Immunohistochemical profiling of receptor tyrosine kinases, MED 12 and TGF-βRII of surgically resected small cell lung cancer, and the potential of c-kit as a prognostic marker

Hiroshi Yokouchi, Hiroshi Nishihara, Toshiyuki Harada, Takashi Ishida, Shigeo Yamazaki, Hajime Kikuchi, Satoshi Oizumi, Hidetaka Uramoto, Fumihiro Tanaka, Masao Harada, Kenji Akie, Fumiko Sugaya, Yuka Fujita, Kei Takamura, Tetsuya Kojima, Mitsunori Higuchi, Osamu Honjo, Yoshinori Minami, Naomi Watanabe, Aya GotoHiroyuki Suzuki, Hirotoshi D. Dosaka-Akita, Hiroshi Isobe, Masaharu Nishimura, Mitsuru Munakata

研究成果: Article査読

12 被引用数 (Scopus)

抄録

The limited number of available treatments for patients with small-cell lung cancer (SCLC) has prompted us to further investigate the biology of SCLC by molecular profiling. We collected formalin-fixed paraffin-embedded tumor samples from 127 patients with SCLC, who had undergone surgery at 16 institutions between January 2003 and January 2013, and analyzed the association between disease-specific survival and protein expression of c-kit, c-Met, epidermal growth factor receptor, human EGFR-related 2, vascular endothelial growth factor receptor II, anaplastic lymphoma kinase, mediator complex subunit 12 (MED12), and transforming growth factor beta receptor II (TGF-βRII) by immunohistochemistry (IHC). Of the 125 evaluable samples, all tumors expressed MED12, and 123 samples (98.4%) expressed TGF-βRII. MED12 was highly expressed in the nucleus in 92% of the positive samples while TGF-βRII was highly expressed in the cytoplasm in 55% of the positive samples. High c-kit expression was an independent favorable prognostic marker confirmed by multivariate analysis (hazard ratio: 0.543, 95% confidence interval: 0.310-0.953, p = 0.033). Both the relapse free-survival and overall survival of patients who underwent adjuvant chemotherapy were statistically longer in those with high c-kit expression (n = 38) than those with intermediate, low, or no c-kit expression (n = 19) (not reached vs 11.6 months, p = 0.021; not reached vs 25.9 months, p = 0.028). IHC for c-kit may offer a prognostic marker for early-stage SCLC, and the results for MED12 and TGF- βRII may suggest the biological characteristics of SCLC. Further investigation of the roles of their related molecules in early stage SCLC is required.

本文言語English
ページ(範囲)39711-39726
ページ数16
ジャーナルOncotarget
8
24
DOI
出版ステータスPublished - 2017
外部発表はい

ASJC Scopus subject areas

  • 腫瘍学

フィンガープリント

「Immunohistochemical profiling of receptor tyrosine kinases, MED 12 and TGF-βRII of surgically resected small cell lung cancer, and the potential of c-kit as a prognostic marker」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル