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

Kim, Byoung Hyuck MD; Kim, Kyubo MD; Min, Hye Sook MD; Chie, Eui Kyu MD; Jang, Jin-Young MD; Kim, Sun Whe MD; Han, Sae-Won MD; Oh, Do-Youn MD; Im, Seock-Ah MD; Kim, Tae-You MD; Bang, Yung-Jue MD; Jang, Ja-June MD; Ha, Sung W. MD

American Journal of Clinical Oncology: April 2017 - Volume 40 - Issue 2 - p 158–162
doi: 10.1097/COC.0000000000000121
Original Articles: Gastrointestinal

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.

Departments of *Radiation Oncology

Pathology

Surgery

Internal Medicine, Seoul National University College of Medicine, Jongno-gu

§Institute of Radiation Medicine, Medical Research Center, Seoul National University, Jongno-gu

Department of Radiation Oncology, Ewha Womans University School of Medicine, Yangcheon-gu, Seoul, Republic of Korea

Supported by Seoul National University Hospital Research Fund, No. 04-2011-0550.

The authors declare no conflicts of interest.

Reprints: Kyubo Kim, MD, Department of Radiation Oncology, Ewha Womans University School of Medicine, Republic of Korea. 1071 Anyangcheon-ro, Yangcheon-gu, Seoul 158-710, Republic of Korea. E-mail: kyubokim.ro@gmail.com.

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