Kurihara Yasuyuki, Honda Takayuki, Takemoto Akira, Seto Katsutoshi, Endo Satoshi, Tanimoto Kousuke, Kirimura Susumu, Kobayashi Masashi, Baba Shunichi, Nakashima Yasuhiro, Wakejima Ryo, Sakakibara Rie, Ishibashi Hironori, Inazawa Johji, Tanaka Toshihiro, Miyazaki Yasunari, Okubo Kenichi
Department of Thoracic Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Respiratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
JTCVS Open. 2024 Jun 14;20:183-193. doi: 10.1016/j.xjon.2024.06.005. eCollection 2024 Aug.
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.
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 mutations using panel testing, and association studies between mutations and clinical data, including histology and postoperative recurrence, were performed. The association between 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.
Mutations in 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 mutations that were associated with poor relapse-free survival (log-rank test; = .020), whereas patients with lung squamous cell carcinoma histology showed mutations that were not ( = .99). The poor prognosis of mutation-positive LADCs was validated in The Cancer Genome Atlas-LADC cohort (log-rank test; = .0065). Additional immunohistochemistry for p53 in patients with LADC histology in the Tokyo Medical and Dental University cohort showed a significant correlation between mutations and abnormal IHC pattern of p53 (Cramer's correlation coefficient = 0.67).
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.
p53是一种强大的肿瘤抑制基因；其失活促进癌症发生并影响临床结局。然而，p53失活对手术切除的非小细胞肺癌患者早期复发的预后影响仍不清楚。
对东京医科齿科大学170例I至III期原发性肺腺癌（LADC）和肺鳞状细胞癌患者进行了完整切除，通过基因检测筛选p53突变，并进行p53突变与临床数据（包括组织学和术后复发）之间的关联研究。使用来自癌症基因组图谱的604例MSK-IMPACT患者的数据验证p53突变与术后复发之间的关联。对东京医科齿科大学人群的一些亚组进行了额外的p53免疫组织化学检测。
在东京医科齿科大学队列中，经常观察到p53突变（35.9%；170例中有61例）。在组织学分层分析中，LADC组织学患者的p53突变与无复发生存期差相关（对数秩检验；P = 0.020），而肺鳞状细胞癌组织学患者的p53突变则不相关（P = 0.99）。癌症基因组图谱-LADC队列验证了p53突变阳性LADC的不良预后（对数秩检验；P = 0.0065）。东京医科齿科大学队列中LADC组织学患者的额外p53免疫组织化学显示，p53突变与p53异常免疫组化模式之间存在显著相关性（克莱默相关系数 = 0.67）。
p53突变是手术切除LADC预后较差的潜在标志物；p53免疫组织化学可能是识别预后较差的LADC患者的替代方法。
