p53 expression in locally advanced pharyngeal squamous cell carcinoma.
BACKGROUND
Prognosis for advanced head and neck squamous cell carcinoma remains poor despite advances in treatment, although a small number of patients may benefit from induction therapy leading to increased local control. Mutations of the p53 gene, which are present in a considerable percentage of head and neck squamous cell carcinomas, have been associated with poor response to chemotherapy. The role of p53 protein overexpression (which is associated with p53 gene mutations) in predicting the response to chemotherapeutic agents and survival rates is not clear.


OBJECTIVE
To determine the association of p53 expression with chemotherapy response rates and disease-free survival rates in 62 patients with locally advanced pharyngeal cancer treated with induction cisplatin-5-fluorouracil chemotherapy between 1983 and 1995.


METHODS
Historical cohort. Archival tissue from biopsies done before chemotherapy was immunohistochemically stained for the p53 tumor suppressor gene (clone D0-7; DAKO Corp, Glostrup, Denmark).


RESULTS
Positive staining for p53 occurred in 45 (73%) of 62 cases, with the percentage of reactive cells ranging from 35% to 98%. Chemotherapy response rates were higher in the p53-negative group (15/17 [88%]) compared with the p53-positive group (27/45 [60%]) (P =.07). The risk of recurrence was lower in the p53-negative group compared with the p53-positive group at 2, 3, and 5 years after treatment (P = .03, P = .01, and P = .007, respectively). The median relapse-free survival rates of patients in the p53-negative group was 16 months, whereas those with p53 protein expression demonstrated a median relapse-free survival time of 9 months (P = .07). In multivariate analyses, the only independent factor of relapse-free survival rates was age older than 70 years.


CONCLUSIONS
The present study shows a trend favoring p53 overexpression as a predictive and prognostic factor in locally advanced pharyngeal cancer treated with induction chemotherapy.
Lassaletta
L
L
Department of Otolaryngology, LaPaz University Hospital, Madrid, Spain.
Brandáriz
J A
JA
Benito
A
A
de la Cruz
J
J
Gómez
C
C
Ballestín
C
C
Hitt
R
R
Colomer
R
R
Alvarez-Vicent
J J
JJ
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D010610:Pharyngeal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D011336:Probability; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D016159:Tumor Suppressor Protein p53; D002945:Cisplatin; D005472:Fluorouracil