Correlation of c‐erbB‐2 and S‐100 expression with the malignancy grading and anatomical site in oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is the most common malignant tumour occurring in the oral cavity. In the majority of the cases, it is diagnosed at an advanced stage, and as a direct consequence, it may present with a poor prognosis (Schutz 1997). Several researchers have showed that the inferior lip, the edge of the tongue, the mouth floor and the soft palate are the most common anatomical sites where this disease arises (Souza & Pereira Pinto 1981; Pereira 1982; Costa et al. 1999b). Despite recent improvements in the diagnosis and treatment of cancer, there are still many difficulties in evaluating the prognosis of the carcinomas of the oral mucosa. Thus, an attempt to find more significant information to predict the biological behaviour of this neoplasm and to look at the possible relationship between the tumoural progression and the products of genes which regulate cell proliferation and differentiation, such as the proto-oncogenes, anti-oncogenes and apoptosis-regulating genes, has recently been reported (Novellino 1998; Costa et al. 1999a). The c-erbB-2 proto-oncogene (HER/NEU/neu) encodes a 185 transmembrane protein product of tyrosine kinase family, with extensive homology to the epidermal growth factor receptor, which has been mapped to the 21 region of chromosome 17 (Schechler et al. 1985). The amplification of the c-erbB-2 gene has been demonstrated in many carcinomas of glandular origin, and its immunohistochemical expression has been proved to be closely associated with its amplification level (Sugano et al. 1992). The amplification and, consequently, the overexpression of the c-erbB-2 gene, as well as its relationship with tumorigenesis, was first reported by Schechler et al. (1985) in neuroglioblastomas of rats. Since then, the overexpression of this oncoprotein has been detected in many human malignant neoplasms. In addition, Shrestha et al. (1992) asserted that it is possible to establish a positive correlation between the overexpression of c-erbB-2 gene with poor tumour prognosis. In clinical settings, the role of aberrant c-erbB-2 expression is well documented in breast and ovarian cancer, but the results are still inconclusive in other tumours. Increased c-erbB-2 oncoprotein levels have been demonstrated in squamous cell carcinoma of the oral cavity (O–charoenrat et al. 2002). Langerhans' cells (LCs) are cells with dendritic morphology located in the squamous epithelia of the epidermis and mucosa, first reported by Paul Langerhans in 1868 (Lombardi et al. 1993; Jacobs et al. 2001). LCs are currently considered as important modulators of immune response against antigens found within the epithelial tissue due to their ability in presenting antigens to CD4+ T cells. Thus, these dendritic cells are able to induce an adaptive immune response of both cellular and humoral type (McLellan & Kampgen 2000). McLellan & Kampgen (2000) reported a significant decrease in LC populations after antigen presentation to CD4+ T cells (T-helper lymphocytes). These researchers allege that this phenomenon is apparently mediated by an apoptosis-induction process. Moreover, it has also been reported that the number of LCs within the epithelial tissue is largely variable, increasing or decreasing, according to the changes in mucosal or dermal homeostasis (Babi 1998). Therefore, it has been suggested that LCs, due to their immunological properties, might play an important role in the anti-tumour resistance against malignant tumours rising from the lining epithelium of dermis and mucosa. Consisted with this, Pinto–Junior et al. (1994) reported that analysis of LC expression in association with the tumoural component can be useful in evaluating the immunological status of the patient. Research by Arany et al. (1998) indicated that a decrease in the number of LCs was associated with poorly differentiated OSCC. The opposite was seen in moderately differentiated and well-differentiated tumours. The authors ascribed this phenomenon to a possible immune suppression induced by anaplastic tumour cells. Protein S-100 is used to identify LCs. This protein was first isolated from the bovine brain and then was identified in glial and Schwann cells of the nervous system, as well as in epidermal LCs, myoepithelial cells of the salivary and mammary glands and in many other cells of various organs (Turusov 1990). Even though S-100 protein is not a specific marker of LCs, the peculiar dendritic morphology and the localization can be quite helpful in distinguishing this cell population from other S-100-positive cells (Johnson et al. 2000). As there have been only few reports looking at the role of both c-erbB-2 gene product and LC population in the pathogenesis of OSCC, the goal of this study was to investigate the relationship among the overexpression of c-erbB-2 oncoprotein, the histological grading and the anatomical site of occurrence of this lesion. In addition, the LC expression pattern and its relationship with the previously mentioned variables was also investigated.