Kobayashi Masako, Ooi Akishi, Oda Yoshio, Nakanishi Isao
Department of Molecular and Cellular Pathology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan.
Hum Pathol. 2002 Jan;33(1):21-8. doi: 10.1053/hupa.2002.30185.
We evaluated 173 consecutive breast carcinomas for c-erbB-2 using a combination of immunohistochemistry (IHC) with a commercial polyclonal antibody (Nitirei) and dual-color fluorescence in situ hybridization (FISH) using the c-erbB-2-specific probe and the chromosome 17 centromere-specific probe from Vysis (Downers Grove, IL) and compared the results with the histologic characteristics of intraductal spread, cancer invasion, and intratumoral heterogeneity. With correction for chromosome 17 copy number, c-erbB-2 amplification was observed in 26 tumors (13.5%): high-level amplification in 23 tumors, and low-level amplification in 3. The gene amplification was positively correlated with c-erbB-2 protein overexpression, defined as 2+ or 3+ immunostaining, on a case-by-case basis (P < .000001). All 3+ immunostaining tumors (19 tumors) showed high-level amplification, although gene amplification was found in only 5 of 27 2+ immunostaining tumors. Although the rates of overexpression and gene amplification did not differ in ductal carcinomas in situ and invasive carcinomas (P = .46 and .53, respectively), they were significantly higher in invasive carcinomas with intraductal spreading (P < .0001). Intratumoral heterogeneity of c-erbB-2 amplification was found in only 1 case; however, in 17 invasive carcinomas, intraductal components expressed c-erbB-2 more intensely than invasive components. We conclude that in breast carcinomas, c-erbB-2 overexpression occurs mostly in tumors with high-level gene amplification, and such overexpression appears to endow carcinoma cells with the capacity for intraductal spreading. The best method for detecting breast carcinomas with c-erbB-2 aberrations using archival tissues is to screen cases by IHC; however, follow-up FISH assays are indispensable for excluding false-positive results.
我们使用一种商用多克隆抗体（Nitirei）通过免疫组织化学（IHC）以及使用来自Vysis公司（伊利诺伊州唐纳斯格罗夫）的c-erbB-2特异性探针和17号染色体着丝粒特异性探针进行双色荧光原位杂交（FISH），对173例连续性乳腺癌进行了c-erbB-2评估，并将结果与导管内播散、癌浸润和肿瘤内异质性的组织学特征进行了比较。校正17号染色体拷贝数后，在26例肿瘤（13.5%）中观察到c-erbB-2扩增：23例为高水平扩增，3例为低水平扩增。基因扩增与c-erbB-2蛋白过表达呈正相关，c-erbB-2蛋白过表达在个案基础上定义为免疫染色2+或3+（P <.000001）。所有免疫染色3+的肿瘤（19例）均显示高水平扩增，尽管在27例免疫染色2+的肿瘤中仅5例发现基因扩增。原位导管癌和浸润性癌的过表达率和基因扩增率无差异（分别为P =.46和.53），但在伴有导管内播散的浸润性癌中显著更高（P <.0001）。仅在1例中发现c-erbB-2扩增的肿瘤内异质性；然而，在17例浸润性癌中，导管内成分比浸润成分更强烈地表达c-erbB-2。我们得出结论，在乳腺癌中，c-erbB-2过表达主要发生在具有高水平基因扩增的肿瘤中，并且这种过表达似乎赋予癌细胞导管内播散的能力。使用存档组织检测伴有c-erbB-2异常的乳腺癌的最佳方法是通过IHC筛查病例；然而，后续的FISH检测对于排除假阳性结果是必不可少的。
