Integrin receptors and their relationship to cellular proliferation and differentiation of oral squamous cell carcinoma. A quantitative immunohistochemical study

Abstract

The expression of extracellular matrix (ECM) proteins (fibronectin, laminin, collagen IV) and ECM receptors of integrin type (alpha 2 beta 1, collagen receptor; alpha 6 chain of the fibronectin receptor; alpha 6 chain of the laminin receptor) were examined in normal oral squamous epithelium and in invasive areas of squamous cell carcinomas with various differentiation and proliferation activities (Ki-67 antigen labelling), evaluating the presence, quantity (using an image analysis system) and distribution of the integrin subunits. In the mucosa, there was uniform immunostaining for alpha 2 beta 1 and alpha 6 concentrated at the cell membrane in the basal/supra basal cell zone, whereas, alpha 5 showed a discontinuous staining of the basal cell-basement membrane interface. alpha 2 and alpha 6 could be visualized in all carcinomas. alpha 5 showed low expression preferentially in less differentiated carcinomas. In contrast to normal mucosa, there was an increase in alpha 6 staining in well-differentiated carcinomas. Dedifferentiation of oral carcinomas was accompanied by an increase in cellular proliferation and with a decrease in alpha 2 beta 1 and alpha 6 staining. This reduction of alpha 6 staining was shown to be statistically significant, suggesting that this integrin may be a valuable grading parameter for oral squamous cell carcinoma.

Immunohistochemical profile of integrins in enlarged dental follicles and dentigerous cysts

“…These cells are characterized by well-established differentiation, a fact explaining the high expression of ␣ 5 ␤ 1 integrin. However, these results disagree with the findings of Kosmehl et al, 18 who observed discontinuous staining for ␣ 5 ␤ 1 integrin at the epithelial-basement membrane interface in normal oral mucosa and a more intense staining in poorly differentiated epidermoid carcinoma. According to these authors, expression of ␣ 5 ␤ 1 integrin tended to be higher in more undifferentiated cells.…”

Distribution of laminin and fibronectin isoforms in oral mucosa and oral squamous cell carcinoma

“…In dysplasia and carcinoma BM structural irregularities, including reduplication, splitting, attenuation and breaks (Ueno et al, 1997) have been well documented by electron microscopy. Moreover, immunohistochemical BM defects and a loss of corresponding integrins in head and neck squamous cell carcinomas have been reported (Downer et al, 1993;Harada et al, 1994;Kobayashi et al, 1995;Kosmehl et al, 1995aKosmehl et al, , 1996. In this study, multifocal breaks of BM continuity were observed in the invasion zone of all carcinomas, regardless of the laminin chain specificity of the antibodies.…”

Expression of Integrins in Squamous Cell Carcinoma of the Oral Cavity: Correlations with Tumor Invasion and Metastasis

“…The integrins also reflect the differentiation status of tumor cells [31][32][33] and are considered to be involved in the interaction of tumor cells with ECMs. 34 Immunohistochemical staining for specific cytokeratins has been used to categorize OSCC in accordance with differentiation status.…”