Nakagawa Makoto, Uramoto Hidetaka, Shimokawa Hidehiko, Onitsuka Takamitsu, Hanagiri Takeshi, Tanaka Fumihiro
Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Exp Ther Med. 2011 Jul;2(4):585-590. doi: 10.3892/etm.2011.258. Epub 2011 Apr 26.
Not all patients with lung cancer require postoperative adjuvant chemotherapy after a complete resection. However, no useful markers exist for either selecting appropriate candidates or for predicting clinical recurrence. The purpose of the present study was to clarify the clinical role of insulin-like growth factor receptor-1 (IGFR1) in lung adenocarcinoma. Tumor specimens were collected from 182 patients who underwent a complete resection for adenocarcinoma of the lung. The expression of IGFR1 was evaluated by immunohistochemistry. The genetic status of the epidermal growth factor receptor (EGFR) and K-ras genes was also investigated by PCR-based analyses. Immunohistochemistry and real-time PCR assays were used to evaluate the MET gene association with tyrosine phosphorylation and hepatocyte growth factor (HGF) status, and amplification, respectively. Positive expression of IGFR1 was detected in 43 (23.6%) of the 182 cases. A positive IGFR1 expression was also identified in 12 (42.9%) and 31 (20.1%) of the patients with and without recurrence, respectively (p=0.009). Logistic regression models indicated that positive staining for IGFR1 expression was an independent factor associated with tumor recurrence. IGFR1 expression was associated with a poorer disease-free survival (DFS). Multivariate analysis demonstrated positive IGFR1 expression to be independently associated with an increased risk for poor DFS. The tumors appearing positive for IGFR1 were more frequent among those with K-ras mutations when compared with the wild-type group. IGFR1 expression was associated with reduced DFS correlating with postoperative recurrence. Therefore, the expression status of IGFR1 can be a candidate surrogate marker to select patients who may benefit from adjuvant chemotherapy.
并非所有肺癌患者在完全切除术后都需要进行术后辅助化疗。然而，目前尚无用于选择合适患者或预测临床复发的有效标志物。本研究的目的是阐明胰岛素样生长因子受体-1（IGFR1）在肺腺癌中的临床作用。收集了182例行肺腺癌完全切除术患者的肿瘤标本。通过免疫组织化学评估IGFR1的表达。还通过基于PCR的分析研究了表皮生长因子受体（EGFR）和K-ras基因的基因状态。分别使用免疫组织化学和实时PCR检测评估MET基因与酪氨酸磷酸化和肝细胞生长因子（HGF）状态以及扩增的相关性。182例病例中有43例（23.6%）检测到IGFR1阳性表达。在有复发和无复发的患者中，分别有12例（42.9%）和31例（20.1%）检测到IGFR1阳性表达（p = 0.009）。逻辑回归模型表明，IGFR1表达阳性染色是与肿瘤复发相关的独立因素。IGFR1表达与较差的无病生存期（DFS）相关。多变量分析表明，IGFR1表达阳性与DFS不良风险增加独立相关。与野生型组相比，K-ras突变患者中IGFR1呈阳性的肿瘤更为常见。IGFR1表达与术后复发相关的DFS降低有关。因此，IGFR1的表达状态可以作为选择可能从辅助化疗中获益患者的候选替代标志物。
