Abstract
BackgroundOverexpression of Bmi-1 has been observed in a variety of cancers, and it has been suggested to be an independent prognostic marker for the patients. The objective of this study was to determine the level of Bmi-1 expression or its autoantibodies in human esophageal squamous cell carcinoma (ESCC) and to correlate it with clinicopathologic data.MethodsWe first examined Bmi-1 expression in ESCC cell lines and tumor samples by RT-PCR and Western blot analysis. We then analyzed Bmi-1 protein expression in 171 clinicopathologically characterized ESCC cases by immunohistochemistry. In addition, we detected its autoantibodies in sera of patients with ESCC by ELISA.ResultsWe found that Bmi-1 expression was higher in the immortalized cells, cancer cell lines and most cancer tissue than in non-tumorous control tissue at both mRNA and protein level. In addition, Bmi-1 expression was observed in 64.3% (110 of 171) archive ESCC specimen by immunohistochemistry analysis, and the location of Bmi-1 in ESCC was in the nuclei instead of cytoplasm of tumor cells. There was a significant difference of Bmi-1 expression in patients categorized according to stage (P = 0.003) and pN classification (P = 0.047). Multivariate analysis suggested that Bmi-1 expression was an independent prognostic marker for ESCC patients. A prognostic significance of Bmi-1 was also found in the subgroup of T3~T4 and N1 tumor classification. Bmi-1 autoantibodies were detected in sera of 39.0% (62 of 159) ESCC patients. The correlations between anti-Bmi-1 antibodies and tumor stage (P = 0.040), or lymph node status (P < 0.001) were significant.ConclusionsOur results suggest that Bmi-1 protein is a valuable marker of ESCC progression. The presence of Bmi-1 autoantibodies in sera from patients with ESCC may have clinical utility in esophageal cancer diagnosis.
Highlights
Overexpression of Bmi-1 has been observed in a variety of cancers, and it has been suggested to be an independent prognostic marker for the patients
We have reported that overexpression of Bmi-1 leads to the induction of telomerase activity, reduction of p16INK4a expression, and immortalization of normal nasopharygeal epithelial cells (NPECs)[16]
He et al.[25] reported that Bmi-1 was overexpressed in esophageal squamous cell carcinomas, and Bmi-1 mRNA expression correlated with lymph node metastases, pathological stage and poor prognosis of the patients
Summary
Overexpression of Bmi-1 has been observed in a variety of cancers, and it has been suggested to be an independent prognostic marker for the patients. It has been found that Bmi-1 is overexpressed in a variety of human cancers, such as mantle cell lymphomas[18], non-small cell lung cancer[19], B-cell non-Hodgkin’s lymphoma[20], breast cancer[21], colorectal cancer[22], prostate cancer[23], nasopharyngeal carcinoma[16] and gastric carcinoma[24] In these reports, Bmi-1 protein mainly locates in nuclei of tumor cells. Bmi-1 protein mainly locates in nuclei of tumor cells He et al.[25] reported that Bmi-1 was overexpressed in esophageal squamous cell carcinomas, and Bmi-1 mRNA expression correlated with lymph node metastases, pathological stage and poor prognosis of the patients. It is required further investigation to determine whether the cytoplasm staining represents the real localization of Bmi-1, and whether Bmi-1 plays a different role in the development of ESCC
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