Immunohistochemistry of p53 surrogates TP53 mutation as an accurate predictor for early-relapse of surgically resected stage I-III lung adenocarcinomaCentral MessagePerspective
Yasuyuki Kurihara, MD,
Takayuki Honda, MD, PhD,
Akira Takemoto, MD, PhD,
Katsutoshi Seto, MD, PhD,
Satoshi Endo, MD,
Kousuke Tanimoto, MD, PhD,
Susumu Kirimura, MD, PhD,
Masashi Kobayashi, MD, PhD,
Shunichi Baba, MD, PhD,
Yasuhiro Nakashima, MD, PhD,
Ryo Wakejima, MD, PhD,
Rie Sakakibara, MD, PhD,
Hironori Ishibashi, MD, PhD,
Johji Inazawa, MD, PhD,
Toshihiro Tanaka, MD, PhD,
Yasunari Miyazaki, MD, PhD,
Kenichi Okubo, MD, PhD
Affiliations
Yasuyuki Kurihara, MD
Department of Thoracic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
Takayuki Honda, MD, PhD
Department of Respiratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Akira Takemoto, MD, PhD
Bioresource Research Center, Tokyo Medical and Dental University, Tokyo, Japan
Katsutoshi Seto, MD, PhD
Department of Thoracic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
Satoshi Endo, MD
Department of Respiratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Kousuke Tanimoto, MD, PhD
Research Core, Tokyo Medical and Dental University, Tokyo, Japan
Susumu Kirimura, MD, PhD
Department of Pathology, Tokyo Medical and Dental University, Tokyo, Japan
Masashi Kobayashi, MD, PhD
Department of Thoracic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
Shunichi Baba, MD, PhD
Department of Thoracic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
Yasuhiro Nakashima, MD, PhD
Department of Thoracic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
Ryo Wakejima, MD, PhD
Department of Thoracic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
Rie Sakakibara, MD, PhD
Department of Respiratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Hironori Ishibashi, MD, PhD
Department of Thoracic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
Johji Inazawa, MD, PhD
Research Core, Tokyo Medical and Dental University, Tokyo, Japan
Toshihiro Tanaka, MD, PhD
Bioresource Research Center, Tokyo Medical and Dental University, Tokyo, Japan
Yasunari Miyazaki, MD, PhD
Department of Respiratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Kenichi Okubo, MD, PhD
Department of Thoracic Surgery, Tokyo Medical and Dental University, Tokyo, Japan; Address for reprints: Kenichi Okubo, MD, PhD, Department of Thoracic Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Introduction: TP53 is a strong tumor suppressor gene; its deactivation contributes to carcinogenesis and influences clinical outcomes. However, the prognostic influence of p53 deactivation on early relapse in patients with surgically resected non–small cell lung cancer remains unclear. Materials and methods: A cohort of 170 patients with primary stage I through III lung adenocarcinoma (LADC) and lung squamous cell carcinoma who underwent complete resection at Tokyo Medical and Dental University was screened for TP53 mutations using panel testing, and association studies between TP53 mutations and clinical data, including histology and postoperative recurrence, were performed. The association between TP53 mutations and postoperative recurrence was validated using data from 604 patients with MSK-IMPACT from The Cancer Genome Atlas. Additional immunohistochemistry for p53 was performed on some subsets of the Tokyo Medical and Dental University population. Results: Mutations in TP53 were recurrently observed (35.9%; 61 out of 170) in the Tokyo Medical and Dental University cohort. In the histology-stratified analysis, patients with LADC histology showed TP53 mutations that were associated with poor relapse-free survival (log-rank test; P = .020), whereas patients with lung squamous cell carcinoma histology showed TP53 mutations that were not (P = .99). The poor prognosis of TP53 mutation-positive LADCs was validated in The Cancer Genome Atlas-LADC cohort (log-rank test; P = .0065). Additional immunohistochemistry for p53 in patients with LADC histology in the Tokyo Medical and Dental University cohort showed a significant correlation between TP53 mutations and abnormal IHC pattern of p53 (Cramer's correlation coefficient V = 0.67). Conclusions: TP53 mutation is a potential marker for worse prognosis in surgically resected LADC; immunohistochemistry for p53 could be a surrogate method to identify patients with LADC with a worse prognosis.
