182 Background: To evaluate the prognostic significance of phosphorylated Akt (p-Akt), phosphorylated mammalian target of rapamycin (p-mTOR), and total phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression in patients undergoing adjuvant chemoradiotherapy for proximal extrahepatic bile duct (EHBD) cancer. Methods: Sixty-three patients with proximal EHBD cancer who underwent curative resection followed by adjuvant chemoradiotherapy were enrolled into this study. Postoperative radiotherapy was delivered to tumor bed and regional lymph nodes up to a median of 40 Gy (range; 40-54). Fifty-nine patients also received fluoropyrimidine chemotherapy as a radiosensitizer. p-Akt, p-mTOR, and PTEN expression were assessed with immunohistochemical staining on the tissue microarray. Results: p-Akt, p-mTOR, and PTEN were expressed in 23 (36.5%), 17 (27.0%) and 25 patients (39.7%), respectively. p-Akt expression was associated with distant metastasis and overall survival, but not with loco-regional recurrence. The 5-yr distant metastasis-free and overall survival rates were 25.8% vs. 58.2% (p = 0.007), and 27.5% vs. 50.2% (p = 0.0167) in patients with negative and positive expression, respectively. On multivariate analysis, nodal involvement was the only significant prognosticator predicting inferior distant metastasis-free survival (p = 0.0105), while p-Akt expression had a borderline significance (p = 0.0541). As for overall survival, p-Akt expression was a marginally significant prognosticator (p= 0.0635), whereas other risk factors lost the statistical significance. Conclusions: p-Akt expression was a favorable prognostic factor for patients undergoing curative resection followed by adjuvant chemoradiotherapy for proximal EHBD cancer.
Cytoplasmic CD133 expression correlates with histologic differentiation and is a significant prognostic factor in extrahepatic bile duct cancer and gallbladder cancer