p53 Tumor Suppressor Protein and H-RAS Oncogene in Maxillofacial Tumors: Immunohistochemical and Genetic Investigation, Induction Chemotherapy Response and Prognosis Evaluation

Abstract

The authors carried out immunohistochemical and genetic research on the tumor suppressor protein p53 and H-RAS oncogene in oromaxillofacial neoplasms. The purpose was to verify, genetically, the presence of correlations between the degree of histopathological overexpression (per cent) of oncogenes and chemoresistance. The study was carried out on 15 patients with squamous cell carcinoma of the oromaxillofacial region, of equal histopathological grade (G2), who underwent neoadjuvant chemotherapy: cis-diaminodichloroplatinum (CDDP, 20 mg/m² i.v. days 1-5) and 5-fluorouracil (5-FU 1000 mg/m² continuous infusion, volumetric pump 2 ml/h, for 5 days). Restaging was carried out after three cycles of chemotherapy to evaluate clinical response. The p53 immunohistochemical study (clone DO-7) showed a pathological overexpression in 9/15 cases; whereas the genetic exam (PCR method, wild DNA) showed mutations in 5/15 cases, with individual corresponding percentages of 95%, 80%, 70%, 45% and 95%. The H-RAS immunohistochemical study (AB-1) (clone 235-1.7.1) showed a pathological overexpression in 12/15 cases; the genetic exam showed mutations in 9/15 cases, corresponding to, respectively, 90%, 35%, 10%, 20%, 77%, 90%, 85%, 25%, 75%. The response to the neoadjuvant chemotherapy was as follows: 2 partial responses (PR) (90%) in 1 tumor of the cheek and in 1 tumor of the soft palate, with global survival (GS) of, respectively, 18 and 15 months. 1 PR (75%) and 4 PR (55%) in 5 tumors of the gum, with GS of, respectively, 10, 6, 8, 9 and 8 months. Two objective improvements (OI) in, respectively, 1 tumor of the floor of the mouth and 1 tumor of the gum, with GS of, respectively, 5 and 6 months. Three patients had stable disease (S) in 2 tumors of the tongue and 1 tumor of the gum, with GS of, respectively, 10, 7 and 7 months. Three patients had progression (P) in 2 tumors of the floor of the mouth and in 1 tumor of the cheek, with GS of, respectively, 8, 8 and 6 months.

This study showed some correlation between genetic analysis and immuno-histochemical investigation of 73.3% of cases for p53 and of 80% of cases for H-RAS (Chi-Square Test: p=0.3089). These data do not permit definition of the range of onocogene overexpression which corresponds to mutation, thus serving as a marker of chemoresistance. However, the cases studied confirm that, in regard to p53, there is a certain degree of correlation between absence of mutations and sensitivity to neoadjuvant chemotherapy.