Expression of p53 in leukoplakia and squamous cell carcinoma of the oral mucosa: correlation with expression of Ki67

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% ofcells. 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% Of the pre-malignant lesions, oral leukoplakia has greatest relevance in the study of the biology of carcinogenesis because the oral cavity is easily accessible for clinical examination4 and also because it has a multistage carcinogenesis pathway and of the concept of field cancerisation.' The oral carcinogenesis pathway can be broadly classified histopathologically into normal, non-dysplastic, dysplastic, carcinoma-insitu, and invasive carcinoma.4 Molecular biological studies on oral cancer have identified several genetic aberrations in the cells during various tumour stages.6 7Mutations in the p53 tumour suppresser gene are the most common genetic changes in humans cancers and are regarded as early events in carcinogenesis.8"-In pre-malignant and malignant oral lesions, alterations in p53 expression have been reported both at protein and DNA levels.12-18 As cancer is characterised by uncontrolled cell proliferation, markers of proliferation, such as Ki67 and proliferating cell nuclear antigen, have been studied extensively in neoplastic lesions.'9 Ki67 is a nuclear antigen which is present in the perichromosomal region during mitosis and seems to be a non-histone protein, representing a new class of cell cycle maintaining proteins.20 Studies on proliferation markers in lesions of the oral mucosa have shown that expression of Ki67 is correlated with the severity of the lesion. [21][22][23][24] Studies on the relation between p53 and the proliferation index in various malignancies, including lesions of the oral mucosa, have been reported previously.25"-Our aim was to elucidate the relation, if any, between expression of p53 and Ki67 in normal, non-dysplastic, dysplastic, and neoplastic lesions of the oral mucosa and to determine whether these markers have potential as early indicators of malignancy. MethodsFifty tissue samples, five of normal oral mucosa, 30 of leukoplakia and 15 of invasive carcinoma, were studied. Demographic details were recorded for all patients and included age, sex and whether they used tobacco products. Only those patients with oral leukoplakia and carcinoma at non-keratinising sites of the oral cavity were included. A 4 mm punch biopsy specimen was collected from each patient, immediately snap frozen and stored in liquid nitrogen. Cryostat sections, 5 ,um thick, were cut from each biopsy specimen and fixed in cold acetone. One section from each biopsy

Assessment of Cellular Proliferation in Oral Verrucous Carcinoma and Well-Differentiated Oral Squamous Cell Carcinoma Using Ki67: A Non-Reliable Factor for Differential Diagnosis?

“…We suggest that EGFR and P53 may have more important role in cell transformation than proliferation in two carcinomas because of: Activation of EGFR down-stream signaling pathways such as ERK1 and ERK2 are important for expression of the invasive phenotype and different staining patterns of ERK1 and ERK2 has been reported between OVC and well-differentiated OSCC (Lessard et al,2001;Ono et al,2002).Whereas, cyclinD1 expression , as a potential proliferative marker and one of the other downstream targets of EGFR , was not different between them (Angadi and Krishnapillai,2007 ;Suomela et al, 2009). Furthermore, the expression of p53 occasionally can have no correlation with Ki67 expression (Kannan et al,1996). Based on Our results , lack of different level and pattern of Ki67 expression between the studied tumors may be correlated with the similar histopathologic grade of them and it seems evaluation of proliferative activity ( with utilized antibody) is useless as a marker for discovering the biological behavior and differentional diagnosis of these variants of OSCC with similar grade.…”

Leuloplakia - Review of A Potentially Malignant Disorder

“…Zhang and Rosin reviewed the loss of heterozygosity in oral leukoplakia and categorized leukoplakia into high risk (loss from 3p and or 9p and loss from one or more of the 4q, 8p, 11q, 13q, and 17p chromosomes), intermediate risk (loss from 3p and or 9p) and low risk (no loss seen). High risk and intermediate risk lesions showed a 33 and 3.8 times chances of malignant transformation respectively than low risk lesions [16,18].…”

“…They categorized dysplastic leukoplakias in to high risk (aneuploid lesions), intermediate risk (Tetraploid lesions) and low risk (diploid lesions). Further studies in larger samples must be carried out to determine the significance of this promising marker [16,18].…”

“…These lesions have been shown to have a higher malignant transformation rates [17,18]. associated with this lesion.…”

“…But it was found that some dysplastic leukoplakias may remain unchanged or subside with time. Hence, few other parameters like DNA ploidy, p53 expression, HPV subtypes presence, and markers like podoplanin have been used to know the transformation rate and thus the prognosis of the lesion [16,18].…”