Expression of a hypoxia-associated protein, carbonic anhydrase-9, correlates with malignant phenotypes of gastric carcinoma.
OBJECTIVE
Gastric cancers are characterized by a heterogeneously hypoxic environment. Hypoxia might stimulate the malignant potential of cancer cells. The purpose of our study was to clarify the significance of hypoxia in gastric carcinoma by evaluating the expression of a hypoxic marker, namely carbonic anhydrase-9 (CA-9).


METHODS
A total of 265 patients who had undergone a resection of the primary tumor and were confirmed histologically to have sporadic gastric cancer were enrolled in this study. We evaluated the immunohistochemical expression of CA-9 in the paraffin-embedded specimens of 265 gastric adenocarcinomas.


RESULTS
The CA-9 expression was positive in 88 (33%) of 265 gastric carcinomas. The CA-9 expression level was significantly high in cases of type 4 carcinoma (60%, p < 0.001) and diffuse type carcinoma (41%, p < 0.001), and significantly correlated with the invasion depth (p < 0.001), lymph node metastasis (p < 0.001) and lymphatic invasion p = 0.002). The prognosis for CA-9-positive patients was significantly poorer than that of CA-9-negative patients (p = 0.003, log-rank).


CONCLUSIONS
Hypoxia might be associated with aggressive tumor phenotypes of gastric carcinomas. The hypoxic marker CA-9 may be a useful prognostic indicator.
Kato
Yukihiro
Y
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka, Japan.
Yashiro
Masakazu
M
Noda
Satoru
S
Kashiwagi
Shinichiro
S
Matsuoka
Junko
J
Fuyuhiro
Yuhiko
Y
Doi
Yosuke
Y
Hirakawa
Kosei
K
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002256:Carbonic Anhydrases / Q000096:biosynthesis*; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015996:Survival Rate
D014408:Biomarkers, Tumor; D002256:Carbonic Anhydrases