Molecular Diagnostics

British Journal of Cancer (2008) 98, 596–603. doi:10.1038/sj.bjc.6604197 www.bjcancer.com
Published online 22 January 2008

Proteomic analysis of stage I primary lung adenocarcinoma aimed at individualisation of postoperative therapy

J Maeda1, T Hirano1, A Ogiwara2,3, S Akimoto2,3, T Kawakami2, Y Fukui4, T Oka4, Y Gong1, R Guo1, H Inada1, K Nawa1, M Kojika1, Y Suga1, T Ohira1, K Mukai5 and H Kato1

  1. 1Department of Surgery, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan
  2. 2Clinical Proteome Center, Tokyo Medical University, 2-6-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 163-0217, Japan
  3. 3Medical ProteoScope Co. Ltd, 2-6-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 163-0217, Japan
  4. 4Taiho Pharmaceutical Co. Ltd, Tokyo, Japan
  5. 5Department of Pathology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan

Correspondence: Dr T Hirano, E-mail: thirano@tokyo-med.ac.jp

Received 10 August 2007; Revised 22 November 2007; Accepted 18 December 2007; Published online 22 January 2008.

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Abstract

Although postoperative adjuvant chemotherapy (PAC) with uracil–tegafur significantly improves the prognosis of patients with stage I lung adenocarcinoma, subset analysis has revealed that only 11.5% of patients with stage IB derive actual benefit from such therapy. Therefore, it is extremely important to identify patients for whom adjuvant chemotherapy will be beneficial. We performed comprehensive protein analysis of 24 surgically resected specimens of stage I adenocarcinoma using liquid chromatography-tandem mass spectrometry (LC-MS/MS), followed by bioinformatical investigations to identify protein molecules. Furthermore, we carried out immunohistochemical studies of 90 adenocarcinoma specimens to validate the results of LC-MS/MS. We detected two kinds of protein molecules (myosin IIA and vimentin) by LC-MS/MS. We confirmed their immunohistochemical expression and distribution, and evaluated the relationship between the expression of these proteins and prognosis after adjuvant chemotherapy. Patients with no expression of either myosin IIA or vimentin showed a significantly better outcome regardless of PAC using uracil–tegafur. However, we were unable to select responders to uracil–tegafur using these proteins. Cases of adenocarcinoma lacking expression of either myosin IIA or vimentin show a good outcome without PAC, and therefore do not require such treatment.

Keywords:

myosin IIA, vimentin, postoperative adjuvant chemotherapy, responder to uracil–tegafur, stage I lung adenocarcinoma