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Expression of activated signal transducer and activator of transcription 3 predicts poor clinical outcome in gastric adenocarcinoma
Author(s) -
LEE JEEYUN,
KANG WON KI,
PARK JOON OH,
PARK SE HOON,
PARK YOUNG SUK,
LIM HO YEONG,
KIM JUNGA,
KONG JEEHYUN,
CHOI MIN GEW,
SOHN TAE SUNG,
NOH JAE HYUNG,
BAE JAE MOON,
KIM SUNG,
LIM DO HOON,
KIM KYOUNGMEE,
PARK CHEOL KEUN
Publication year - 2009
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/j.1600-0463.2009.02512.x
Subject(s) - stat3 , immunohistochemistry , stat protein , survivin , medicine , cancer research , adenocarcinoma , cancer , pathology , oncology , biology , signal transduction , biochemistry
Lee J, Kang WK, Park JO, Park SH, Park YS, Lim HY, Kim J, Kong J, Choi MG, Sohn TS, Noh JH, Bae JM, Kim S, Lim DH, Kim K‐M, Park CK. Expression of activated signal transducer and activator of transcription 3 predicts poor clinical outcome in gastric adenocarcinoma. APMIS 2009; 117: 598–606. There are no known reliable biomarkers which can predict poor clinical outcome following curative resection of gastric adenocarcinoma. Given the importance of signal transducer and activator of transcription 3 (STAT3) activation in carcinogenesis, we attempted to determine whether STAT3 activation is prognostic of survival in curatively resected gastric cancer patients. We analyzed 311 surgically resected gastric cancer specimens for STAT3 activation and its downstream molecules such as matrix metalloproteinase (MMP)‐9, MMP‐10, cyclin D1, survivin, vascular endothelial growth factor (VEGF)‐C, and VEGFR‐3 using immunohistochemical studies and assessed their correlation with clinical outcome. Using immunohistochemistry, 303 specimens were interpretable for pSTAT3 tyr705 expression. The pSTAT3 was detected in 79 (26.1%) of 303 gastric cancers. Of the downstream molecules tested, STAT3 activation was significantly associated with MMP‐9 and MMP‐10 expressions. On univariate analyses, 5‐year disease‐free survival (DFS) and overall survival (OS) for the tumors with STAT3 activation were considerably poorer than for those without STAT3 activation with statistical significance (5‐year DFS 58.2% vs 68.3%; pSTAT3(−) vs pSTAT3(+); p = 0.0223; 5‐year OS 59.5% vs 70.5%; pSTAT3(−) vs pSTAT3(+); p = 0.0128). On multivariate analyses, STAT3 activation was independently associated with inferior DFS (p = 0.049, hazard ratio [HR] = 1.445, 95% CI, 1.025, 2.120) along with AJCC stage IIIA or IIIB (p = 0.004, HR = 1.708, 95% CI, 1.178, 2.475). The STAT3 activation was also strongly correlated with inferior OS (p = 0.042, HR = 1.506, 95% CI, 1.025, 2.213). Based on our data, pSTAT3 tyr705 may be a novel prognostic marker for poorer clinical outcome following curative resection and adjuvant therapy in gastric cancer. The clinical impact of a STAT3‐targeted agent should be investigated in gastric cancer patients.