The significance of CD44 expression in gastrointestinal neuroendocrine tumors

Background/Aims: Expression of CD44 and its isoforms has been demonstrated to be a prognostic marker in many neoplasms. Gastrointestinal neuroendocrine tumor is a slow-growing neoplasm, whose behavior is determined by site of occurrence, size or specific histologie growth pattern. In this study, the feasibility of using CD44 as a prognostic marker in gastrointestinal neuroendocrine tumor is evaluated. Methodology: Representative paraffin-embedded sections of gastrointestinal neuroendocrine tumor from 22 patients were studied by immunohistochemical staining using monoclonal antibodies against CD44, Ki-67, and p53 retrospectively. The correlation between these markers and clinical behavior of the tumors was analyzed. Results: Positive expression of CD44 was observed in 15 cases (68%) of gastrointestinal neuroendocrine tumor. Expression of CD44 showed significant inverse correlation with lymph node status (P=0.049), distant metastasis (p<0.001) and mortality (p=0.002). Neither p53 nor Ki-67 correlated with lymph node status, distant metastasis and overall survival. Both lymph node status and distant metastasis showed strong correlation to survival after multivariate analysis. Patients with the tumor growing from the hindgut had better survival (p=0.024). The patients with stronger CD44 immunoreactivity (≥2+) tumors had significantly favorable survival (p = 0.004) compared with those with weaker immunoreactivity (≤+) tumors. Conclusions: Expression of CD44 in gastrointestinal neuroendocrine tumor inversely correlates with tumor metastasis, associates with a favorable outcome and may serve as one of the prognostic indicators.