Correlation of activated STAT3 expression with clinicopathologic features in lung adenocarcinoma and squamous cell carcinoma.
OBJECTIVE
Signal transducer and activator of transcription (STAT) 3, a member of the STAT family of transcription factors in the Janus kinase (JAK)/STAT signaling pathway, is involved in cell proliferation and apoptosis. STAT3 is activated through phosphorylation (p-STAT3) and is highly expressed in many malignancies. The aims of the present study were to evaluate STAT3 activation (p-STAT3 protein levels) in lung adenocarcinoma and squamous cell carcinoma, and to investigate its correlation with clinicopathologic features of these malignancies.


METHODS
Expression of p-STAT3 was detected by immunohistochemistry in tissue from 127 lung carcinomas (100 adenocarcinomas and 27 squamous cell carcinomas) and 56 normal lungs. Genomic DNA was extracted from frozen patient tissue samples, and key epidermal growth factor receptor (EGFR) mutation sites in exons 18 through 21 of the EGFR gene were amplified and sequenced.


RESULTS
On the basis of the intensity and percentage of p-STAT3 immunoreactivity, samples were divided into negative and positive p-STAT3 expression groups. 103 of these 183 samples (56.3%) showed immunoreactivity for p-STAT3, and this frequency was significantly increased in carcinoma tissue compared with normal tissue (p = 0.001). Positive p-STAT3 expression was detected in 82 of the 127 carcinomas (64.6%) but in only 21 of the 56 normal tissue samples (37.5%). Among the 127 cases of non-small cell lung cancer, p-STAT3 immunoreactivity was significantly correlated with sex (p = 0.004), smoking history (p = 0.006), EGFR mutation status (p = 0.003), clinical stage (p = 0.034), and lymph node metastasis (p = 0.009).


CONCLUSIONS
Our results suggest that p-STAT3 is an important factor during carcinogenesis and metastasis of lung carcinoma, and its relationship to EGFR mutation status may provide potential targeting opportunities in future therapies.
Department of Thoracic Oncology, Tianjin Lung Cancer Center, Tianjin Cancer Institute Hospital, Tianjin Medical University, Tianjin, PR China. jrc_0717@yahoo.com
Richeng
R
Jiang
Ziliang
Z
Jin
Zhujun
Z
Liu
Leina
L
Sun
Liuchun
L
Wang
Kai
K
Li
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D066246:ErbB Receptors / Q000235:genetics; D005091:Exons; D005260:Female; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D050796:STAT3 Transcription Factor / Q000378:metabolism*
D050796:STAT3 Transcription Factor; D066246:ErbB Receptors