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.

Does Notch play a tumor suppressor role across diverse squamous cell carcinomas?

“…This concept may need to be further validated with the studies targeting SCCs from other tissues, such as lung and cervical whose molecular pathogenesis remains poorly understood. However, the oncogenic role of Notch in HNSCC is likely, as the increased levels of Notch signaling components in OSCC/ESCC were reported 82, 84, 85, although their biological consequences remain to be determined.…”

“…The main concern is regarding the elevated levels of Notch signaling pathway genes in different HNSCC/ESCC. Notch signaling pathway components (including Notch receptors, ligands, or targets genes such as HES1 , HEY1 , or HEY2 ) were found to be amplified or overexpressed in a subset of tongue tumor samples 80, in HNSCC tumors over normal mucosa 81, in OSCC 82, 83, 84, and frequently in ESCC samples 85.…”

The Notch signaling pathway in head and neck squamous cell carcinoma: A meta-analysis

“…1). [16][17][18][19][20][21][22][23][24] An immunohistochemical (IHC) method was used to assess the Notch signaling in HNSCC. These studies were carried out in India, America, Japan, Korea and China.…”

The opposing roles of NOTCH signalling in head and neck cancer: a mini review

“…Further, mRNA levels of several NOTCH pathway genes (NOTCH1, NOTCH2, JAG1, HES1 and HEY1) were shown to be upregulated in oral squamous cell carcinoma (OSCC) compared to normal tongue or oral dysplastic tissues (Hijioka et al , ; Lee et al , ). Similarly, there is evidence to associate NOTCH with tumour progression because elevated protein levels of NOTCH1, HES1 and JAG1 have been reported in oral dysplasias compared to normal mucosa (Zeng et al , ; Yoshida et al , ; Gokulan and Halagowder, ), although it is unclear whether this contributes to the development of malignancy.…”