title: Expression of p53 and apoptosis of tumor cells in locally advanced cervical carcinoma after cisplatin based neoadjuvant chemotherapy.
abstract: Various chemoantiblastic agents cause DNA damage followed by apoptotic cell death through the activation of the p53 suppressor gene. The aim of our study was to evaluate the relationship between p53 protein expression, apoptosis of autologous tumor cells, and clinical response to neoadjuvant chemotherapy in patients with cervical carcinoma. Our study included 14 women with stage II squamous cervical carcinoma who had been admitted to the Institute of Gynecology and Obstetrics, Ancona University, between January 1990 and December 1995. The patients received neoadjuvant combination chemotherapy, consisting of three cycles of cisplatin (80 mg/m2) and bleomycin (30 mg/m2). After chemotherapy, radical surgery was performed. Bioptic specimens were obtained from cervical tumors before and after chemotherapy, and processed for DNA staining and apoptosis, and immunohistochemical staining with a monoclonal antibody against p53. Ten patients (71.4%) showed a clinical response (2 complete, and 8 partial), while of the remaining 4 cases (28.6%) 3 had no change and 1 showed progression after neoadjuvant combination chemotherapy. A significant relationship was observed between the overexpression of p53 and sensitivity to chemotherapy; responder patients showed a higher frequency of p53 positive cells than non-responders (p = .05). A significant direct relationship was observed between p53 protein immunostaining and apoptosis of tumor cells both before (p = .02) and after (p = .01) chemotherapy. Our study seems to define the relationship between p53 expression and sensitivity to cisplatin based chemotherapy in locally advanced cervical carcinoma, supporting the notion that the cytotoxic action of cisplatin can activate p53 mediated apoptosis. However, the limited number of patients in our series does not permit judgement on the clinical implications of the expression of p53 in patients undergoing neoadjuvant combination chemotherapy for locally advanced cervical carcinoma.
authors.affiliation: Institute of Obstetrics and Gynecology, Università degli Studi di Ancona, Italy.
authors.forename: G G
authors.initials: GG
authors.lastname: Garzetti
authors.forename: A
authors.initials: A
authors.lastname: Ciavattini
authors.forename: M
authors.initials: M
authors.lastname: Provinciali
authors.forename: G
authors.initials: G
authors.lastname: Di Stefano
authors.forename: G
authors.initials: G
authors.lastname: Lucarini
authors.forename: G
authors.initials: G
authors.lastname: Goteri
authors.forename: G
authors.initials: G
authors.lastname: Biagini
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D001761:Bleomycin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000601:surgery
chemical_list: D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D001761:Bleomycin; D002945:Cisplatin