Molecular and immunological aspects of p53 and p53-autoantibodies in head and neck squamous cell carcinoma.
The tumour suppressor protein p53 (wild-type = wt-p53) is of major importance in the genetic integrity of the cell. Mutations of the p53-gene (mt-p53) are the most frequent genetic aberrations identified in different tumour entities. As analyzed in a wide variety of human malignomas, mt-p53 evokes a specific immune response. Yet, the possible occurrence of p53-autoantibodies in patients with head and neck squamous cell carcinomas (HNSCC) correlated to p53-mutations, p53 in sera and p53-overexpression in tissue has not been previously investigated. For the first time, the p53 status in 24 HNSCC patients was analyzed in the present study. The following parameters were investigated: analysis of mutation frequency of the p53-gene by direct sequencing of the exons 5-9, immunohistochemical detection of p53, measurement of the wt- and mt-p53-protein in sera by ELISA and p53-autoantibodies in sera by ELISA. Mutations of the p53-gene were detected in four (17%) patients. Overexpression of wt-p53 was detected by immunohistochemistry in 18 out of 24 (75%) tumours. In 8 (33%) patients the p53-protein was also detectable in sera, whereas in just one of these eight patients p53-autoantibodies were detectable simultaneously. Overall 6 out of 24 (25%) patients were found to be positive for serum p53-autoantibodies. Of these 6 cases, 5 could be assigned to tumours with immunohistochemically measurable wt-p53-overexpression. There was no correlation between p53-overexpression in tissue and p53-protein levels in sera or between p53-autoantibody levels in sera, nor in mutation frequency of the p53-gene and p53-overexpression in tissue. The results presented herein support the hypothesis that strong accumulation of p53 in the tissue is an important prerequisite for development of p53-autoantibodies. However, there must be further, yet unknown factors that influence the p53-autoantibody production because p53-autoantibodies were not identified in sera in each case of p53-accumulation in the tissue.
Cordes
Christian
C
Department of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts-University Kiel, Kiel, Germany. ccordes@hno.uni-kiel.de
Von Lingen
J
J
Görögh
T
T
Ambrosch
P
P
Gottschlich
S
S
Hoffmann
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000737:chemistry*; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism*; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000235:genetics*
D001323:Autoantibodies; D016159:Tumor Suppressor Protein p53