Prognostic significance of OCT4 expression in adenocarcinoma of the lung.
OBJECTIVE
The purpose of this study was to detect the presence of cancer stem-like cells with bronchioalveolar stem cells (BASCs) properties and investigate the clinicopathological role of expression of OCT4 as well as the correlation with clinical outcomes in adenocarcinoma of the lung.


METHODS
Specimens of 112 cases of Stage IB-IIIA lung adenocarcinoma after radical surgery were collected from June 1999 to June 2002. The putative cancer stem cells in tumor sections were visualized immunofluorescently by using the antibodies against three bronchioalveolar stem cells markers: surfactant protein C (SPC), Clara cell secretary protein (CCSP) and Octamer-4 (OCT4). Cancer stem-like cells with bronchioalveolar stem cell properties in human lung adenocarcinoma were subdivided into two phenotypes: OCT4(+)BASC (SPC(+)CCSP(+)OCT4(+)) and OCT4(-)BASC (SPC(+)CCSP(+)OCT4(-)).


RESULTS
Cancer cells with CCSP(+)SPC(+)BASC phenotype were detected in 107 cases, 80 cases with OCT4(+)BASC phenotype (SPC(+)CCSP(+)OCT4(+)) and 27 cases with SPC(+)CCSP(+)OCT4(-). There was a correlation between differentiation and OCT4 expression (P = 0.047). The pattern of survival curves shows the expected trend of decreasing survival with increasing stage at diagnosis (P = 0.015) and with OCT4(+)BASC expression (P = 0.019). Multivariate Cox's analysis reveals that pathological stages of TNM (P = 0.008) and bronchioalveolar stem cells phenotypes (P = 0.015) are the independent prognostic factors.


CONCLUSIONS
The cancer cells with bronchioalveolar stem cells phenotype are detectable in adenocarcinoma of the lung and the expression of self-renewal regulatory gene OCT4 in these cells indicated the worse clinical outcomes.
Zhang
Xueyan
X
Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, No 241, West Huaihai Rd, Shanghai 200030, People's Republic of China.
Han
Baohui
B
Huang
Jinsu
J
Zheng
Biqiang
B
Geng
Qin
Q
Aziz
Fahad
F
Dong
Qianggang
Q
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002945:Cisplatin; D005260:Female; D005455:Fluorescent Antibody Technique / Q000706:statistics & numerical data; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D037721:Pulmonary Surfactant-Associated Protein C / Q000378:metabolism; D014598:Uteroglobin / Q000378:metabolism; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D055815:Young Adult
D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D037721:Pulmonary Surfactant-Associated Protein C; C556389:SCGB1A1 protein, human; D014747:Vinblastine; D014598:Uteroglobin; D002945:Cisplatin; D000077235:Vinorelbine