Tp53 status as guide for the management of ethmoid sinus intestinal-type adenocarcinoma

Oral Oncol. 2013 May;49(5):413-9. doi: 10.1016/j.oraloncology.2012.12.011. Epub 2013 Jan 29.

Abstract

Objective: Intestinal-type adenocarcinoma (ITAC) of the ethmoid sinus is a rare, occupational-related tumor. Optimal treatment consists of surgery and radiotherapy, while chemotherapy is still investigational. The molecular profile of ITAC is characterized by the occurrence of TP53 mutations associated with genotoxic agents such as wood dust. We investigated the role of p53 functionality in relation to the primary treatment.

Materials and methods: We retrospectively reviewed 100 medical charts of consecutive patients with a first diagnosis of ITAC treated at our Institute; 74 patients were evaluable for TP53 analysis. Thirty (41%) were treated from 1991 to 2006 with craniofacial resection followed by radiotherapy (Group A), compared with 44 patients (59%) treated from 1996 to 2006 with cisplatin-based induction chemotherapy (PFL) followed by standard treatment (Group B).

Results: Five-year OS in Group A was 42%, while in Group B it was 70% (p = 0.041); 5-year DFS in Group A was 40%, while in Group B it was 66%, (p = 0.009) (p = 0.061 and 0.003 at Cox multivariable OS and DFS analyses). Analyzing each group according to p53 functional status, only for Group B patients (who received preoperative chemotherapy) both OS and DFS were in favor of functional p53 (p = 0.023 and p = 0.010, respectively). No impact of p53 functional status as a biomarker was observed in Group A.

Conclusions: Functional p53 may predict PFL-chemotherapy efficacy, offering a possible increase in survival when induction chemotherapy is given to a selected population. On the other hand, upcoming innovative approaches should be explored in the presence of non-functional p53.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / surgery
  • Adenocarcinoma / therapy*
  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / analysis*
  • Cisplatin / administration & dosage
  • Cisplatin / therapeutic use
  • Disease-Free Survival
  • Dose Fractionation, Radiation
  • Ethmoid Sinus / pathology*
  • Ethmoid Sinus / surgery
  • Fluorouracil / administration & dosage
  • Follow-Up Studies
  • Genes, p53 / genetics
  • Humans
  • Induction Chemotherapy
  • Leucovorin / administration & dosage
  • Middle Aged
  • Mutation, Missense / genetics
  • Neoadjuvant Therapy
  • Neoplasm Staging
  • Paranasal Sinus Neoplasms / surgery
  • Paranasal Sinus Neoplasms / therapy*
  • Radiotherapy Planning, Computer-Assisted
  • Radiotherapy, Adjuvant
  • Radiotherapy, Conformal
  • Retrospective Studies
  • Survival Rate
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / analysis*
  • Vitamin B Complex / administration & dosage

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Vitamin B Complex
  • Cisplatin
  • Leucovorin
  • Fluorouracil