Immuno-phenotype of mutant ras p21 and early response to radiotherapy in cancer of the uterine cervix

Previous studies have postulated that ras gene mutations may influence cell ular response to radiotherapy. However, clinical studies have often been li mited by the cumbersome methodology associated with DNA analysis. The avail ability of ELISA method has eventually made clinical evaluation of ras gene mutation feasible. In this study ras mutation by in vitro identification o f four mutant forms of p21 ras in cervical tumor tissue extracts was analyz ed. Mutant ras proteins were evaluated by an Enzyme Linked Immunosorbent As say (ELISA). Expression of ras p21 mutations was studied in 101 patients, a nd a correlation between pre-treatment experimental analyses and the clinic al status of the patient after radiotherapy (up to 16 months follow up) was established. There was no correlation between the presence of Val 12 p21 a nd tumor response to radiotherapy. Yet, presence of the other three mutant proteins had significant relationship to treatment outcome. Detection of Ar g 12 mutation was more common in patients who either had residual disease o r developed recurrences (28%) as compared to those remaining disease-free ( 1.5%). The presence of the Arg 12 mutation therefore correlated to poor pro gnosis (r = 0.445, p = 0.0000). Similarly, the Asp 12 mutation was also mor e common in patients with residual/recurrent dis ease (25%) as compared to patients remaining disease-free (3%). Asp 12 mutation also showed a correla tion to treatment outcome (r = 0.337, p = 0.00057). Asp 13 mutation was mor e frequent in patients with residual or recurrent disease (28%) as compared to those remaining disease-free (4.6%). On the basis of laboratory evidenc e ras genes appear to be involved as modulators of tumor response to radiat ion therapy. This understanding of the involvement of specific genes in rad ioresistance will result in the improvement of potential therapies that can be targeted at specific genes, through approaches such as selective inhibi tion by anti-sense oligonucleotides.