Phosphorylated Akt Expression as a Favorable Prognostic Factor for Patients Undergoing Curative Resection and Adjuvant Chemoradiotherapy for Proximal Extrahepatic Bile Duct Cancer

Objectives: 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) expressions in patients undergoing adjuvant chemoradiotherapy (CRT) for proximal extrahepatic bile duct (EHBD) cancer. Methods: Sixty-three patients with proximal EHBD cancer who underwent curative resection followed by adjuvant CRT 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 to 54 Gy). 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 24 patients (38.1%), respectively. p-Akt expression was associated with distant metastasis and overall survival (OS), but not with locoregional recurrence. The 5-year distant metastasis-free and OS rates were 25.8% versus 58.2% (P=0.007), and 27.5% versus 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), whereas p-Akt expression had a borderline significance (P=0.0541). As for OS, p-Akt expression was a marginally significant prognosticator (P=0.0635), whereas other risk factors lost the statistical significance. Conclusion: p-Akt expression tended to be associated with a favorable prognosis in patients undergoing curative resection followed by adjuvant CRT for proximal EHBD cancer.