Cytokeratin profile in mucoepidermoid carcinoma is not related to its histological grading of malignancy

Abstract

The objective of this experiment was to determine the relationship between the expression of cytokeratins (CKs) and histologic grading in MEC. Eleven cases of MEC were selected and graded as low, intermediate and high-grade tumors. The expression of CKs 7, 8, 10, 13 and 14 was assessed immunohistochemically using streptavidin–biotin complex method. The results showed that the studied CKs were expressed in most cases of MEC, independently of histologic grading. Nonetheless, low-grade tumors demonstrated intense staining of CK 7 and 8; additionally, CK 10 and 13 were more pronounced in this grade. The immunoexpression was variable according to cellular type and organization pattern of the tumor. Mucous cells were positive for CK 7 and 8; epidermoid cells were stained for CK 10, 13 and 14; CK 7, 8, 10 and 14 were observed in intermediate cells, and CK 7 was occasionally seen in clear cells. Cystic structures and duct-like elements in MEC were positive for CK 7 and 8, whereas solid nests showed positivity for all CKs. These results suggest that expression profile of these proteins does not reflect the biological behavior of MCE, however, it guides the detection of cellular types and differential diagnosis from other salivary gland tumors.

Introduction

Mucoepidermoid carcinoma (MEC) is the most common malignant tumor of all carcinomas developing in the major and minor salivary glands (Ostman et al., 1997, Figueiredo et al., 2001, Kokemuller et al., 2005). This neoplasm was first recognized by Masson and Berger in 1924 (Prgoment et al., 2003). Since its first description, several studies have attempted to identify the MEC well-known variable biological behavior. This neoplasm can be highly aggressive; however, it shows sometimes a slow growth resembling a benign lesion.

Some factors can be related to biological behavior and patient's outcome in MEC such as anatomical site, clinical stage, invasion of adjacent structures, presence of distant metastasis (Good et al., 1998, Pires et al., 2004, Kokemuller et al., 2005) and histologic grading of malignancy (Guzzo et al., 2002, Spight and Barret, 2002, Perez-Ordonez, 2003).

Histologically, MEC is composed of variable cell types including mucous, epidermoid and intermediate cells that can be arranged in solid nests or cystic structures (Dardick, 1996). Not only the proportion and organization of these cells but also the degree of atypia and number of mitosis serve as criteria for histologic grading (low, intermediate and high grade), which is correlated with poor or good clinical outcome of this tumor (Ellis and Auclair, 1996).

The great structural and cellular diversity of MEC is responsible for intense discussion concerning its histogenesis. The role of several immunohistochemical markers has been studied in order to reach a better understanding about the factors related to histogenesis and prognosis in MEC.

Cytokeratins (CKs) constitute the major component of the cytoskeleton of all epithelia; the use of these intermediate filaments in pathology has been assessed in the diagnosis of undifferentiated neoplasms and determination of tumoral subtype (Chu and Weiss, 2000, Upsani et al., 2004). Indeed, there has been demonstrated an association between CKs expression with biological behavior and tumor differentiation in oral squamous cell carcinoma. Moreover, the study of these proteins has clarified relevant aspects regarding the histogenesis of several salivary gland tumors.

Few studies have been carried out to verify CKs profile in MEC and the relationship with its differentiation. Thus, the goal of the present experiment was to investigate CKs expression and the relation with histologic grading in MEC in order to provide data for a better understanding of tumor biological behavior. Furthermore, aspects related to MEC histogenesis were analyzed by comparing CKs pattern in normal salivary gland adjacent to the tumor.