Iihara K, Shiozaki H, Tahara H, Kobayashi K, Inoue M, Tamura S, Miyata M, Oka H, Doki Y, Mori T
Department of Surgery II, Osaka University Medical School, Japan.
Cancer. 1993 May 15;71(10):2902-9. doi: 10.1002/1097-0142(19930515)71:10<2902::aid-cncr2820711004>3.0.co;2-j.
The authors recently used immunostaining to demonstrate that patients with epidermal growth factor receptor (EGFR) overexpression have poor survival after surgery. However, the clinical significance of transforming growth factor (TGF)-alpha, one of the ligands of EGFR, has not been demonstrated in esophageal carcinoma.
Immunohistochemical study for TGF-alpha and EGFR was performed on 57 esophageal squamous cell carcinomas using monoclonal antibodies.
TGF-alpha expression was positive in 35% of the tumors, and EGFR overexpression, defined as stronger staining in cancer cells than in normal epithelium, was positive in 43% of the tumors, according to the authors' arbitrary criteria. The incidence of TGF-alpha positivity was relatively higher in patients with the EGFR overexpression (EGFR+) than in the patients with non-overexpression (EGFR-). The survival rate was significantly lower in patients with TGF-alpha(+) than in those with TGF-alpha(-) (P < 0.01) and in patients with EGFR(+) than in patients with EGFR(-) (P < 0.01), respectively. Considering TGF-alpha and EGFR expression simultaneously, the survival rate of the patients with TGF-alpha(+)/EGFR(+) tumors was the lowest of the four subgroups, with statistically significant differences noted. These relationships between the immunoreactivities and survival curves were observed in the analysis within patients with node-positive disease. In addition, a multivariate statistical analysis demonstrated that TGF-alpha was the only significant variable, whereas EGFR and nodal status provided no additional information regarding postoperative survival.
The results presented suggest that TGF-alpha may act as an autocrine growth factor through hyperproducing EGFR and that its expression and EGFR overexpression may prove useful as a valuable prognostic indicator for patients with esophageal carcinoma.
作者最近利用免疫染色法证实，表皮生长因子受体（EGFR）过表达的患者术后生存率较低。然而，转化生长因子（TGF）-α作为EGFR的配体之一，其在食管癌中的临床意义尚未得到证实。
使用单克隆抗体对57例食管鳞状细胞癌进行TGF-α和EGFR的免疫组织化学研究。
根据作者的任意标准，35%的肿瘤中TGF-α表达呈阳性，43%的肿瘤中EGFR过表达（定义为癌细胞染色强于正常上皮）呈阳性。EGFR过表达（EGFR+）患者中TGF-α阳性的发生率相对高于非过表达（EGFR-）患者。TGF-α（+）患者的生存率显著低于TGF-α（-）患者（P<0.01），EGFR（+）患者的生存率显著低于EGFR（-）患者（P<0.01）。同时考虑TGF-α和EGFR的表达，TGF-α（+）/EGFR（+）肿瘤患者的生存率在四个亚组中最低，差异有统计学意义。在对淋巴结阳性疾病患者的分析中观察到了这些免疫反应性与生存曲线之间的关系。此外，多变量统计分析表明，TGF-α是唯一的显著变量，而EGFR和淋巴结状态未提供关于术后生存的额外信息。
所呈现的结果表明，TGF-α可能通过过度产生EGFR而作为一种自分泌生长因子起作用，并且其表达和EGFR过表达可能被证明是食管癌患者有价值的预后指标。
