Overexpression of p53-related proteins predicts rapid growth rate of head and neck cancer.
OBJECTIVE
The p53 tumor suppressor gene plays an important role for cell cycle regulation and is the most frequent mutated gene in head and neck cancer. Controversy remains regarding the biological and clinical value of immunohistochemical identification of the proteins accumulated in association with inactivation of the p53 gene and increased tumor growth. Therefore, the objective of the present study was to perform a cell kinetic analysis of cases with untreated squamous cell carcinoma and to compare the result with immunostaining for p53-related proteins in the tumor cells.


METHODS
A prospective series of 32 patients presenting with various stages of untreated squamous cell carcinoma of the head and neck were included. Bromodeoxyuridine (BrdU) was injected as a tracer dose before tumor biopsy for cell kinetic analysis, and p53 protein accumulation was detected using two antibodies (DO7 and PAb 1801).


RESULTS
Antibody DO7 showed the highest and the optimal immunoreactivity. Diploid tumors were found in 27 cases (84%), and the mean potential doubling time (Tpot) was 55 +/- 7 hours for these tumors. Positivity of DO7 (>1%) was demonstrated in 85% of the cases. However, a discrimination level exceeding 20% was required to obtain a significant negative relationship (Spearman's rank correlation coefficient test, P < or = .03) between Tpot and DO7 positivity. At that level, 33% of the tumors remained DO7-positive. The corresponding Tpot was not significantly different from the overall mean. The rates of metastatic disease and survival were not dependent on DO7 immunoreactivity or cancer cell kinetics.


CONCLUSIONS
Accumulation of p53-related proteins is associated with an unrestrained growth of head and neck cancer.
Edström
S
S
Department of Otoalryngology-Head and Neck Surgery, Sahlgrenska University Hospital, Göteborg, Sweden.
Cvetkovska
E
E
Westin
T
T
Young
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D000911:Antibodies, Monoclonal; D000963:Antimetabolites; D001973:Bromodeoxyuridine; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology* / Q000556:secondary; D002452:Cell Count; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation; D002863:Chromogenic Compounds; D004396:Coloring Agents; D004171:Diploidy; D005260:Female; D005434:Flow Cytometry; D005544:Forecasting; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000276:immunology
D000911:Antibodies, Monoclonal; D000963:Antimetabolites; D002863:Chromogenic Compounds; D004396:Coloring Agents; D016159:Tumor Suppressor Protein p53; D001973:Bromodeoxyuridine