Dual role of CD44 isoforms in ampullary adenocarcinoma: CD44s predicts poor prognosis in early cancer and CD44ν is an indicator for recurrence in advanced cancer
BACKGROUND Transmembrane proteins of the CD44 family play roles in cell-cell and cell-matrix interactions, and their aberrant expression has been reported to be associated with the growth and metastasis of various tumors. The authors examined CD44 standard (CD44st) and CD44 variant 6 (CD44v6) expression in extrahepatic bile duct (EHBD)/ampullary carcinoma. METHODS In 36 EHBD/ampullary carcinomas, immunohistochemical analyses with monoclonal antibodies against the human CD44st protein or CD44v6 protein were performed by the streptavidin-biotin immunoperoxidase method. The relation between expression of the proteins and lymph node metastases or patient outcome was investigated. To verify the lack of CD44v6 mRNA expression in tumors negative for CD44v6 staining, reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot hybridization were performed. RESULTS Immunohistochemical analyses revealed that 13 of 36 carcinomas (36.1%) expressed the CD44v6 protein. Only 2 of 13 CD44v6-expressing primary tumors (15.4%) had regional lymph node metastases, whereas 14 of 23 tumors showing no CD44v6 expression (60.9%) had lymph node metastases (Fisher exact test, P<0.01). Moreover, a lack of CD44v6 expression was correlated significantly with poor prognosis (generalized Wilcoxon test, P<0.05). Eleven of 13 CD44v6 positive tumors showed CD44st expression, which also was correlated with prognosis. RT-PCR and Southern blot hybridization revealed a lack of CD44v6 mRNA expression in the tumors that were negative for CD44v6 staining. CONCLUSIONS The results of the current study suggest that a lack of expression of CD44, especially CD44v6, is correlated with lymph node metastases and poor prognosis, and may be a prognostic factor for patients with EHBD/ampullary carcinoma.