Open AccessAccumulation of p62/ SQSTM 1 is associated with poor prognosis in patients with lung adenocarcinoma
Author(s) -
Inoue Daisuke,
Suzuki Takashi,
Mitsuishi Yoichiro,
Miki Yasuhiro,
Suzuki Satoshi,
Sugawara Shunichi,
Watanabe Mika,
Sakurada Akira,
Endo Chiaki,
Uruno Akira,
Sasano Hironobu,
Nakagawa Takayuki,
Satoh Kennichi,
Tanaka Nobuyuki,
Kubo Hiroshi,
Motohashi Hozumi,
Yamamoto Masayuki
Publication year - 2012
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2012.02216.x
Subject(s) - adenocarcinoma , immunohistochemistry , lung cancer , medicine , pathology , oncology , carcinoma , histology , cancer , lung , pathological , cancer research
p62/ SQSTM 1 is a selective substrate of autophagy, and aberrant accumulation of p62 has been observed in various pathological conditions. To understand the roles p62 plays in non‐small‐cell lung cancer ( NSCLC ), we carried out immunohistochemical analyses of p62 expression in a cohort of patients with annotated clinicopathological data. As analyses of murine and human hepatocellular carcinomas suggested a correlation between p62 and Nrf2 accumulations, we also examined NRF 2 expression in the same cohort. The expression of NRF 2 and p62 was examined by immunohistochemical methods in 109 NSCLC cases, which included patients with adenocarcinoma ( n = 72), squamous cell carcinoma ( n = 31), and large cell carcinoma ( n = 6). Accumulation of NRF 2 and p62 was detected in 34% and 37% of NSCLC patients, respectively. The accumulations of p62 and NRF 2 did not correlate with each other, but both were associated with worse lung cancer‐specific survival ( P = 0.0003 for NRF 2; P = 0.0130 for p62). NRF 2 status had an impact on NSCLC prognosis irrespective of histology types, but p62 status did so particularly in adenocarcinoma ( P = 0.037). Multivariate analysis indicated that positive immunoreactivities of NRF 2 and p62 were both independent factors predicting worse lung cancer‐specific survival ( P < 0.0001 for NRF 2 and P = 0.04 for p62). This study revealed that both NRF 2 and p62 are independent prognostic factors for NSCLC . The prognostic impact of p62 status was pronounced in adenocarcinoma patients, suggesting that molecular mechanisms underlying cancer evolution differ between adenocarcinoma and squamous cell carcinoma. ( Cancer Sci 2012; 103: 760–766)