Abstract
Aim—To study p53 expression in relation to proliferative status in normal and nondysplastic, dysplastic and malignant lesions of the oral mucosa.
Method—The standard avidin-biotin complex (ABC) immunohistochemical staining method was used to study the expression of p53 and Ki67 on frozen sections of oral leukoplakias and carcinomas.
Results—Of the leukoplakia and carcinoma samples, 70% expressed p53 in over 5% of cells. In normal mucosa less than 5% of cells expressed p53. The proliferation index, as assessed by expression of Ki67, was highest in the malignant lesions (43%) and lowest in normal mucosa (11%). Statistical analysis revealed that expression of both p53 and Ki67 was correlated significantly with the histopathological stage of the tumour. However, expression of p53 was not correlated with that of Ki67. In leukoplakia lesions with proliferative features p53 immunostaining was less intense than in non-proliferative lesions; this difference was statistically significant.
Conclusions—These results emphasise the potential of Ki67 and p53 as biomarkers of carcinogenesis in oral cancer and may also serve as intermediate points for cancer prevention programmes, such as the oral chemopreventive trials. Factors other than p53 may have a more important role in the deregulation of proliferation in pre-malignant oral lesions.
Keywords: p53
Keywords: Ki67
Keywords: oral leukoplakia
Keywords: oral squamous cell carcinoma
Keywords: tumour progression
Keywords: immunohistochemistry
Full text
PDF





Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ahomadegbe J. C., Barrois M., Fogel S., Le Bihan M. L., Douc-Rasy S., Duvillard P., Armand J. P., Riou G. High incidence of p53 alterations (mutation, deletion, overexpression) in head and neck primary tumors and metastases; absence of correlation with clinical outcome. Frequent protein overexpression in normal epithelium and in early non-invasive lesions. Oncogene. 1995 Mar 16;10(6):1217–1227. [PubMed] [Google Scholar]
- Ames B. N., Gold L. S., Willett W. C. The causes and prevention of cancer. Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5258–5265. doi: 10.1073/pnas.92.12.5258. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Begg AC. Critical Appraisal of In Situ Cell Kinetic Measurements as Response Predictors in Human Tumors. Semin Radiat Oncol. 1993 Apr;3(2):144–151. doi: 10.1054/SRAO00300144. [DOI] [PubMed] [Google Scholar]
- Coles C., Condie A., Chetty U., Steel C. M., Evans H. J., Prosser J. p53 mutations in breast cancer. Cancer Res. 1992 Oct 1;52(19):5291–5298. [PubMed] [Google Scholar]
- Decter M. Structuring medical manpower: the Canadian response. J R Soc Med. 1995;88 (Suppl 26):35–47. [PMC free article] [PubMed] [Google Scholar]
- Girod S. C., Krueger G., Pape H. D. p53 and Ki 67 expression in preneoplastic and neoplastic lesions of the oral mucosa. Int J Oral Maxillofac Surg. 1993 Oct;22(5):285–288. doi: 10.1016/s0901-5027(05)80517-x. [DOI] [PubMed] [Google Scholar]
- Girod S. C., Krämer C., Knüfermann R., Krueger G. R. p53 expression in the carcinogenesis in the oral mucosa. J Cell Biochem. 1994 Dec;56(4):444–448. doi: 10.1002/jcb.240560404. [DOI] [PubMed] [Google Scholar]
- Girod S. C., Pape H. D., Krueger G. R. p53 and PCNA expression in carcinogenesis of the oropharyngeal mucosa. Eur J Cancer B Oral Oncol. 1994 Nov;30B(6):419–423. doi: 10.1016/0964-1955(94)90023-x. [DOI] [PubMed] [Google Scholar]
- Hall P. A., McKee P. H., Menage H. D., Dover R., Lane D. P. High levels of p53 protein in UV-irradiated normal human skin. Oncogene. 1993 Jan;8(1):203–207. [PubMed] [Google Scholar]
- Kaur J., Srivastava A., Ralhan R. Overexpression of p53 protein in betel- and tobacco-related human oral dysplasia and squamous-cell carcinoma in India. Int J Cancer. 1994 Aug 1;58(3):340–345. doi: 10.1002/ijc.2910580305. [DOI] [PubMed] [Google Scholar]
- Levine A. J., Perry M. E., Chang A., Silver A., Dittmer D., Wu M., Welsh D. The 1993 Walter Hubert Lecture: the role of the p53 tumour-suppressor gene in tumorigenesis. Br J Cancer. 1994 Mar;69(3):409–416. doi: 10.1038/bjc.1994.76. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nylander K., Nilsson P., Mehle C., Roos G. p53 mutations, protein expression and cell proliferation in squamous cell carcinomas of the head and neck. Br J Cancer. 1995 Apr;71(4):826–830. doi: 10.1038/bjc.1995.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nylander K., Stenling R., Gustafsson H., Zackrisson B., Roos G. p53 expression and cell proliferation in squamous cell carcinomas of the head and neck. Cancer. 1995 Jan 1;75(1):87–93. doi: 10.1002/1097-0142(19950101)75:1<87::aid-cncr2820750115>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
- Ranasinghe A. W., Warnakulasuriya K. A., Johnson N. W. Low prevalence of expression of p53 oncoprotein in oral carcinomas from Sri Lanka associated with betel and tobacco chewing. Eur J Cancer B Oral Oncol. 1993 Apr;29B(2):147–150. doi: 10.1016/0964-1955(93)90038-g. [DOI] [PubMed] [Google Scholar]
- Ranasinghe A., MacGeoch C., Dyer S., Spurr N., Johnson N. W. Some oral carcinomas from Sri Lankan betel/tobacco chewers overexpress p53 oncoprotein but lack mutations in exons 5-9. Anticancer Res. 1993 Nov-Dec;13(6A):2065–2068. [PubMed] [Google Scholar]
- Regezi J. A., Zarbo R. J., Regev E., Pisanty S., Silverman S., Gazit D. p53 protein expression in sequential biopsies of oral dysplasias and in situ carcinomas. J Oral Pathol Med. 1995 Jan;24(1):18–22. doi: 10.1111/j.1600-0714.1995.tb01124.x. [DOI] [PubMed] [Google Scholar]
- Saranath D., Chang S. E., Bhoite L. T., Panchal R. G., Kerr I. B., Mehta A. R., Johnson N. W., Deo M. G. High frequency mutation in codons 12 and 61 of H-ras oncogene in chewing tobacco-related human oral carcinoma in India. Br J Cancer. 1991 Apr;63(4):573–578. doi: 10.1038/bjc.1991.133. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schlüter C., Duchrow M., Wohlenberg C., Becker M. H., Key G., Flad H. D., Gerdes J. The cell proliferation-associated antigen of antibody Ki-67: a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins. J Cell Biol. 1993 Nov;123(3):513–522. doi: 10.1083/jcb.123.3.513. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scully C., Burkhardt A. Tissue markers of potentially malignant human oral epithelial lesions. J Oral Pathol Med. 1993 Jul;22(6):246–256. doi: 10.1111/j.1600-0714.1993.tb01066.x. [DOI] [PubMed] [Google Scholar]
- Scully C. Oncogenes, tumor suppressors and viruses in oral squamous carcinoma. J Oral Pathol Med. 1993 Sep;22(8):337–347. doi: 10.1111/j.1600-0714.1993.tb01086.x. [DOI] [PubMed] [Google Scholar]
- Shin D. M., Hittelman W. N., Hong W. K. Biomarkers in upper aerodigestive tract tumorigenesis: a review. Cancer Epidemiol Biomarkers Prev. 1994 Dec;3(8):697–709. [PubMed] [Google Scholar]
- Shin D. M., Kim J., Ro J. Y., Hittelman J., Roth J. A., Hong W. K., Hittelman W. N. Activation of p53 gene expression in premalignant lesions during head and neck tumorigenesis. Cancer Res. 1994 Jan 15;54(2):321–326. [PubMed] [Google Scholar]
- Shin D. M., Voravud N., Ro J. Y., Lee J. S., Hong W. K., Hittelman W. N. Sequential increases in proliferating cell nuclear antigen expression in head and neck tumorigenesis: a potential biomarker. J Natl Cancer Inst. 1993 Jun 16;85(12):971–978. doi: 10.1093/jnci/85.12.971. [DOI] [PubMed] [Google Scholar]
- Slootweg P. J., Koole R., Hordijk G. J. The presence of p53 protein in relation to Ki-67 as cellular proliferation marker in head and neck squamous cell carcinoma and adjacent dysplastic mucosa. Eur J Cancer B Oral Oncol. 1994;30B(2):138–141. doi: 10.1016/0964-1955(94)90066-3. [DOI] [PubMed] [Google Scholar]
- Thomas S., Brennan J., Martel G., Frazer I., Montesano R., Sidransky D., Hollstein M. Mutations in the conserved regions of p53 are infrequent in betel-associated oral cancers from Papua New Guinea. Cancer Res. 1994 Jul 1;54(13):3588–3593. [PubMed] [Google Scholar]
- Tsuji T., Sasaki K., Kimura Y., Yamada K., Mori M., Shinozaki F. Measurement of proliferating cell nuclear antigen (PCNA) and its clinical application in oral cancers. Int J Oral Maxillofac Surg. 1992 Dec;21(6):369–372. doi: 10.1016/s0901-5027(05)80765-9. [DOI] [PubMed] [Google Scholar]
- Valente G., Orecchia R., Gandolfo S., Arnaudo M., Ragona R., Kerim S., Palestro G. Can Ki67 immunostaining predict response to radiotherapy in oral squamous cell carcinoma? J Clin Pathol. 1994 Feb;47(2):109–112. doi: 10.1136/jcp.47.2.109. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Warnakulasuriya K. A., Johnson N. W. Association of overexpression of p53 oncoprotein with the state of cell proliferation in oral carcinoma. J Oral Pathol Med. 1994 Jul;23(6):246–250. doi: 10.1111/j.1600-0714.1994.tb00053.x. [DOI] [PubMed] [Google Scholar]
- Warnakulasuriya K. A., Johnson N. W. Expression of p53 mutant nuclear phosphoprotein in oral carcinoma and potentially malignant oral lesions. J Oral Pathol Med. 1992 Oct;21(9):404–408. doi: 10.1111/j.1600-0714.1992.tb01028.x. [DOI] [PubMed] [Google Scholar]
- Zoeller J., Flentje M., Sinn P., Born I. A. Evaluation of AgNOR and Ki-67 antigen as cell kinetic parameters in oral dysplasias and carcinomas. Anal Cell Pathol. 1994 Jul;7(1):77–88. [PubMed] [Google Scholar]


