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


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.
Head and Neck Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Paolo
P
Bossi
Federica
F
Perrone
Rosalba
R
Miceli
Giulio
G
Cantù
Luigi
L
Mariani
Ester
E
Orlandi
Carlo
C
Fallai
Laura D
LD
Locati
Barbara
B
Cortelazzi
Pasquale
P
Quattrone
Paolo
P
Potepan
Lisa
L
Licitra
Silvana
S
Pilotti
D000230:Adenocarcinoma / Q000601:surgery / Q000628:therapy*; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005005:Ethmoid Sinus / Q000473:pathology* / Q000601:surgery; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D060828:Induction Chemotherapy; D002955:Leucovorin / Q000008:administration & dosage; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D010255:Paranasal Sinus Neoplasms / Q000601:surgery / Q000628:therapy*; D011880:Radiotherapy Planning, Computer-Assisted; D018714:Radiotherapy, Adjuvant; D020266:Radiotherapy, Conformal; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D014803:Vitamin B Complex / Q000008:administration & dosage
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D014803:Vitamin B Complex; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil