Clinicopathological implications of the expression of hypoxia-related proteins in gastric cancer.
OBJECTIVE
Tumor hypoxia confers poor prognosis of a wide range of solid tumors due to increased malignancy, increased likelihood of metastasis and treatment resistance. The aim of this study was to assess the significance of the expression of HIF-1α and HIF-1α-inducible proteins in gastric cancer and their impact on prognosis.


METHODS
The expression of HIF-1α, GLUT-1, CA-9, and iNOS proteins was analyzed by immunohistochemistry in 193 gastric adenocarcinomas (GAs) and 20 normal gastric mucosa.


RESULTS
HIF-1α, GLUT-1, CA-9 and iNOS were expressed in 52.3%, 43.0%, 57.0%, and 43.0% of GAs, respectively, which are higher than the normal counterparts except for CA-9. HIF-1α expression was positively correlated with the expression of GLUT-1, CA-9 and iNOS. GLUT-1 expression was higher in the intestinal type (p = 0.012); however, iNOS expression was higher in the less-differentiated type and the diffuse type (p = 0.006, p = 0.032, respectively). The expression of HIF-1α and GLUT-1 was significantly correlated with lymph node metastasis (p = 0.009, p = 0.008, respectively), while the expression of GLUT-1 and iNOS was significantly correlated with the depth of invasion and advanced stage (p = 0.044, p = 0.004; p = 0.009, p = 0.008, respectively). Overall survival was shorter in patients with GLUT-1 expression than in those without GLUT-1 expression, which was statistically significant by univariate analysis (p = 0.042). On multivariate analysis, however, stage was determined as the only independent prognostic marker (p < 0.001).


CONCLUSIONS
Our data suggest that overexpression of HIF-1α, GLUT-1, and iNOS may play an important role in gastric cancer progression. GLUT-1 is a potential candidate for predicting patient survival.
Department of Hospital Pathology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Republic of Korea.
Ji-Han
JH
Jung
Soyoung
S
Im
Eun Sun
ES
Jung
Chang Suk
CS
Kang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism*; D005260:Female; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*
D000951:Antigens, Neoplasm; D051272:Glucose Transporter Type 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D052247:Nitric Oxide Synthase Type II; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases
CA-9; GLUT-1; Gastric cancer; HIF-1α; hypoxia; iNOS