Abstract B61: Ha-RAS mutations in fibroblast of the cervical stroma of squamous neoplasias of the uterine cervix

Abstract

Abstract The stroma is maintained, renovated, and repaired by resident fibroblasts, supports and instructs the epithelium, and is essential for epithelial function. Now recognized that stromal changes are necessary for the establishment of cancer and previously considered as a spectator in front of the clonal expansion and acquisition of malignant characteristics of tumor cells. Most studies on the stroma and t its relationship with the generation, progression and metastasis of cancer in which involve multiple steps of tumorigenesis and the microenvironment, have focused especially on cancers such as breast and others as cancer of prostate, gastric, colorectal and cervical cancer. Reports of cervical cancer specifically address issues such as clonality and genomic features in cervical carcinogenesis. However, the presence of mutations Ha-RAS oncogen in stromal cells and their contribution to the generation and progression of cervical squamous neoplasia has not yet been reported. The aim of this study was detect and determine the frequency of mutations Ha-RAS in stromal fibroblasts from biopsies of the transformation zone of the uterine cervix. We selected eight samples of fresh frozen tissue of patients diagnosed with cervical intraepithelial neoplasia squamous (CIN I, CIN II, CIN III), cancer in situ and invasive squamous cell carcinoma, tissue in which it was represented only the stroma, without evidence of residual tumoral epithelial component, and each of whom had cervical tissue in paraffin-embedded control confirming the presence of cervical squamous neoplasia. The detection of Ha-ras mutations in codon 12 was performed using a nonradioactive PCR-SSCP and restriction enzyme analysis. The mutation found for a substitution of a glycine by a valine at codon 12 of Ha-RAS was detected in alone sample (12.5%), CIN III. The non-detection of the GTC mutation in the remaining seven samples could be due to somatic mutation that this represented only a small fraction (approximately 15%) of total DNA analyzed (33), as well as a topographical heterogeneity likely distribution of these mutations. The presence of a point mutation of Ha-RAS oncogene in the stroma of one case studied, represents an important change, this mutation prevents the conversion of active to inactive form, and suggest an alternative pathway involving stromal genetic instability in the generation of intraepithelial neoplasia and progression of the cervical cancer. Citation Information: Cancer Prev Res 2010;3(1 Suppl):B61.