Modulatory Effects of Chemoradiation on Angiogenic Factors and Laminin in Cervical Cancer: Link with Treatment Response

Objective: Carcinoma of the uterine cervix is either the first or second most common malignancy in Indian women, depending on the registry. Tumor growth and metastasis primarily are determined by angiogenesis and parameters of the molecular environment including extracellular matrix elements, growth factors and cytokines. Effects of chemo-irradiation on biomarkers like vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2) and laminin in patients with carcinoma cervix therefore need to be explored. Methods: Circulatory and mRNA levels of VEGF, Ang-2 and laminin in patients with stage III carcinoma cervix (n=40) were compared with those of normal healthy women (n=20). Measurement was prior to treatment, and after chemotherapy and teleradiation, using high sensitivity ELISA kits and Q-PCR. Clinical response was evaluated as per WHO criteria and was assessed for correlation with the biochemical markers. Results: Levels of all the studied molecules were significantly (p<0.001) higher in patients than in controls. After treatment significant decline (p<0.001) was noted. Out of 40 patients, 33 were complete responders and 7 were non-responders on clinical assessment. On comparison of before and after treatment levels of these molecules complete responders showed significant decline whereas non-responders showed non-significant decrease. Follow-up of the responders for 3 years, revealed 28 of 33 patients to still be disease free, the other 5 demonstrating recurrence. Conclusions: Higher levels of angiogenic factors along with laminin indicate roles played in disease progression aiding angiogenesis. These markers may serve as useful tools in post treatment disease mapping, for which available imaging methods may not provide a true picture.