检测的。甲苯胺蓝染色显示肥大细胞。总结起来,28例(占10%)病例是CD117阳性。CD117表达水平与肿瘤分级 (P<0.001)、间质细胞增生显著(P=0.003)、间质异型性(P=0.01)、间质有丝分裂活性(P<0.001)、微小浸润边缘 (P=0.002)和存在出血(P=0.001)是显著相关的。CD117表达水平也与较差的总生存率相关(P=0.003)。其中的19例通过Affymetrix OncoScan平台进行了基因突变筛查,未发现KIT基因突变。尽管未发现KIT基因突变,CD117蛋白表达水平与不利的病理学参数及较差的预后相关,提示了CD117在叶状肿瘤发病中的潜在的生物学作用。

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