Abstract B10: Predictive and prognostic biomarkers at personalized treatment of locally advanced cervical cancer
Authors: Moreno-Acosta Pablo , Gamboa Oscar , Romero-Rojas Alfredo , Acosta Jinneth , Cotes Mestre Martha , Mayorga Diana , Pacheco Magda , Aguilera Gladys , Magné Nicolas 
Published: May 2016

Introduction: Cervical cancer is one of the most prevalent malignancy and of higher mortality in the world, and is considered a marker of underdevelopment. Conventional radiotherapy is one of the treatments used for this type of cancer. 30 to 40% of patients with similar prognosis factors not respond equally to a comparable standard treatment. The poor response to radiotherapy leads to the development of innovative and effective therapies for cervical cancer locally advanced, metastatic and refractory. A comparative analysis of cervical cancer in the context of other cancers may reveal that it is relatively smaller number of targeted molecular agents that have been tested. Accordingly, a number of biological agents are currently in clinical development for the purpose of, inhibiting angiogenesis, molecularly address EGFR and IGF-1R, modulation of cell cycle, of histone deacetylases, COX-2, mTOR and tumor microenvironment (hypoxia and glycolysis). Within work that we have been developing, reported that gene expression of IGF1R is a strong predictive marker for lack of response to radiotherapy, patients have 28.6 times higher risk of failure treatment; Patients & Methods: This prospective cohort study included 149 patients with squamous cell carcinomas of the uterine cervix in FIGO stages IIB and IIIB between 2008 and 2011. The mean age was 46 years. Of the 149 patients, 61 were treated with radiotherapy and 88 with concurrent radiochemotherapy. Expression of the proteins CAIX, GLUT-1, HIF1α, HKII, IGF-IRα, IGF-IRβ and Survivin was determined by immunohistochemistry and P53 Arg72Pro polymorphism by allele specific PCR in biopsies taken before treatment. Results: The highest increase was found in expression of GAPDH (100%), Survivin (87%), followed of, IGF-IRα (76.5%), IGF-IRβ (74.5%), IGF-IRα and IGF-IRβ concordance in the expression(73%), HIF1α (74.1%); strong expression was observed with low frequency for GLUT-1 (31.1%), CAIX (16.2%), HKII (10.6%). For polymorphism Arg72Pro of P53 was found that genotype Arg/Arg is the most frequently (59.8) in patients with cervical locally advanced cancer and that compared to the control group (non-tumor tissue of the cervix with histopathologic diagnosis of cervicitis without evidence of squamous intraepithelial lesion or malignancy) (P = 0.000), and published reports, his presence confirms their possible participation in the development of this cancer, however we found no association with the outcome and response to treatment. Patients who received chemoradiotherapy compared to those who received radiotherapy showed higher survival times, both for overall survival and disease-free. Patients with hemoglobin levels ≤ 11g/dl had a risk 2.53-fold (p = 0.01) decrease in both the overall survival rate as the rate of disease-free survival. Conclusions: We found that the expression of IGF-IRβ detected by immunohistochemistry is a prognostic marker that affects overall survival and disease-free survival; the detection and study before treatment of the expression of HIF1α, CAIX, GLUT 1 and HKII, considered as biological factors pre-existing, contributes to infer the metabolic and hypoxic state, as also at the rational use of new modalities in radiotherapy, radiochemotherapy and gene therapy in the regulation of hypoxia.

Citation Format: Pablo Moreno-Acosta, Oscar Gamboa, Alfredo Romero-Rojas, Jinneth Acosta, Martha Cotes Mestre, Diana Mayorga, Magda Pacheco, Gladys Aguilera, Nicolas Magné. Predictive and prognostic biomarkers at personalized treatment of locally advanced cervical cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B10.