Oral cancer is the sixth most common malignancy worldwide (1). The incidence of oral cancer in the world is much higher in South and South-East Asia with more than 100,000 cases occurring every year with poor survival rate (2). The major predisposing factors to oral cancer in this region are tobacco smok- ing and betel quid chewing (3,4). Oral carcinogenesis is a multi-step process involv- ing distinct genetic alterations. Chromosomal losses have been shown to occur at each histopathological step from benign hyperplasia to dysplasia to carcino- ma in situ to invasive head and neck cancers (5). In addition, clinically recognizable precursor lesions to oral carcinoma such as leukoplakia and erythroplakia occasionally occur. They are referred to as potential- ly malignant oral lesions (6). Histologic criteria used to predict the malignant potential of these lesions is termed epithelial dysplasia (7). The traditional histopathological diagnosis of potentially malignant oral lesions using dysplasia criteria has been shown to be highly subjective (8,9). The need for molecular markers to be used as an adjunct to histopathological assessment in predicting which potentially malignant oral lesion will transform to oral cancer has been well recognized (10). The checkpoint mechanisms that limit the replica- J. Exp. Clin. Cancer Res., 24, 4, 2005 639 Human Telomerase Reverse Transcriptase Expression in Oral Carcinogenesis - A Preliminary Report S.K.S. Kumar 1 , R.B. Zain 1 , S.M. Ismail 2 , S.C. Cheong 3 Dept. of Oral Pathology, Oral Medicine and Periodontology 1 , Dept. of Oral and Maxillofacial Surgery 2 , Faculty of Dentistry, University of Malaya, Kuala Lumpur; Cancer Research Initiatives Foundation (CARIF) 3 , Outpatient Centre, Subang Jaya Medical Centre, Subang Jaya, Selangor Darul Ehsan; Malaysia Human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, is strongly associated with telomerase activity implicated in cellular immortalization and tumorigenesis. In situ detection of hTERT will aid in determining the localization of telomerase positive cells. The aim of this study was to detect hTERT protein expression in multistep oral carcinogenesis using paraffin embedded tissue samples, and to study the relationship of hTERT expression with different histological stages in oral carcinogenesis. Normal (n=4), hyperplastic (n=4), dysplastic (n=4) and neoplastic (n=10) oral epithelia representing different histological stages in oral carcino- genesis were included in the study. hTERT protein detection was done by immunohistochemistry (IHC) tech- nique. Nuclear staining intensities were noted and the hTERT-labelling index was determined. Dysplastic and neoplastic oral epithelia showed an increased percentage of hTERT positive cells (Grade 4: >50% positive stain- ing nuclei) with intense staining in the basal, parabasal and superficial layers of the epithelia, unlike normal oral mucosa which showed intense staining only in the basal and parabasal cell layers, which are the normal prolifer- ative progenitor compartments. hTERT protein expression was elevated with the corresponding advancement of the histological stages of oral carcinogenesis, from normal to hyperplasia to dysplasia to carcinoma. There seems to be an upregulation of hTERT protein expression during the progression of oral cancer, therefore, this may in- dicate the feasibility of IHC detection of hTERT protein in oral carcinogenesis as a potential diagnostic or prog- nostic marker. Key Words: Telomerase, Human telomerase reverse transcriptase, Oral squamous cell carcinoma, Oral precancer, Immunohistochemistry