Published by : PROFESSIONAL MEDICAL PUBLICATIONS
|January - March 2008||
p53 Expression in benign, dysplastic and
malignant oral squamous epithelial lesions
Suchita Panjwani1, Saleem Sadiq2
Objective: To observe the frequency of benign, dysplastic and malignant oral squamous epithelial lesions and to calculate p53 expression in these lesions.
Methodology: This was a retrospective study. All the oral biopsies received during the period 1st July 2000 to 30th June 2005 were reviewed. Histopathological parameters were noted. Immunohistochemical staining was performed to see the p53 expression in these lesions.
Results: There was a single case of benign lesion/papilloma, which showed basal p53 immunoexpression. The dysplastic lesions account for 10 cases. p53 immunoexpression was positive in 75% cases of the dysplastic lesions. Squamous cell carcnoma was found to be the commonest malignant oral epithelial lesions accounting for 412 cases. Malignancy grading was also performed which showed maximum number of cases between score of 9-12. p53 immunoexpression was found positive in 76.8% cases of squamous cell carcinoma.
Conclusion: Squamous Cell Carcinoma (SCC) was found to be the commonest oral malignant epithelial lesion. p53 immunoexpression was found in 76.8% cases of oral squamous cell carcinoma. The p53 immunopositivity was increasing as the grade score was rising but decreasing further as the tumor became poorly differentiated. Combining histological analysis with p53 immunoexpression, evaluation of dysplastic lesions could be improved.
KEY WORDS: Squamous cell carcinoma, p53.
Pak J Med Sci January - March 2008 Vol. 24 No. 1 130-135
1. Dr. Suchita Panjwani
2. Prof. Saleem Sadiq,
1-2: Basic Medical Sciences Institute,
Jinnah Postgraduate Medical Centre,
Karachi - Pakistan.
Email: ss_ email@example.com
Dr. Suchita Panjwani
Flat #504, Mehran Estate Apartments,
Dawood pota Road, Cantt.
Karachi - Pakistan.
* Received for Publication: May 4, 2007
* Accepted: January 5, 2008
The concept of a step wise development of cancer in the oral mucosa, i.e., the initial presence of a precursor (pre-malignant, pre-cancerous) lesion subsequently developing into cancer is well established. The term ‘epithelial dysplasia’ is assigned to histopathological changes associated with an increased risk of progressing to malignant stage (i.e, squamous cell carcinoma). The presence of epithelial dysplasia may be even more important in predicting malignant development than the clinical characterstics.1
The mutations in the p53 (also known as Tp53) gene and its alteration in the p53 protein resulting in its accumulations in cells may play critical role in tumorigenesis.2 It has been reported that immunoreactivity for p53 protein can be detected in benign tumors and premalignant lesions, including dysplasia of the oral mucosa.3 p53 alterations can occur early in carcinogenesis and that these alterations are maintained upon progression to overt malignancy.4 Infact oral cancer may provide an even better model for the study of multistage tumor igenesis because the lesions are easily detected early, are frequently diagnosed at the pre invasive stage, are accessible to biopsy and are amenable to accurate follow up evaluation.5,6
MATERIALS AND METHODS
This was a retrospective study carried out in the Department of Pathology, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Center, Karachi. All the oral biopsies received over a period of five years 1st July 2000 to 30th June 2005 were reviewed. All the neoplastic oral epithelial lesions were identified. Modified malignancy grading of squamous cell carcinomas was performed on the invasive front.7 The malignant lesions showing only tumor tissue were excluded for grading purpose.
Immunohisto chemistry:Section of 5um were cut from formalin fixed, paraffin embedded tissues and were mounted on silane coated slides. Antigen retrieval was performed in citrate by pressure cooker technique. A mouse monoclonal antibody recognizing both wild and mutant type p53 (Ready to use clone DO-7, Labvision, USA) was used as the primary antibody. Sections where the primary antibody had been omitted served as negative controls and known p53 positive colon cancer was used as the positive control.
Quantification of Immunohistochemistry results:
For benign and dysplastic lesions three categories were defined, namely:
1. Negative, no nuclear p53 staining detected in any epithelial cell.
2. Basal, nuclear p53 staining confined to the basal epithelial layer.
3. Suprabasal, nuclear p53 staining in (basal and) suprabasal epithelial layers.
For malignant lesions also three categories were defined, namely:
1. Negative, no nuclear staining in any tumor cell.
2. +, nuclear p53 staining in less than 25% tumor cells.
3. ++, nuclear p53 staining in more than 25% tumor cells.
In our series there were 412 malignant oral epithelial lesions followed by 10 dysplastic lesions and a single case of a benign lesion (Table-I). Oral epithelial lesions were common in 5th decade of life in males and 4th decade in females. In most of the cases site of the lesion was not specified. Excluding that tongue was the common site of lesion.
There was only a single case of benign lesion i.e. verruca vulgaris (Figure-1),
which showed basal p53 immunoexpression (Table-II). However, dysplastic lesion accounts for 10 cases. Out of these three exhibit morphologically papillary pattern with keratosis, parakeratosis and dysplasia while five cases show simple keratosis with mild dysplasia. There were two cases showing features of verrucous hyperplasia (Figure-2). p53 immunopositivity was seen in 8 cases of dysplasia, which showed 75% immunopositivity.
Squamous cell carcinoma (Figure-3) was found to be the commonest neoplastic oral squamous epithelial lesion. There were 379 (92%) cases SCC, NOS. Its variants accounts for 30(7.2%) cases of verrucous carcinoma. One (0.2%) case each of basaloid, papillary and acantholytic SCC was seen (Table-III). Squamous Cell Carcinoma (SCC) was predominantly seen in males. The male to female ratio in our study was 1.19:1. The mean age of the patients was 49.9 years. The peak malignancy score that showed maximum number of cases expressing p53 immunopositivity was 9-12.
In our study the p53 immunoexpression by IHC analysis in SCC was seen in 76.8% cases. There were 147(46.5%) cases showing ++ p53 immunopositivity (Fig-4), 93(29.4%) were + positive while 76(24%) cases stained negative for p53 (Table-IV).
In our series benign lesions are rare, as only a single case of verruca vulgaris was seen. The p53 immunoexpression in the benign lesion showed basal positivity. No study was found for comparison. However p53 localization was seen in the 75% of the dysplastic lesions. p53 overexpression has been reported with considerable variation in patient population with oral dysplastic lesions from as low as 0% by Ogden et al8 to a high 55% by Kerdpon et al9 Ravi et al10 reported p53 expression in 82% cases with minimal dysplasia whereas Kaur et al3 reported p53 over expression in 55% cases of dysplasia.
Oral leukoplakia is a premalignant lesion that has been considered to confer increased risk for development of oral cancer.11,12 It should be emphasized that leukoplakia is a clinical term and its use carries no implication with regard to the histological findings. However, it is recommended that a histological report should always include a statement on the presence or absence of epithelial dysplasia and if present, the assessment of its severity.13 There were two cases showing features of verrucous hyperplasia. Verrucous hyperplasia is the forerunner of verrucous carcinoma and the transition is so consistent that the hyperplasia, once diagnosed should be treated like verrucous carcinoma.13
The most common neoplastic oral epithelial lesion in our study was squamous cell carcinoma. The male to female distribution in our study is 1.19:1 that is in accordance by Pinholt et al.14 However the studies in Greek and Brazilian population show quiet a higher ratio of 9.2:1 and 4.8:1 respectively.15,16 The average age was 49.9 years that was lower than the one reported by Gervasio et al.16 i.e. 58.6 years and Mirza et al17 i.e. 54.3%.
Jafarey and Zaidi18 reported 13% of the cases below the age of 40 years and 0.5 % of the cases were below the age of 20 years. Comparing these results after three decades to our study there is significant rise in oral cancer i.e. 34 % of the cases were below the age of 40 years and 1.9 percent patients were below the age of 20 years. This could be attributed to the fact that children come in contact with pan and tobacco (supari) especially in lower socioeconomic group at very young age so that exposure to carcinogens starts at early age.
Epidemiological studies have shown that the site of occurrence for oral cancer differs widely. Tongue, lip and floor of mouth are the most frequent sites of lesions of squamous cell carcinoma in the oral cavity.16 In our study excluding the cases in which site was not specified, the tongue is the most commonest site of lesion. There is a slight male predominance in our study, which is in accordance to the other studies in Pakistan and Western countries.19,20
We also attempted to do the histopathologic grading of squamous cell carcinoma, which is a modification of a method recommended by Anneroth et al.21 The cases were separated into three groups which had significantly different prognosis: score 5-8, 9-12 and 13-20 is the total malignancy score representing 19.6%, 49% and 31.3% which varies markedly from that reported by Bryne et al7 who found malignancy score representing 82%, 26% and 16% respectively in their study.
In our study the expression of p53 by IHC analysis in SCC was seen in 76.8% cases. Our findings are in agreement with Kaur3 and Mirza17 who found p53 immunoexpression in 75% and 73.8% oral squamous cell carcinomas. Langdon and Partridge5 showed 80% of oral cancer patients from United Kingdom with p53 expression. However other workers found lower frequency of p53 immunoexpression i.e. 45% by Yan et al.22 46% by Saranath el at.23 36% by Pillay et al.24 Our findings show that site, age and sex did not influence p53 expression that is in accordance with other studies.5,19
There was increase in p53 immunoexpression as the malignancy score rises from 5-8 to 9-12, however this is further followed by decrease in p53 expression as the score rises further i.e. 13-20 showing statistically significant P value.
Squamous cell carcinoma was the commonest malignant oral epithelial lesion. Malignancy scoring should be performed at the invasive front of the carcinoma so that histological parameters may properly be assessed. p53 immunoexpression was present in 76% cases of squamous cell carcinoma. No correlation of p53 immunoreactivity with age, sex and site was found. The immunopositivity was increasing as the malignancy score was raising but decreasing further as the tumor became poorly differentiated. Dysplastic lesions also showed p53 immunoexpression in 75% cases. Based on these findings combining histological analysis with p53 immunoexpression, evaluation of dysplastic lesions could be improved.
1. Reibel J. Prognosis of oral premalignant lesions. Significance of clinical, histopathological, and molecular biological characterstics. Crit Rev Oral Biol Med 2003;14(1):47-62.
2. Levine AJ. p53, the cellular gate keeper for growth and division. Cell 1997; 88:323-31.
3. Kaur J, Srivastva A, Ralhan R. Overexpression of p53 protein in betel and tobacco related human oral dysplasia and squamous cell carcinoma. Int J Cancer 1994;58:340-5.
4. Cruz IB, Snijders PJ, Meijer CJ. P53 immunoexpression in non-malignant oral mucosa adjacent to oral squamous cell carcinoma, potential consequences for clinical management. J Pathol 2000;191:132-7.
5. Langdon JD, Partridge M. Expression of the tumor suppressor gene p53 in oral cancer. British J Oral Maxillofacial Surg 1992;30:214-20.
6. Nylander K, Steining R, Gustafsson H. p53 expression and cell proliferation in squamous cell carcinoma of the head and neck. Cancer 1995;75:87-93.
7. Bryne M, Koppang HS, Lilleng R, Stem Tbag G, Dabelsteen E. New malignancy grading is a better prognostic indicator than Broders grading in Oral squamous cell carcinomas. J Oral Pathol Med 1989;18(8): 432-7.
8. Ogden GM, Kiddie RA, Lunny DP, Lane AP. Assessment of p53 protein expression in normal, benign and malignant oral mucosa. J Pathol 1992;166:389-94.
9. Kerdpon D, Rich AM, Reade PC. Expression of p53 in oral mucosal hyperplasia, dysplasia and squamous cell carcinoma. Oral Diseases1997;3:86-92.
10. Ravi D, Kumari N, Rajaran RS, Nair MK, Pillai MR. Expression of programmed cell death regulatory p53 and bcl2 protein in oral lesions. Cancer letters 1996;105:139-46.
11. Silverman S Jr, Gorsky M. Epidemiologic and demographic update in oral cancer: California and national data-1973to 1985. J Am Dent Assoc 1990;120:523-4.
12. Krammer IR, Lucas RB, Pindborg JJ, Sobin LH. Definition of leukoplakia and related lesions; an aid to studies on oral precancer. Oral Surg Oral Med Oral Pathol 1978;46:518-39.
13. Shafer WG, Hine MK, Levy BM. Benign and malignant tumors of oral cavity. In Rajendran R, Sivapathasundharan B (eds) A textbook of oral pathology5th ed, Elseiver, New Dehli 2005;121-36.
14. Pinholt EM, Rindum J, Pindborg JJ. Oral cancer: a retrospective study of 100 Danish cases. Br J Oral Maxillofac Surg 1997;35:77-80.
15. Antoniades DZ, Stynidis K, Papanatou P, Trigonidis G. Squamous cell carcinoma of the lips in a northern Greek population. Evaluation of prognostic factors on 5-year survival rate-I. Oral Oncol Eur J Cancer B 1995;31B:333-9.
16. Gervasio OLAS, Dutra RA, Tartaglia SMA, Vasconcellos WA, Barbosa AA, Aguiar MCF. Oral squamous cell carcinomas: A retrospective study of 740 cases in Brazilian population. Braz Dent J 2001;12(1):57-61.
17. Mirza T, Alam SM, Pringle IL, Zaidi SH. Molecular analysis of human papillomavirus and oncosuppressor genes in tobacco related oral cancer. Pak J Otolaryngol 1998;14:27-33.
18. Jafarey NA, Zaidi SHM. Final report of the oral carcinoma research project. Jinnah Postgraduate Medical Center, 1974.
19. IARC. Tobacco habits other than smoking; betel quid and areca nut chewing and some related nitrosamines. IARC monograph on the evaluation of the carcinogenic risk of chemicals to humans. 37 IARC, Lyon 1985.
20. Blot WI, Devesa SS, Mclaughlin JK. Oral and pharyngeal cancer. Cancer Survey 1994;19/20:23-42.
21. Anneroth G, Batsakis J, Luna M. Review of the literature and a recommended system of malignancy grading in oral squamous cell carcinoma. Scand J Dent Res 1987;95(3):229-49.
22. Yan JJ, Tzeng CC, Jin YT. Overexpression of p53 protein in squamous cell carcinoma of buccal mucosa and tongue in Taiwan; an immunohistochemical and clinicopathological study. J Oral Pathol Med 1996;25:55-9.
23. Saranath D, Tandle AT, Teni TR, Dedhia PM, Borges AM, Parikh D, et al. p53 inactivation in chewing tobacco-induced oral cancers and leukoplakias from India. Oral Oncol 1999;35:242-50.
24. Pillay M, Vasudevan DM, Rao CP, Vidya M. p53 expression in oral cancer: observations of a South Indian study. J Exp Clin Cancer Res 2003;22(3):447-51.
HOME | SEARCH | CURRENT ISSUE | PAST ISSUES
Room No. 522, 5th Floor, Panorama Centre
Building No. 2, P.O. Box 8766, Saddar, Karachi - Pakistan.
Phones : 5688791, 5689285 Fax : 5689860