Immunophenotype 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 cellular response to radiotherapy. However, clinical studies have often been limited by the cumbersome methodology associated with DNA analysis. The availability of ELISA method has eventually made clinical evaluation of ras gene mutation feasible. In this study ras mutation by in vitro identification of four mutant forms of p21 ras in cervical tumor tissue extracts was analyzed. Mutant ras proteins were evaluated by an Enzyme Linked Immunosorbent Assay (ELISA). Expression of ras p21 mutations was studied in 101 patients, and a correlation between pre-treatment experimental analyses and the clinical 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 and tumor response to radiotherapy. Yet, presence of the other three mutant proteins had significant relationship to treatment outcome. Detection of Arg 12 mutation was more common in patients who either had residual disease or developed recurrences (28%) as compared to those remaining disease-free (1.5%). The presence of the Arg 12 mutation therefore correlated to poor prognosis (r = 0.445, p = 0.0000). Similarly, the Asp 12 mutation was also more common in patients with residual/recurrent disease (25%) as compared to patients remaining disease-free (3%). Asp 12 mutation also showed a correlation to treatment outcome (r = 0.337, p = 0.00057). Asp 13 mutation was more frequent in patients with residual or recurrent disease (28%) as compared to those remaining disease-free (4.6%). On the basis of laboratory evidence ras genes appear to be involved as modulators of tumor response to radiation therapy. This understanding of the involvement of specific genes in radioresistance will result in the improvement of potential therapies that can be targeted at specific genes, through approaches such as selective inhibition by anti-sense oligonucleotides.
Sreelekha
T T
TT
Division of Laboratory Medicine, Regional Cancer Centre, Thiruvananthapuram, India.
Nair
M K
MK
Jayaprakash
P G
PG
Pillai
M R
MR
D019943:Amino Acid Substitution; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000235:genetics* / Q000401:mortality / Q000532:radiotherapy; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D011905:Genes, ras; D006801:Humans; D016130:Immunophenotyping; D009364:Neoplasm Recurrence, Local; D018365:Neoplasm, Residual; D017354:Point Mutation; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics* / Q000276:immunology; D011836:Radiation Tolerance / Q000235:genetics; D011859:Radiography; D011867:Radioisotope Teletherapy; D013997:Time Factors; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy
D003062:Codon; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)