Prognostic evaluation of tumour budding in oral squamous cell carcinoma: Evidenced by CD44 expression as a cancer stem cell marker.

OBJECTIVES: Tumor budding is a sign of invasion and early step for metastasis of many cancers including oral squamous cell carcinoma (OSCC). Evidences suggest the presence of cancer stem cells in tumor buds. CD44 has been reported in tumor growth and metastasis as a cancer stem cell marker in OSCC. The study aims to highlight the prognostic significance of tumor budding in association with CD44 expression as a cancer stem cell marker in OSCC. METHODS: A total of 60 radical neck dissection specimens of OSCC with and without lymph node metastasis were included in the study. The sections were evaluated for TB [Tumor Budding] in H&E and CD44 expression immunohistochemically. OSCC cases were then correlated with clinicopathologic and histomorphologic parameters such as age, gender, habit, site, staging, grading, recurrence, depth of invasion, pattern of invasion, and survival outcomes. Comparison of prognosis and CD44 expression were carried out by statistical methods. RESULTS: A high TB score was significantly correlated with grading (p = 0.037), POI [Pattern of invasion] (0.029), overall survival (p = 0.047). CD44 over expression showed strong correlations with POI (1HPF:p = 0.037;10HPF:p = 0.027), grading (p = 0.037), and overall survival (p = 0.047). Kaplan-Meier analysis revealed overall survival advantage for LTB [Low TB] (85 %) with OSCC compare to HTB [High TB] (75 %) for > 36 months. CONCLUSION: Assessment of TB is effective in predicting prognosis of OSCC. Although CD44 expression has demonstrated strong prognostic influence, there were significant differences in its expression with the parameters.

Prognostic impact of tumor-stroma ratio in oral squamous cell carcinoma - A pilot study.

BACKGROUND: Several prognostic indicators have been used for many decades in an attempt to predict clinical behaviour of Oral Squamous Cell Carcinoma (OSCC). The prognostic value of TSR is yet to be explored in OSCC. Hence, the aim of the present study was to evaluate the prognostic value of TSR in OSCC patients. METHODOLOGY: A cohort of 60 histologically diagnosed cases of OSCC who underwent Radical Neck Dissection was included in the study. TSR was assessed and patients with >50% intratumor stroma were quantified as the stroma-poor group and those with <50% as the stroma-rich group. RESULTS: The parametric tests were performed for the statistical evaluation of TSR with the clinico-pathological variables and the survival. The 3-year overall survival (OS) and disease-free survival (DFS) rates were 95.23% and 69.04%, respectively, in stroma-poor group and 77% and 44%, respectively in the stroma-rich group. CONCLUSION: TSR may serve as a reliable histologic prognostic indicator in OSCC and could be used in routine diagnostic pathology.

MCM-2 expression differentiates potentially malignant verrucous lesions from oral carcinomas.

BACKGROUND: Mcm-2 is a biomarker belonging to Mcm family of proteins which has rarely been used in oral potentially malignant and malignant lesions of the verrucous type. The objective of this study is to assess the expression of Mcm-2 in Normal Oral Mucosa (NM), Verrucous Hyperplasia (VH), Verrucous Carcinoma (VC) and Oral Squamous Cell Carcinoma (OSCC) and compare it with the clinicopathological characteristics. METHODOLOGY: A total of 70 formalin fixed paraffin embedded tissue samples (10 cases of Normal Mucosa NM- Group A, 10 cases of Verrucous Hyperplasia- VH without Dysplasia- Group B, 10 cases of Verrucous Hyperplasia- VH with Dysplasia- Group C, 20 cases of Verrucous Carcinoma VC-Group D, 20 cases of Oral Squamous Cell Carcinoma OSCC- Group E) were subjected to immunohistochemistry with Mcm-2 antibody. Statistical analysis was carried out with various tests like ANOVA, Tukey HSD, Chi-Square and Shapiro-Wilk test by using the SPSS software. RESULTS: There was a significant difference in Mcm-2 expression with quantitative analysis among all the groups (p < 0.05). There was a significant progressive increase in nuclear Labelling Indices (nLI) from NM (49.08%), VC (60.45%), VH with Dysplasia (64.10%), and OSCC (89.22%). CONCLUSION: The findings suggest that Mcm-2 may be a sensitive proliferation marker in oral potentially malignant and malignant lesions which may be useful for differentiating between VH with/ without dysplasia, VC and OSCC.

Immunohistochemical Expression of Cyclin B1 in Epithelial Hyperplasia, Dysplasia and Oral Squamous Cell Carcinomas - A Comparative Study.

INTRODUCTION: Cyclin B1 is important in the cell cycle progression from G2 to M phase. Cyclin B1 binds to CDC2, which then becomes dephosphorylated and gets relocated to the nucleus, ensuring the transition toward mitosis. AIM: Over expression of Cyclin B1, has been reported more recently in breast, colon, prostate, oral and esophageal carcinomas. Thus, the aim of the present study was to examine the expression of Cyclin B1 in hyperplasia, dysplasia and Oral Squamous Cell Carcinomas (OSCC). MATERIALS AND METHODS: A total of 64 histopathologically diagnosed cases of epithelial hyperplasias, dysplastic oral epithelium and OSCC were included in the study. Immunohistochemical procedure was carried out using the monoclonal mouse Cyclin B1 antibody (Clone V-152). The Cyclin B1 positive tumor cells counted were expressed as percentage of positive tumor cells. Nuclear and cytoplasmic labeling index (n&cLI) were calculated. The results were tabulated and statistically analyzed by Kruskal Wallis test- One Way ANOVA and Mann Whitney U- test. RESULTS: Combined n&cLI was considered only in 28.57% of epithelial hyperplasias, 40.7% of oral epithelial dysplasias and 72% of OSCC showed over expression of Cyclin B1 with p value being 0.029. Cyclin B1 expression was not significantly different between the grades of dysplasia, between the grades of OSCC and between the marginal groups. CONCLUSION: The present study demonstrates more than 50% of the study group showing less than 20% of nuclear staining. The importance of such variations within a type of lesion requires further investigation, since Cyclin B1 has proved useful in many studies from esophageal and laryngeal squamous cell carcinoma as a prognostic indicator, an indicator of recurrence and as an indicator for tumor sensitivity to radiotherapy. Further studies are to be extended towards evaluating the role of Cyclin B1 as a prognostic indicator.