Overexpression of p53 protein in squamous cell carcinomas of head and neck without apparent gene mutations Journal Article
| Authors: | Xu, L.; Chen, Y. T.; Huvos, A. G.; Zlotolow, I. M.; Rettig, W. J.; Old, L. J.; Garin-Chesa, P. |
| Article Title: | Overexpression of p53 protein in squamous cell carcinomas of head and neck without apparent gene mutations |
| Abstract: | Structural alterations of p53 and overexpression of the p53 protein are found in a large proportion of human cancers. In this study, we examined the frequency of p53 mutations and p53 overexpression in squamous cell carcinomas (SQCC) of head and neck. Expression of p53 was detected by immunohistochemistry (IHC) with monoclonal antibodies defining three distinct epitopes: PAb42l (species cross-reactive epitope on normal and mutated p53), PAbl801 (epitope on normal and mutated human p53). and PAb240 (conformational epitope of mutated p53 and denatured normal p53). Genetic alterations of p53 were identified by single-strand conformational polymorphism (SSCP) analysis and DNA sequencing in selected cases. IHC assays revealed nuclear p53 immu- nostaining in 53% of cases (32 of 60) with PAbl801, 38% (23 of 60) with PAb421, and 32% (19 of 60) with PAb240. Cases positive with PAb421 or PAb240 were also positive with PAbl801, whereas PAb421 and PAb240 identified overlapping but distinct tumor subsets. Areas of carcinoma in situ present in the tumor specimens showed nuclear p53 immunostaining in 11 of 26 cases. SSCP analysis for exons 5-9. the most common sites of p53 abnormalities, revealed mutations in 26% (15 of 58) of the evaluable cases. Comparison of the SSCP results with the IHC results for PAbl801 identified 11 cases that were positive by both methods, 4 cases with p53 mutations that were negative by IHC, 20 cases positive by IHC but without detectable p53 mutations, and 23 cases negative by both methods. IHC with PAb240, which is thought to be specific for mutated p53, was positive in 9 cases with demon- strable p53 mutations and in 9 cases with no detectable mutations. DNA sequence analysis of nine tumors identified point mutations, nonsense mutations, and frame- shift mutations. In conclusion, our study shows that p53 overexpression in SQCC of head and neck as detected by IHC is a frequent finding, and that overexpression is associated with common types of p53 mutations in some cases. However, IHC identifies p53 overexpression in some tumors with apparently normal SSCP patterns and, conversely, tumors with nonsense or frameshift mutations may not express any p53 detectable by IHC. © 1994 Raven Press. Ltd. |
| Keywords: | immunohistochemistry; controlled study; human tissue; major clinical study; frameshift mutation; mutation; clinical trial; squamous cell carcinoma; carcinoma, squamous cell; polymerase chain reaction; protein localization; controlled clinical trial; gene expression; protein p53; monoclonal antibody; molecular sequence data; tissue distribution; head and neck cancer; head and neck neoplasms; protein synthesis; epitope; tumor suppressor protein p53; base sequence; dna sequence; point mutation; protein determination; nonsense mutation; p53; dna probes; humans; human; priority journal; article; pcr-sscp |
| Journal Title: | Diagnostic Molecular Pathology |
| Volume: | 3 |
| Issue: | 2 |
| ISSN: | 1052-9551 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 1994-06-01 |
| Start Page: | 83 |
| End Page: | 92 |
| Language: | English |
| DOI: | 10.1097/00019606-199406000-00004 |
| PROVIDER: | scopus |
| PUBMED: | 8061893 |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- Source: Scopus |
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