High expression of mTOR is associated with radiation resistance in cervical cancer

Abstract

Mammalian target of rapamycin (mTOR) is known to promote cell proliferation, survival, and resistance to radiation. The aim of this study was to determine whether mTOR expression was associated with survival and the response to radiation in patients with cervical cancer. After reviewing 119 patients treated by primary radiotherapy for stage IIB-IVA cervical cancer, a case-control study was performed. The cases (n=12) with local recurrence or radiation failure after primary radiation therapy were selected. For each case, two controls that had no recurrence were selected. Using pretreatment paraffin-embedded tissues, the cytoplasmic expression of phosphorylated-mTOR (p-mTOR) was evaluated by immunohistochemistry. Staining was scored based on intensity (intensity score [IS] 0-3) and proportion (proportion score [PS] 0-100). The progression free survival (PFS) was defined from the end of treatment to the day of recurrence by imaging studies or biopsy. The staining distribution and PFS were compared between the two groups. The results were analyzed by the Student t-test, Mann-Whitney U-test, Fisher's exact test, and Cox proportional hazards regression model. The p-mTOR cytoplasmic expression was significantly associated with a poor response to radiotherapy (p<0.01). With respect to survival, a higher cytoplasmic expression of p-mTOR was associated with a worse outcome (p=0.02). The hazard ratio for recurrence or radiation failure was 6.18 for mTOR IS and 1.04 for mTOR PS (p<0.05 for both), indicating that the degree of p-mTOR staining correlated with the recurrence risk. High expression of p-mTOR was associated with radiation resistance; therefore p-mTOR may be a prognostic marker for response to radiotherapy in patients with cervical cancer.