P53 overexpression in head and neck carcinoma and radiotherapy results.
OBJECTIVE
P53 gene mutations are the common genetic changes encountered in human cancers, and there is extensive evidence that the P53 status may determine tumor response to therapy. This study was carried out to investigate whether there is any correlation between accumulation (overexpression) of P53 protein and poor prognosis in patients with head and neck carcinomas treated with radical radiotherapy.


METHODS
Seventy-nine patients with head and neck carcinomas who were diagnosed and treated in 1989-90 with curative radiotherapy were studied retrospectively. Paraffin sections from archival material were studied using immunohistochemical staining (IHC) with mouse monoclonal antibodies (D0-7) to human P53 protein. Univariate and multivariate analysis of loco-regional tumor control and patient survival were performed on possible prognostic factors.


RESULTS
Forty-two (53%) patients showed positive IHC staining in their tumors. Fifty-three percent of the laryngeal, 64% of the oropharyngeal, and 43% of the oral cavity carcinomas showed P53 overexpression. All tumor specimens with vascular, lymphatic, and/or sarcolemmal invasion showed P53 overexpression. The proportion of tumor-stained nuclei was higher in the poorly differentiated than in the well and moderately differentiated tumors (p < 0.05), but there was no correlation with the patient overall or disease-free 5-year actuarial survival. There was no difference in the 5-year actuarial survival and disease-free survival between patients with P53 immunostaining in their tumors and those with no immunostaining (59% vs. 65% and 57% vs. 51%, respectively). The TNM tumor stage was the most significant prognostic factor with 5-year actuarial survival of 87% for early and 14% for late stages (p << 0.0001). There was a significant correlation between immunostaining and history of smoking (p = 0.02).


CONCLUSIONS
The data demonstrate that the P53 accumulation as detected by immunohistochemical staining in a group of head and neck carcinomas was not predictive of patient's poor survival or disease-free survival. Multivariate statistical analysis showed that the TNM tumor stage was the only significant prognostic factor. There was a significant association between P53 accumulation and smoking.
Awwad
S
S
Northern Center for Cancer Treatment, Newcastle General Hospital, Newcastle Upon Tyne, UK.
Jaros
E
E
Somes
J
J
Lunec
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000737:chemistry / Q000473:pathology / Q000532:radiotherapy; D007822:Laryngeal Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000532:radiotherapy*; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000032:analysis*; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000737:chemistry / Q000473:pathology / Q000532:radiotherapy; D012189:Retrospective Studies; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53