Persons D L, Borelli K A, Hsu P H
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City 66160-7232, USA.
Mod Pathol. 1997 Jul;10(7):720-7.
HER-2/neu and c-myc amplification or overexpression have been reported to be associated with poor prognosis in breast carcinoma. The prognostic significance, however, remains somewhat controversial, partly because of discrepancies among different methodologies used for detection of the oncogene amplification or overexpression. Fluorescence in situ hybridization (FISH) has recently been shown to be a useful technique for analyzing genetic alterations in interphase nuclei in various tumors. In this study, FISH was used to quantitate HER-2/ neu and c-myc gene amplification in touch preparations of frozen tissue from 100 node-negative breast carcinomas. HER-2/neu amplification was found to be associated with an abnormal DNA index (P < .001) and tumor size (P < .04). Amplification of c-myc was associated with S phase (P < .0003), abnormal DNA index (P < .003), and a negative estrogen receptor status (P < .01). The coamplification of both oncogenes was strongly associated with an abnormal DNA index (P < .0001) and with tumor size (P < .009). The use of FISH for detection of HER-2/neu gene amplification was 92% concordant with immunocytochemistry (ICC) used for detection of overexpression of HER-2/neu protein. Fifteen of the 100 cases were both amplified for HER-2/neu by FISH and positive by ICC analysis. Seven cases without HER-2/neu gene amplification demonstrated HER-2/neu protein overexpression by ICC. One HER-2/neu-amplified case was negative by ICC. Repeat analysis of a subset of cases showed FISH to be a more reproducible method than ICC in the analysis of HER-2/neu in touch preparations of breast carcinoma. FISH is a rapid and reproducible method that allows the accurate measurement of the level of oncogene amplification within interphase nuclei. The use of FISH should provide a more accurate assessment of the prognostic significance of oncogene amplification in breast carcinoma.
据报道，HER-2/neu和c-myc基因扩增或过表达与乳腺癌预后不良相关。然而，其预后意义仍存在一定争议，部分原因是用于检测癌基因扩增或过表达的不同方法之间存在差异。最近研究表明，荧光原位杂交（FISH）是分析各种肿瘤间期核基因改变的有用技术。本研究采用FISH技术对100例淋巴结阴性乳腺癌冷冻组织的触片标本进行HER-2/neu和c-myc基因扩增定量分析。结果发现，HER-2/neu基因扩增与异常DNA指数（P < 0.001）及肿瘤大小（P < 0.04）相关。c-myc基因扩增与S期（P < 0.0003）、异常DNA指数（P < 0.003）及雌激素受体阴性状态（P < 0.01）相关。两种癌基因的共同扩增与异常DNA指数（P < 0.0001）及肿瘤大小（P < 0.009）密切相关。FISH检测HER-2/neu基因扩增与免疫细胞化学（ICC）检测HER-2/neu蛋白过表达的一致性为92%。100例病例中，15例FISH检测HER-2/neu基因扩增且ICC分析呈阳性。7例无HER-2/neu基因扩增的病例经ICC检测显示HER-2/neu蛋白过表达。1例HER-2/neu基因扩增病例经ICC检测为阴性。对部分病例的重复分析表明，在乳腺癌触片标本HER-2/neu分析中，FISH比ICC更具重复性。FISH是一种快速且可重复的方法，能够准确测量间期核内癌基因扩增水平。FISH的应用应能更准确地评估癌基因扩增在乳腺癌中的预后意义。
