Molecular profiling of oral squamous cell carcinoma associated with oral submucous fibrosis.

Context: Areca nut, a causative factor for oral submucous fibrosis (OSMF), is identified as a Group 1 human carcinogen. Oral squamous cell carcinoma (OSCC) associated with OSMF is now one of the most common malignancies in South and Southeast Asian countries. Aim: The present study was aimed to have clarity whether OSCC associated with OSMF is a pathologically different disease having different prognosis. Settings and Design: The difference between OSCC associated with OSMF and OSCC not associated with OSMF was studied in relation to expression of molecular markers, Ki-67, a proliferative and prognostic marker for OSCC and matrixmetalloproteinase-9 (MMP-9), and alpha smooth muscle actin (α-SMA), markers for invasiveness. Subjects and Methods: Expression was analyzed immunohistochemically using paraffin-embedded tissues from ten normal oral mucosa (Group I), thirty OSCC associated with OSMF (Group II), and thirty OSCC not associated with OSMF (Group III). Results: Group II showed OSCC occurring at younger age with more cases of well-differentiated OSCC. It also showed lower expression of Ki-67, MMP-9, and α-SMA as compared to Group III, and the difference was statistically significant. In addition, statistically significant low expression of markers was found in well and moderate grades of Group II as compared to those of Group III. Conclusion: OSCC associated with OSMF may have better prognosis and survival rate as it is found to occur at younger age with better grade of tumor differentiation and less expression of molecular markers Ki-67, MMP-9 and α-SMA. Thus, OSCC associated with OSMF can be considered a different disease pathologically and biologically. In-depth analysis of this molecular profiling can help to establish diagnostic, prognostic and therapeutic modalities for this unique malignancy.

Cancer Stem Cell Markers, CD44 and ALDH1, for Assessment of Cancer Risk in OPMDs and Lymph Node Metastasis in Oral Squamous Cell Carcinoma.

Tumour heterogeneity in oral cancer is attributed to the presence of cancer stem cells (CSCs). CSCs are the most migratory and metastatic cellular subpopulation within tumours. Assessment of CSC markers as significant predictors of lymph node metastasis may prove valuable in the clinical setting. Furthermore, analysis of this panel of putative stem cell markers in oral dysplasia may additionally inform of the likelihood for oral potentially malignant disorders (OPMDs) to progress to oral squamous cell carcinoma (OSCC). The present study aims to assess the significance of CSC markers in the progression of OPMDs to OSCC and assessment of lymph node metastasis in OSCC. CD44 and ALDH1 were assessed immunohistochemically in 25 normal, 30 OPMDs, and 24 OSCCs. CD44 is a membranous marker and ALDH1 is a cytoplasmic marker. The immunohistochemical expression of these markers were compared between OPMDs with and without dysplasia, as well as between low-risk and high-risk dysplasias. Similarly, expression was compared between OSCC with and without lymph node metastasis and among grades of OSCC. Positive CD44 expression was seen in all normal mucosal tissues. The expression decreased from normal epithelium to OPMDs but increased in OSCC. CD44 expression was positive in 21 cases of OSCC (87.5%) and reduced from well-differentiated to poorly differentiated OSCC. CD44 staining index was higher in OSCC without lymph node metastasis (3.59) when compared with OSCC with lymph node metastasis (1.33). There was a statistically significant difference observed in the ALDH1 staining index among three groups (p < 0.05), with highest expression seen in OSCC. Within OPMDs, the ALDH1 staining index was statistically higher in OPMDs with dysplasia as compared to OPMDs without dysplasia. Furthermore, the expression was higher in OPMDs with high-risk dysplasia when compared with low-risk dysplasia, but this was not statistically significant (p = 0.82). In conclusion, The CD44 positive population possesses properties of CSCs in head and neck carcinoma, and continuous shedding could be found after CD44 down-regulation. The present study reports differences in ALDH1 expression between OPMDs with and without dysplasia, dysplastic and non-dysplastic epithelia, and low-risk and high-risk dysplasia. These findings may suggest ALDH1 as a specific marker for dysplasia. CD44 demonstrated a difference in staining index in OSCC without lymph node metastasis versus OSCC with lymph node metastasis. These findings may suggest CD44 as a marker for lymph node metastasis. Both proteins may play key roles in the tumorigenicity of CSCs in OPMDs and OSCC.