The major causes of treatment failure in cancer are the development of metastases and drug resistance. Recently, hyaluronan (HA)-induced interaction between CD44, a HA receptor, has been shown to promote ankyrin, a cytoskeltol protein, binding to multidrug transporter MDR1 (p-glycoprotein) resulting in therapy resistance. However, their clinical significance isn\#8217;t elucidated yet in esophageal cancer progression. Here, we analyzed whether CD44 expression could predict disease recurrence and prognosis in esophageal cancer patients undergoing neoadjuvant chemoradiotherapy (CRT). Among 79 patients with histologically confirmed esophageal squamous cell carcinomas (ESCCs), 38 showed CD44 positive expression (48.1%). Overall survival (OS) was significantly associated with lymph-node metastasis, distant metastasis and CRT, and was further correlated with the absence of both CD44 expression and residual tumor. Furthermore, patients with CD44-positive cancers showed significantly poorer prognoses than those without (Disease-Free Survival; mean DFS time 22.1 vs 73.7 months, 3-yr DFS 20.2% vs 51.6%, P<0.005, OS; mean OS time 26.3 vs 77.6 months, 3-yr OS 18.9% vs 52.0%, P<0.01). Our study has shown that CD44 expression is a strong and independent predictor of early relapse and poor prognosis in ESCC after CRT. These findings suggest that CD44 is a link between relapse and CRT-resistant cancer cells, and is thus a potential prognostic biomarker and rationale therapeutic target for \#8216;more aggressive\#8217; cancer cells leading to recurrence.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1634.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO