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表皮生长因子受体和转化生长因子α在乳头状和非乳头状肾细胞癌中的表达:与转移行为和预后的相关性

Epidermal growth factor receptor and transforming growth factor alpha expression in papillary and nonpapillary renal cell carcinoma: correlation with metastatic behavior and prognosis.

作者信息

Uhlman D L, Nguyen P, Manivel J C, Zhang G, Hagen K, Fraley E, Aeppli D, Niehans G A

机构信息

Departments of Medicine, Laboratory Medicine and Pathology, Urologic Surgery, and Biostatistics, University of Minnesota, Minneapolis, Minnesota 55455, USA.

出版信息

Clin Cancer Res. 1995 Aug;1(8):913-20.

PMID:9816062
Abstract

Papillary renal carcinomas are a cytogenetically unique subset of renal carcinomas that have been reported to be clinically less aggressive. We have examined 19 papillary tumors for immunohistochemical expression of the epidermal growth factor receptor (EGF-R) and its ligand, transforming growth factor alpha (TGF-alpha). EGF-R and TGF-alpha expression was also studied in 149 nonpapillary tumors and 7 mixed papillary/solid tumors. EGF-R and TGF-alpha expression were compared to histology, stage, metastatic behavior, and survival. Formalin-fixed, paraffin-embedded nephrectomy specimens collected between 1977 and 1986 were stained with antibodies to EGF-R and TGF-alpha. Patients with papillary tumors were found to present with earlier stage disease and had significantly longer survival. Papillary tumors had a significantly lower rate of EGF-R positivity than solid pattern tumors (21% versus 73%, P < 0.001). Intermediate or strong cell membrane immunoreactivity for EGF-R was associated with high tumor grade and poor disease-specific survival. EGF-R positivity in the primary tumor was associated with the presence of metastatic disease and with metastatic spread to lung versus bone. Tumor parenchymal TGF-alpha staining was present in 50% of the cases and was not associated with stage or grade. Unrelated to tumor parenchymal TGF staining, tumor vessels stained for TGF-alpha in 56% of the cases. Vessel TGF-alpha staining was absent in papillary tumors (P < 0.001). The improved clinical behavior of papillary tumors as compared to nonpapillary renal tumors may be related, in part, to their relatively lower levels of EGF-R expression.

摘要

乳头状肾细胞癌是细胞遗传学上独特的一类肾癌,据报道其临床侵袭性较低。我们检测了19例乳头状肿瘤的表皮生长因子受体(EGF-R)及其配体转化生长因子α(TGF-α)的免疫组化表达。还对149例非乳头状肿瘤和7例乳头状/实性混合肿瘤进行了EGF-R和TGF-α表达研究。将EGF-R和TGF-α表达与组织学、分期、转移行为及生存率进行了比较。对1977年至1986年间收集的福尔马林固定、石蜡包埋的肾切除标本用抗EGF-R和TGF-α抗体进行染色。发现乳头状肿瘤患者疾病分期较早,生存期显著更长。乳头状肿瘤的EGF-R阳性率显著低于实性肿瘤(21%对73%,P<0.001)。EGF-R呈中度或强细胞膜免疫反应与肿瘤高分级及较差的疾病特异性生存率相关。原发性肿瘤中EGF-R阳性与转移疾病的存在以及肺转移而非骨转移相关。50%的病例肿瘤实质有TGF-α染色,且与分期或分级无关。与肿瘤实质TGF染色无关,56%的病例肿瘤血管有TGF-α染色。乳头状肿瘤中无血管TGF-α染色(P<0.001)。与非乳头状肾肿瘤相比,乳头状肿瘤较好的临床行为可能部分与其相对较低水平的EGF-R表达有关。

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