title: Expression pattern of Notch intracellular domain (NICD) and Hes-1 in preneoplastic and neoplastic human oral squamous epithelium: their correlation with c-Myc, clinicopathological factors and prognosis in Oral cancer.
abstract: Notch pathway molecules crosstalk with Wnt/β-catenin signaling cascade in stem cells and tumors. However, the correlation between the expression pattern of Notch intracellular domain NICD, Hes-1 and c-Myc has not been studied in oral squamous cell carcinoma. The aim of this study is to investigate the correlation and prognostic significance of NICD, Hes-1 and c-Myc in oral cancer. Immunohistochemistry was used to study the expression pattern of NICD, Hes-1 and c-Myc in oral preneoplastic and neoplastic tissues. In addition, double immunofluorescence was used to examine the co-localization of NICD, Hes-1 and c-Myc in H314 cells. The expression pattern of NICD and Hes-1 was gradually increased from normal to dysplasia to carcinoma. Interestingly, statistically significant correlation was not observed between NICD, Hes-1 and c-Myc in oral squamous cell carcinoma. Furthermore, NICD+/c-Myc+ and Hes-1+/c-Myc+ double positive cases showed worst survival when compared with other cases in oral cancer. Notch signaling molecules, NICD and Hes-1, are found to be involved in the progression of oral squamous cell carcinoma. Interestingly, NICD, Hes-1 and c-Myc may have independent roles in oral cancer. On the other hand, we have demonstrated that NICD+/c-Myc+ and Hes-1+/c-Myc+ double positivity might be used as independent prognostic indicator of oral carcinoma.
authors.affiliation: Unit of Biochemistry, Department of Zoology, University of Madras, Guindy Campus, Chennai, Tamil Nadu, India.
authors.forename: Ravindran
authors.initials: R
authors.lastname: Gokulan
authors.forename: Devaraj
authors.initials: D
authors.lastname: Halagowder
mesh_terms: D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D064231:Nestin / Q000378:metabolism; D011230:Precancerous Conditions / Q000473:pathology; D017434:Protein Structure, Tertiary; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D012016:Reference Values; D016019:Survival Analysis; D000072056:Transcription Factor HES-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D064231:Nestin; D016271:Proto-Oncogene Proteins c-myc; D051880:Receptors, Notch; D000072056:Transcription Factor HES-1; C489427:MYC protein, human; C577484:NES protein, human; C078493:HES1 protein, human