title: Predictive and prognostic role of activated mammalian target of rapamycin in cervical cancer treated with cisplatin-based neoadjuvant chemotherapy.
abstract: The present study was designed to clarify the expression and prognostic significance of activated Akt and mTOR in cervical cancer and their correlation with response to neoadjuvant chemotherapy (NAC). Immunohistochemical analysis for p-Akt and p-mTOR expression was performed on paraffin-embedded biopsy specimens from 25 patients with advanced cervical cancer (stage Ib2-IIb). We correlated this finding with various clinicopathological variables and prognosis by uni- and multivariate analyses. All patients received cisplatin-based NAC, and primary tumor response was evaluated by RECIST criteria and then classified as a positive or negative response. Activation of Akt was detected in the cytoplasm and nucleus of the cancer cells in 12 patients (48%), whereas p-mTOR was detected in the cytoplasm and membrane of the cancer cells in 13 patients (52%). Post NAC evaluation of the primary tumor revealed 68% (17/25) responsive tumors. The expression of p-mTOR and distant metastasis significantly correlated with the response to NAC (p = 0.0101 and p = 0.0107); however, there was no significant correlation between p-Akt and p-mTOR expression and any of the clinicopathological characteristics of the patients. In the univariate analysis, activated Akt and mTOR were found to be significant prognostic indicators (p < 0.05). In multivariate analysis, p-mTOR expression retained its significance as an independent poor prognostic marker (p = 0.0178). In summary, our present study showed that cervical cancer expressed Akt and mTOR activation. Moreover, the expression of phosphorylated mTOR may have a role as a marker to predict response to chemotherapy and survival of cervical cancer patients who are treated with cisplatin-based neoadjuvant chemotherapy. Our results suggest that the mTOR cascade may be a promising target for therapeutic intervention in cervical cancer.
authors.affiliation: Department of Gynecology and Reproductive Medicine, Graduate School of Medicine, Gunma University, Maebashi, Gunma 371-8511, Japan. leri@med.gunma-u.ac.jp
authors.forename: Leri S
authors.initials: LS
authors.lastname: Faried
authors.forename: Ahmad
authors.initials: A
authors.lastname: Faried
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kanuma
authors.forename: Takaaki
authors.initials: T
authors.lastname: Sano
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nakazato
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Tamura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuwano
authors.forename: Takashi
authors.initials: T
authors.lastname: Minegishi
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000494:pharmacology*; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D011379:Prognosis; D011494:Protein Kinases / Q000096:biosynthesis*; D058570:TOR Serine-Threonine Kinases; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D002945:Cisplatin