Oda T et al. proposed three mechanisms of alteration of cadherin-mediated cell adhesion system in human cancers in vivo and in vitro. The first is down-regulation of E-cadherin expression and its gene mutation
. Existence of altered E-cadherin expression in human cancers and a significant relationship between reduced E-cadherin expression and clinicopathological factors, such as dedifferentiation, invasiveness, or metastasis was previously reported
. The second is abnormality or deletion of catenins
[13, 14]. The third abnormality is biochemical modification of catenins. It has been demonstrated that tyrosine phosphorylation of β-catenin induced by various factors (eg. v-src, hepatocyte growth factor and epidermal growth factor) suppresses E-cadherin function in vitro
The present study revealed the down regulation of molecular markers β-catenin and E-cadherin in OSCC along with aberrant expression of vimentin. However, the present study did not show any significant difference in the expression of E- cadherin, β- catenin and vimentin in OSCC with and without lymph node metastases.
As proposed by various studies
[16–19], there was decreased expression of E-cadherin and β-catenin in OSCC tumour cells, in comparison to strong expression in the control groups. This was statistically significant in OSCC without lymph node metastasis (p = 0.002, p = 0.011) and OSCC with lymph node metastases (p = 0.011, p = 0.024).
Epithelial-mesenchymal transition is an important biological process during development and oncogenesis. It is characterized by a reduction of epithelial polarities and production of mesenchymal phenotypes. Down regulation of epithelial marker like E-cadherin and increase in mesenchymal marker vimentin are hallmarks of transition
Few studies have detected the expression of vimentin in OSCC patients and cell lines
[22, 23]. Similar feature was noted in the present study.
Down regulation and loss of E-cadherin was associated with lymph node metastases and advanced stage of OSCC according to various studies
[18, 24–26] while few studies
[16, 17, 27, 28] failed to prove this prognostic value. The present study followed the latter trend.
Reduced staining intensity of the E-cadherin molecule has been correlated by Rodrigo et al. with the presence of nodal metastatic disease in a study on 101 patients with supraglottic laryngeal carcinoma
 although, few studies failed to show this relationship
[27, 30]. Bukholm et al.
 reported that there was no significant difference between the expression of E-cadherin and the presence of regional metastasis in human breast cancer, and it is said that the significance of changes in the E-cadherin complex may vary from tumour to tumour
Reduced β-catenin staining was a predictive marker for lymph node metastases in OSCC according to few studies
[24, 33, 34] and not by others
[16, 27, 35]. The present study did not have a significant difference in the reduced expression of β-catenin and lymph node metastases in OSCC.
Several factors related to methodology may account for the discrepancy in results. The method of evaluation of immunostaining and the definition of under-expression is quite variable, hence compromising accurate comparison of data.
In some studies, a semi-quantitative estimation of the immunoreactive intensity was used
[24, 25, 33, 36, 37] with varying percentage criteria, while other studies have not assessed expression according to the percentage of positively stained cells
[38, 39]. Moreover, the expression analysis has been carried out in different areas of the tumour by different investigators. Some studies have focussed on the invasive tumour front
[33, 38] while other studies have examined expression in random areas
[24, 36, 37, 39] within the tumour. It would, however, appear from the results in the present study and other studies on OSCC
[16, 17, 25, 27, 28, 35, 36, 39] that E-cadherin and β-catenin are probably not the key determinants for regional metastases in OSCC.
In this study, all tumors in both the groups expressed cytoplasmic positivity for vimentin with varying intensity. Of 60 cases of OSCC, 45 cases (75%) exhibited a low immunoreactive score and 15 cases (25%) exhibited high immunoreactive score. Poorly differentiated OSCC constituted two cases, of which one exhibited high immunoreactive score (50%). The number of cases in the poorly differentiated carcinoma category was less for a valid comparison.
Various molecules have been studied in head and neck carcinomas. Low level of p27 expression has been reported an unfavorable prognostic factor for patients with nasopharyngeal carcinoma
. CypA/MMP9 signal pathway and up-regulation of USP9X may be attributed to the malignant transformation of esophageal squamous cell carcinoma (ESCC)
[41, 42]. Also, over-expression of ABCG2 and V-ATPase is noted in ESCC. RNAi targeting CXCR4 is known to inhibit proliferation and invasion of esophageal carcinoma cells
. Both ABCG2 and V-ATPase are over-expressed in esophageal squamous cancer cells
. Some new molecules are being studied in head and neck squamous cell carcinomas (HNSCC). Mir-205 has been demonstrated as a novel molecular marker for the detection of metastatic HNSCC
. In another study, primary tumors and positive nodes of the metastatic cases revealed decreased expression of collagen XVIII and CBP2/HSP47 in metastases
. More studies on role of integrins, epidermal growth factor receptor, matrix metalloproteinases, cathepsins, chemokine receptors and angiogenesis markers are needed for future.