Gramlich T L, Cohen C, Fritsch C, DeRose P B, Gansler T
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia.
Am J Clin Pathol. 1994 Apr;101(4):493-9. doi: 10.1093/ajcp/101.4.493.
Previous studies have found that amplification and overexpression of the c-erbB-2 oncogene in mammary ductal adenocarcinomas predicts decreased disease-free or overall survival. Information regarding the prognostic and pathogenetic significance of oncogene amplification has been limited by difficulty obtaining sufficient quantities of high molecular weight DNA for Southern blot analysis. Differential polymerase chain reaction (PCR) has been suggested as an alternative method for evaluating gene amplification and can be performed using formalin-fixed paraffin-embedded specimens. The authors of this study used differential PCR to detect c-erbB-2 gene amplification and immunohistochemistry to evaluate c-erbB-2 expression. A highly significant degree of concordance (P < .002) between c-erbB-2 amplification and expression was observed. Abnormalities of c-erbB-2 copy number or expression were more common in tumors with higher histologic grade, and trends were noted toward association with other prognostically unfavorable biologic markers, such as reduced progesterone receptor content and DNA aneuploidy.
以往的研究发现,乳腺导管腺癌中c-erbB-2癌基因的扩增和过表达预示着无病生存期或总生存期缩短。由于难以获得足够量的高分子量DNA用于Southern印迹分析,有关癌基因扩增的预后和发病机制意义的信息一直有限。差异聚合酶链反应(PCR)已被建议作为评估基因扩增的替代方法,并且可以使用福尔马林固定石蜡包埋的标本进行。本研究的作者使用差异PCR检测c-erbB-2基因扩增,并使用免疫组织化学评估c-erbB-2表达。观察到c-erbB-2扩增与表达之间存在高度显著的一致性(P <.002)。c-erbB-2拷贝数或表达异常在组织学分级较高的肿瘤中更为常见,并且注意到与其他预后不良的生物学标志物相关的趋势,例如孕酮受体含量降低和DNA非整倍体。