PICT1 expression is a poor prognostic factor in non-small cell lung cancer
Kyoko Okamura1, Koichi Takayama1, Kohichi Kawahara2,3, Taishi Harada1, Miki Nishio3, Kohei Otsubo1,3, Kayo Ijichi1,4, Mikihiro Kohno5, Eiji Iwama1,6, Akiko Fujii1, Keiichi Ota1, Takaomi Koga4, Tatsuro Okamoto5, Akira Suzuki3, Yoichi Nakanishi1
1 Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Japan.
2 Department of Molecular Oncology, Graduate School of Medical and Dental Science, Kagoshima University, Japan.
3 Division of Cancer Genetics, Medical Institute of Bioregulation, Kyushu University, Japan.
4 Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Japan.
5 Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Japan.
6 Faculty of Medical Sciences, Department of Comprehensive Clinical Oncology, Kyushu University, Japan.
Koichi Takayama, email:
Keywords: PICT1; TP53; lung cancer; lymphatic invasion; GLTSCR2
Received: March 19, 2014 Accepted: May 25, 2014 Published: May 25, 2014
PICT1 is a key regulator of the MDM2–TP53 pathway. High mRNA expression levels of PICT1 are associated with poor prognosis in several cancers with wild-type TP53. In this study, we identified the PICT1 protein expression profile in non-small cell lung cancer (NSCLC) with wild-type TP53 in the nucleolus and cytoplasm, and revealed the relationship between PICT1 expression and patient clinicopathological factors. PICT1 expression in the tumor cells of 96 NSCLC patients with wild-type TP53 was evaluated by immunohistochemistry. Forty-three of 96 (44.8%) NSCLC samples were positive for nucleolar PICT1, while 40/96 (41.7%) NSCLC samples were positive for cytoplasmic PICT1. There was no correlation between nucleolar PICT1 expression and clinicopathological factors. However, cytoplasmic PICT1 expression was significantly correlated with sex, smoking history, differentiation, lymphatic invasion and pathological stage. In multivariate analysis, lymphatic invasion was significantly associated with cytoplasmic PICT1 expression (hazard ratio: 5.02, P = 0.026). We scrutinized PICT1 expression in samples of NSCLC with wild-type TP53, and showed a correlation between cytoplasmic PICT1 expression and several clinicopathological factors in these patients. Our results indicate that cytoplasmic PICT1 expression is a poor prognostic factor and is associated with tumor progression via lymphatic invasion in these patients.