Ueda Shigeto, Hatsuse Kazuo, Tsuda Hitoshi, Ogata Sho, Kawarabayashi Nobuaki, Takigawa Toshimichi, Einama Takahiro, Morita Daisaku, Fukatsu Kazuhiko, Sugiura Yoshiaki, Matsubara Osamu, Mochizuki Hidetaka
Department of Surgery I, National Defense Medical College, Tokorozawa, Saitama, Japan.
Mod Pathol. 2006 Jun;19(6):788-96. doi: 10.1038/modpathol.3800582.
The insulin-like growth factor receptor type 1 (IGF1R) and epidermal growth factor receptor (EGFR) are reportedly overexpressed in pancreatic cancer. However, the correlation between activated EGFR and IGF1R and their clinicopathological implications still remain unclear. The cellular localization and overexpression of IGF1R and EGFR were investigated immunohistochemically in primary invasive ductal pancreatic carcinomas obtained from 74 patients who underwent radical surgical resection. We also compared the status of IGF1R and EGFR overexpression between primary tumors and hepatic metastatic tumors obtained from 44 autopsied patients. Among the 74 surgically resected primary tumors, cytoplasm- and membrane-dominant EGFR overexpression was detected in 22 (30%) and 7 (9%), respectively, whereas cytoplasm- and membrane-dominant IGF1R overexpression was detected in 8 (11%) and 28 (38%), respectively. Membrane-dominant EGFR and cytoplasm-dominant IGF1R were more frequent in lower-grade tumors and correlated with favorable prognosis, whereas cytoplasm-dominant EGFR and membrane-dominant IGF1R were more frequent in higher-grade tumors and correlated with poor prognosis. In 36 autopsy specimens of pancreatic tumor with concurrent overexpression of IGF1R and EGFR, there was an inverse correlation between the IGF1R and EGFR localization patterns (P = 0.001). In the hepatic metastatic tumors obtained by autopsy, the incidences of both IGF1R and EGFR overexpression were much higher than in the surgically resected primary tumors. More than half of the autopsy cases consistently showed membrane-dominant EGFR expression in both the primary tumor and hepatic metastases, whereas IGF1R expression showed considerable variation. Crosstalk between differently localized IGF1R and EGFR might play a role in determining the biological aggressiveness of pancreatic cancer, although their cellular localization may often alter during the process of metastasis.
据报道，胰岛素样生长因子1型受体（IGF1R）和表皮生长因子受体（EGFR）在胰腺癌中过表达。然而，激活的EGFR和IGF1R之间的相关性及其临床病理意义仍不清楚。我们采用免疫组织化学方法研究了74例接受根治性手术切除的原发性浸润性导管胰腺癌中IGF1R和EGFR的细胞定位及过表达情况。我们还比较了44例尸检患者的原发性肿瘤和肝转移瘤中IGF1R和EGFR过表达的情况。在74例手术切除的原发性肿瘤中，分别有22例（30%）和7例（9%）检测到细胞质和膜为主的EGFR过表达，而分别有8例（11%）和28例（38%）检测到细胞质和膜为主的IGF1R过表达。膜为主的EGFR和细胞质为主的IGF1R在低级别肿瘤中更常见，且与良好预后相关，而细胞质为主的EGFR和膜为主的IGF1R在高级别肿瘤中更常见，且与不良预后相关。在36例IGF1R和EGFR同时过表达的胰腺肿瘤尸检标本中，IGF1R和EGFR定位模式之间存在负相关（P = 0.001）。在尸检获得的肝转移瘤中，IGF1R和EGFR过表达的发生率均远高于手术切除的原发性肿瘤。超过一半的尸检病例在原发性肿瘤和肝转移瘤中均持续显示膜为主的EGFR表达，而IGF1R表达则有相当大的差异。不同定位的IGF1R和EGFR之间的相互作用可能在决定胰腺癌的生物学侵袭性方面发挥作用，尽管它们的细胞定位在转移过程中可能经常发生改变。
