Prognostic value of p53 mutations, bax, and spontaneous apoptosis in maxillary sinus squamous cell carcinoma.
BACKGROUND
Many researchers have attempted to correlate p53 mutation and spontaneous apoptosis with the effectiveness of radiochemotherapy and with prognosis in several malignancies.


METHODS
The current study group consisted of 70 Japanese patients with maxillary sinus squamous cell carcinoma (SCC). Fifty seven patients were treated with radiochemotherapy followed by total or partial maxillectomy, and the remaining 13 patients were treated with radiotherapy alone. Tumor biopsy specimens at pretreatment status were examined for apoptosis-related proteins such as p53 protein, Fas, bax, bcl-x, and apoptosis using immunohistologic methods. The proportion of apoptotic cells labeled by single stranded DNA antibody was expressed as an apoptotic index (AI). p53 mutations at exons 5 through 8 were analyzed by direct sequence on polymerase chain reaction amplified products obtained from laser microdissected tissues. The effectiveness of radiochemotherapy was investigated histologically on surgically dissected specimens.


RESULTS
p53 mutations were identified in 20 (29%) of 70 patients. p53 protein was overexpressed in 39 patients (56%), Fas in 20 patients (29%), bax in 40 patients (57%), and bcl-x in 33 patients (47%). Overexpression of bax was associated with negativity of bcl-x (P = 0.015) and with high AI (P = 0.024). Low AI and/or p53 mutation in the pretreatment tissues correlated with low histologic effectiveness of radiochemotherapy (P = 0.048, P = 0.019, respectively). Kaplan-Meier analysis as well as univariate analysis using the Cox proportional hazards model showed that low histologic effectiveness of radiochemotherapy (P = 0.0281, P = 0.0284, respectively), p53 mutations (P = 0.0095, P = 0.0187, respectively), negativity of bax (P = 0.0069, P = 0.0191, respectively), and low AI (P = 0.0134, P = 0.0407, respectively) were significantly related to worse disease-free survival. Multivariate analysis showed AI as an independent factor predicting for disease-free survival (P = 0.0455).


CONCLUSIONS
The p53 mutations, expression of bax, and levels of spontaneous apoptosis have prognostic value in maxillary sinus SCC; AI especially is an independent factor for disease-free survival. A high level of spontaneous apoptosis induced by overexpression of bax may increase sensitivity of radiochemotherapy resulting in good prognosis, while p53 mutation may lead to resistance against radiochemotherapy, resulting in poor prognosis.
Bandoh
Nobuyuki
N
Department of Otolaryngology, Asahikawa Medical College, Midorigaoka E 2-1-1-1, Asahikawa, Hokkaido 078-8510, Japan.
Hayashi
Tatsuya
T
Kishibe
Kan
K
Takahara
Miki
M
Imada
Masanobu
M
Nonaka
Satoshi
S
Harabuchi
Yasuaki
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008444:Maxillary Sinus Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D018714:Radiotherapy, Adjuvant; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019014:fas Receptor / Q000378:metabolism
C494826:BAX protein, human; C494811:BCL2L1 protein, human; D017931:DNA Primers; D004273:DNA, Neoplasm; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019014:fas Receptor