J Gynecol Oncol.  2010 Sep;21(3):181-185. 10.3802/jgo.2010.21.3.181.

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

• Kim MK
• Kim TJ
• Sung CO
• Choi CH
• Lee JW
• Kim BG
• Bae DS

• KMID: 1980855
• DOI: http://doi.org/10.3802/jgo.2010.21.3.181

Abstract

OBJECTIVE
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.

Keyword

Cervical neoplasms; Radiation; mTOR; Resistance

MeSH Terms

Biopsy
Case-Control Studies
Cell Proliferation
Cytoplasm
Disease-Free Survival
Humans
Immunohistochemistry
Recurrence
Sirolimus
Uterine Cervical Neoplasms
Sirolimus

Figure

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  Fig. 1 Proportion score (PS) and intensity score (IS) of mammalian target of rapamycin (mTOR) expression. A, 0% (0); B, 5% (1); C, 80% (2); D, 85% (3).

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  Fig. 2 Univariate progression-free survival (PFS) analysis of phosphorylated- mammalian target of rapamycin (p-mTOR) expression in 36 patients with locally advanced cervical cancer; mTOR strong staining group (intensity score [IS]=2,3) had a poorer prognosis for progression free survival (PFS) (p=0.02).

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