Background and objectives: Laminin is a significant basement membrane (BM) glycoprotein, the expression of
which reflects BM integrity more precisely than do other ECM proteins. The present study aimed to evaluate laminin
expression in oral squamous cell carcinomas OSCC and to determine any associations with clinico-pathological
parameters (surgical margin status, lymph node involvement, survival and recurrence). Methods: Laminin expression was
evaluated in 31 cases of biopsy-proven OSCC by immunohistochemical staining and its association with prognosticators
and the Brynes grading system was determined by appropriate statistical analysis. Results: We observed a significant
increase in linear staining pattern (p<0.001) at the tumour-host interface in well-differentiated OSCC cases, in contrast
to poorly differentiated lesions which exhibited intense cytoplasmic expression within tumour cells. Higher cytoplasmic
laminin expression was seen in 33.3% of cases with involved surgical margins and 69.2% of cases with lymph node
metastasis (along with weak/absent staining of laminin around the tumour-host interface – Basement membrane around
tumour islands). Similarly, in 60% of the cases who died and in 81.8% of cases with tumour recurrence, moderately
intense cytoplasmic laminin expression was seen within tumour cells. On comparing variables of the Brynes grading
system, significant cytoplasmic expression of laminin was linked with mild inflammation (p<0.0016) and increased
mitotic activity (p<0.008). Conclusion: Based on these observations, immunohistochemical expression of laminin
might be useful to evaluate histological differentiation and aggressiveness of OSCCs.

http://journal.waocp.org/article_57579_4b578c3ce836c8b56ac5a1a0d98919c4.pdf

Expression of Laminin in Oral Squamous Cell Carcinomas

Background and Objectives: In India, oral submucous fibrosis (OSF) is a commonly encountered precancerous disorder. It is a disease with a protracted course and characteristic clinical features caused by the habit of consuming areca nut. Histologically, the main pathology is extensive fibrosis of the mucosa. OSF can be categorized into four grades based on histology. Inflammatory cells and keratocytes are stimulated by the areca nut alkaloids, and they release transforming growth factor-beta (TGF-β). It has been advocated to play a major role in OSF pathogenesis by increasing collagen synthesis and preventing collagen degradation. Mast cells (MCs) are the additional key players in the pathogenesis of OSF. There is confusion regarding the functional relationship of MC with TGF-β. Few studies have shown TGF-β can repress MC function, whereas other studies have established that TGF-β is a chemotaxin for MCs. However, there is dearth in literature regarding their interaction in OSF. Hence, this study attempted to show a relationship between TGF-β and MC in different grades of the disease, so as to further explicate the pathogenesis of OSF. Materials and Methods: A total of 48 OSF cases were stained using TGF-β antibody. Its staining intensity and staining area were calculated. Sections from same blocks were also stain MCs using 1% toluidine blue. The number of MCs was counted for all the cases. Expression of TGF-β was correlated with MC count in all OSF grades. Results: On correlating TGF-β and MC between the histologic grades, there was a strong negative correlation for Grade I, moderately positive for Grade II and no correlation for Grade III OSF. Interpretation and Conclusions: Among the different grades of OSF, the correlation between MC and TGF-β varies, depending on the severity of inflammation, and the concentration of TGF-β and further investigation in this field may elucidate their role in determining the severity of OSF.

Correlation between transforming growth factor-beta expression and mast cell count in different grades of oral submucous fibrosis

Assessment of syndecan-1 antigen in oral submucous fibrosis according to grades of epithelial dysplasia

Introduction: CD44 is a cell surface adhesion glycoprotein found in various cells. The present study aimed to evaluate the immunohistochemical expression of CD44 in the erosive lichen planus (ELP), epithelial dysplasia (ED), and oral squamous cell carcinoma (OSCC) to compare the expression in a possible premalignant lesion, a definite premalignant lesion, and a malignancy. Materials and Methods: In this descriptive-analytical study, immunohistochemical staining was performed on 10 ELP cases (without dysplasia), five ED cases, and 20 OSCC cases using the standard Envision technique. In addition, the extent and intensity of CD44 staining and thickness of the stained epithelium were assessed. Data analysis was performed in SPSS using Kruskal-Wallis test. Results: 60 of OSCC samples had moderate membranous and cytoplasmic staining, in which more than two-thirds of the epithelium was stained. Moreover, moderate to severe, and mostly membranous immunostaining were observed in all ELP cases, while two-thirds of the epithelium showed immunostaining in all the samples. In the ED samples, staining intensity was reduced in more severe cases, and the staining pattern changed from membranous to cytoplasmic and membranous. Furthermore, in 80 of the ED cases, two-thirds of the epithelium was stained. Comparison of the immunostaining in ELP, ED, and OSCC samples indicated no significant differences between these lesions Conclusion: According to the results, CD44 expression in ELP, ED, and OSCC had no statistically significant difference. Therefore, this protein might not be an appropriate marker to confirm the premalignancy of ELP or predict the invasion in OSCC and premalignant lesions.

Immunohistochemical Expression of CD44 in Erosive Lichen Planus, Epithelial Dysplasia, and Oral Squamous Cell Carcinoma

Oral leukoplakia (OL) and oral submucosal fibrosis (OSMF) are precancerous conditions with common etiologies but with different risks for oral cancer (OC) progression. In rare cases, both conditions occur in the same patient and provide an opportunity for understanding the common and distinctive variants upon exposure of genetically identical normal cells to the same carcinogen(s). We performed exome sequencing of a patient with OL (hyperplasia, but no dysplasia) and OSMF (grade II) in the opposite cheeks using blood DNA as the reference genome. The overall somatic variant burden was higher in OSMF than OL, but opposite in the case of copy number alterations. OL-specific variants were enriched in genes associated with DNA repair, cell division/cell cycle checkpoint pathways, whereas in OSMF, extracellular matrix-receptor interaction was mainly affected. The proportions of variants in cancer driver genes and cancer driver mutations were similar in both cases indicating no difference in the potential risk associated with the two conditions at the stages sampled. Future studies on rare cases similar to the one described in this report will help in understanding the molecular basis of differences associated with OL and OSMF and shared processes accompanying OC progression.

Comparative Somatic Variant Analysis of a Rare Case with Concurrent Oral Leukoplakia and Oral Submucosal Fibrosis

Background: Syndecan‑1 is abundant in normal tissues and reduced in squamous cell carcinomas. Leukoplakia and oral submucous fibrosis (OSF) are oral pre‑cancerous disorders that have potential for malignant transformation. The aim of this study was to evaluate the expression of syndecan‑1 in leukoplakia and OSF and to identify its role as a reliable marker for predicting malignant changes. Materials and Methods: Expression of syndecan‑1 was examined immunohistochemically in 42 cases of oral leukoplakia with or without epithelial dysplasia, 28 cases of OSF and 10 cases of normal oral epithelia as control. Mann-Whiteny ‘ U ’ test was used for statistical analysis and the level of significance was fixed at P < 0.05. Results: Intense syndecan‑1 expression was observed in nine cases with normal epithelium. Immunopositivity was lost gradually as the extent of epithelial dysplasia increased. The significant reduction in syndecan‑1 expression was observed in leukoplakia as epithelial dysplasia progressed from moderate or severe. Similarly, significant reduction was observed in staining intensities in OSF with dysplasia. Conclusion: The results reveal that down‑regulation of syndecan‑1 expression is associated with dysplastic changes in leukoplakia and OSF. Thus syndecan‑1 can be considered as marker for predicting malignant changes. Key Words: Immunohistochemistry, leukoplakia, oral submucous fibrosis, syndecan‑1

Immunohistochemical analysis of syndecan‑1 in leukoplakia and oral submucous fibrosis

AIM To evaluate the expression of laminin in various grades of oral squamous cell carcinoma (OSCC) in order to determine whether this protein can be used as a marker for early detection and elucidation of oral cancer. MATERIALS AND METHODS Immunohistochemical staining for laminin was done on 60 selected archival blocks of histopathologically diagnosed cases of primary OSCC and the laminin expression was compared between the different histopathological grades of primary OSCC. The statistical analysis was performed by using Chi-square (X square) test and Gaussiantest with a probability of p > 0.05 was considered as significant. RESULTS It was observed that laminin expression decreased with tumor progression which may be correlated to the tumor aggressiveness. CONCLUSION There was a gradual decrease of laminin staining with decreasing cellular differentiation, with differentiated lesions showing a more conspicuous staining of basement membrane glycoprotein than less differentiated lesions. CLINICAL SIGNIFICANCE An understanding of how the extracellular matrix influences tumor development and invasion is fundamental in the development of new prognostic indicators and treatment strategies for oral squamous cell carcinoma..

/pdf/expression-of-extracellular-matrix-laminin-in-oral-squamous-1bwjp3htys.pdf

Sushant S. Kamat

Papers

Immunohistochemical analysis of syndecan‑1 in leukoplakia and oral submucous fibrosis

Expression of extracellular matrix-laminin in oral squamous cell carcinoma: an immunohistochemical study.