A Study On Expressions Of HTERT,c-myc And PCNA In Oral Leukoplakia And Oral Squamous Cell Carcinoma Of Human Oral Mucosa

Background and objectivesOral Leukoplakia (OLK) is the commonest premalignant disease in oral cavity. Oral squamous cell carcinoma (OSCC) is the commonest malignancy in oral cavity. There are 9%-19% patients of OLK will develop into OSCC. Although the assessment of malignant potential of OLK and the early diagnosis of OSCC are of important clinical significance, observer-independent histopathological criteria and early and sensitive markers of malignant potential are still unavailable. It is generally accepted that the carcinogenesis of OLK and OSCC is a multi-step process in which many genes may involve. Alteration of telomerase activity and the expression of c-myc gene may account for part of this process. A close correlation has been determined between the presence of human telomerase reverse transcriptase (hTERT) expression and telomerase activity. Recent researches have showed that the expression of hTERT is not only a good markerof many malignant tumors but also a marker of cell proliferation. hTERT protein and c-myc protein can reflect the expression of hTERT gene and c-myc gene, c-myc protein, a proto-oncogene product is related to cell proliferation and differentiation and its over-expression has been documented in various tumorous lesions. Recent studies have reported that c-myc protein directly activates telomerase transcription to induce telomerase activity. Proliferating cell nuclear antigen (PCNA) is a mature indicator of cell proliferation activity. With the goal of finding sensitive markers in carcinogenesis of oral mucosa and offering clues for clinical diagnosis and treatment, this paper studied expression of hTERT protein c-myc protein and PCNA in OLK and OSCC.MethodsEight-two cases of formalin-fixed, paraffin-embedded specimens from oral mucosa lesions were obtained from the pathology archive files of the Department of Pathology, the First Affiliated Hospital of Zhengzhou University. These specimens of OLK were divided into four groups: 15 cases of simple hyperplasia, 10 cases of mild dysplasia, 11 cases of moderate dysplasia and 9 cases of severe dysplasia. The specimens of OSCC were pathologically classified as 13 of grade I,12 of grade II, and 12 of grade III. 12 cases of specimens from oral normal mucosa were taken as control. Immunohistochemical detection for hTERT protein, c-myc protein and PCNA were carried out for all specimens. Then the expression rate of hTERT protein and c-myc protein and the proliferating index of PCNA were counted respectively. All data were analyzed statistically. Results1. None of normal controls showed positive hTERT protein staining. The strength of hTERT protein staining increased with the increasing cell proliferating degree. InOSCC, the strength of hTERT protein staining increased with the decreasing cell differentiation grade. The expression rates of hTERT protein in simple hyperplasia OLK, dysplasia OLK and OSCC were 26.67%(4/15), 56.67%(17/30) and 83.78% (31/37) respectively. The difference among them showed statistical significance (P<0.01). There were different staining patterns between simple hyperplasia OLK and dysplasia OLK.2. Normal control showed no positive c-myc protein staining. The expression rates of c-myc protein in simple hyperplasia OLK, dysplasia OLK and OSCC were 13.33% (2/15) , 36.37%(11/30) and 72.97% (27/31) respectively. There were statistical differences among them (P<0.01). But in dysplasia OLK, there were no differences among different groups (P>0.05). The different groups of OSCC also showed no statistical differences (P>0.05).3. Although all specimens demonstrated PCNA-positive staining, there were significantly different PCNA-proliferating index increased as normal oral mucosa progressed to OLK and to OSCC. Additionally, it was found that there were different staining patterns in oral normal mucosa, simple hyperplasic OLK, dysplasia OLK and OSCC.4. All specimens were classified as hTERT-positive group and hTERT-negative group according to hTERT protein...