Expression of CD133 in the cytoplasm is associated with cancer progression and poor prognosis in gastric cancer

BACKGROUND: CD133 is one of the most important stem cell markers in solid cancers. Some recent reports have described a possible relationship between CD133 and hypoxia-inducing factor-1-alpha (HIF-1α). The aim of this study was to clarify the clinical role of CD133 expression in gastric cancer and to investigate the correlation between CD133 expression and HIF-1α expression. METHODS: We studied 189 gastric cancer patients who underwent gastrectomy at Kurume University Hospital. CD133 and HIF-1α expression was examined using immunohistochemical staining. Fifty-six cases were CD133 positive, and they were divided into two expression types: luminal expression of the gland and cytoplasmic expression. We investigated the relationship among CD133 expression types, clinicopathological variables, prognosis, and HIF-1α expression. RESULTS: When comparing clinicopathological variables, expression of CD133 in the cytoplasm was related to metastasis and tumor progression. However, this relationship was not observed with luminal expression of the gland type. The survival rate in patients with cytoplasmic CD133 expression was significantly worse than that in the CD133-negative group. This relationship was observed in the survival rate of the adjuvant chemotherapy group and the curative resection group. Multivariate analysis revealed that the expression of CD133 in the cytoplasm was an independent prognostic factor in gastric cancer. Regarding the correlation between CD133 expression and HIF-1α expression, the HIF-1α positive rate was lower in patients with CD133 luminal expression of the gland type and higher in patients with cytoplasmic expression of CD133. CONCLUSION: Gastric cancer cells with CD133 expression in the cytoplasm were cells with high potential for malignancy, and this phenotype was associated with cancer progression, chemotherapy resistance, recurrence, and poor prognosis. Cytoplasmic expression of CD133 may be a useful prognostic marker in gastric cancer. Significant correlation was observed between HIF-1α expression and the immunohistochemical staining pattern of CD133.