Kapitanović S, Radosević S, Kapitanović M, Andelinović S, Ferencić Z, Tavassoli M, Primorać D, Sonicki Z, Spaventi S, Pavelic K, Spaventi R
Division of Molecular Medicine, Ruder Bosković Institute, Zagreb, Croatia.
Gastroenterology. 1997 Apr;112(4):1103-13. doi: 10.1016/s0016-5085(97)70120-3.
BACKGROUND & AIMS: HER-2/neu oncogene encodes a transmembrane tyrosine kinase receptor that is amplified and/or overexpressed predominantly in adenocarcinomas. This phenomenon has been most intensively studied in breast carcinoma where its amplification and overexpression correlate with the overall course of disease and poor prognosis. This study was designed to investigate HER-2/neu gene expression in benign and malignant colorectal lesions and to evaluate its prognostic importance in colorectal cancer.
Two hundred twenty-one samples of normal colon, benign lesions, and colorectal adenocarcinomas were studied for expression of HER-2/neu oncoprotein. Immunohistochemical staining of formalin-fixed, paraffin-embedded tissue sections of primary tumor and lymph nodes was performed. Immunoprecipitation followed by Western blotting of freshly frozen samples of the same tumors were also performed.
Normal colon mucosa, benign lesions, and adenocarcinomas clearly differed in the expression levels and histological distribution of p185(HER-2/neu). Normal mucosa was mostly negative, but significant number of benign lesions and adenocarcinomas overexpressed HER-2/neu protein. Adenocarcinomas were significantly more positive than benign lesions. The results show significant correlation with the epithelial abnormality degree and clinical parameters including Dukes' classification and relapse-free and postoperative survival period.
The p185(HER-2/neu) rate expression could serve as an independent prognostic factor in patients with p185(HER-2/neu)-positive colorectal malignancies.
HER-2/neu癌基因编码一种跨膜酪氨酸激酶受体，该受体主要在腺癌中扩增和/或过度表达。这种现象在乳腺癌中得到了最深入的研究，其扩增和过度表达与疾病的总体进程及不良预后相关。本研究旨在调查HER-2/neu基因在良性和恶性结直肠病变中的表达情况，并评估其在结直肠癌中的预后重要性。
对221份正常结肠、良性病变及结直肠腺癌样本进行HER-2/neu癌蛋白表达研究。对原发性肿瘤和淋巴结的福尔马林固定、石蜡包埋组织切片进行免疫组织化学染色。还对相同肿瘤的新鲜冷冻样本进行免疫沉淀后再进行蛋白质印迹分析。
正常结肠黏膜、良性病变及腺癌在p185(HER-2/neu)的表达水平和组织学分布上明显不同。正常黏膜大多为阴性，但相当数量的良性病变和腺癌过度表达HER-2/neu蛋白。腺癌的阳性率明显高于良性病变。结果显示与上皮异常程度以及包括Dukes分期、无复发生存期和术后生存期在内的临床参数显著相关。
p185(HER-2/neu)表达率可作为p185(HER-2/neu)阳性结直肠恶性肿瘤患者的独立预后因素。
