Expression of p53 tumor suppressor gene in adenoid cystic and mucoepidermoid carcinomas of the salivary glands

Abstract

Seventeen adenoid cystic carcinomas (ACCs) and 27 mucoepidermoid carcinomas (MECs) occurring in the salivary glands were analyzed for p53 tumor suppressor gene alteration (exons 5–8) and protein expression. The cell proliferation activity was also examined by Ki-67 immunohistochemistry. The p53 alterations were detected in three samples (17.6%) of ACC and in four samples (14.8%) of MEC, and were only found in carcinomas arising in the minor salivary glands. The occurrence of the p53 gene alteration is less frequent in ACC and MEC than that in other kinds of tumors, and therefore does not seem to play a critical role in the course of the tumorigenesis in ACC and MEC. All ACC samples arising from the minor salivary glands exhibiting p53 gene alterations showed recurrence/metastasis, thus suggesting a poor outcome of these patients. All ACCs and three out of four MECs samples with p53 gene alterations showed the lowest degree of p53 immunostaining ratio, thus suggesting that no correlation exists between the p53 gene alterations and the p53 immunostaining in these salivary gland carcinomas. No significant relationship was demonstrated between the immunostaining ratio of either p53 or Ki-67 and the morphological growth pattern or patient clinical course in the ACC samples. The p53 immunopositivity in MEC correlated to the histological grade. The Ki-67 immunostaining ratio was also significantly related to the histological grade and the clinical course in MEC.

Introduction

Adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma (MEC) are common malignant tumors in the major and minor salivary glands. ACC is considered to have aggressive biological characteristics such as local recurrences, perineural spread and late distant metastasis. However, various histological features such as perineural and perivascular spread, mitotic activity and pleomorphism appear to have no exact correlation to the prognosis of patients with ACC [1]. The relationship between various histological parameters and the biological potential of MEC also remains controversial [2]. As a result, no unequivocal uniform system has been yet established to predict the outcome of patients with ACC and MEC. Auclair et al. proposed a reliable grading system for MEC in predicting the clinical course [3]. An extensive study of Goode et al. indicated that the value of grading system for mucoepidermoid carcinoma in the major salivary glands depended on the site of the salivary glands from where the MEC occurred, and consequently they concluded that immunohistochemical markers such as p53, Ki-67 and proliferating cell nuclear antigen may potentially be able to predict the tumor behavior [4].

An alteration or allelic loss of the p53 tumor suppressor gene is often observed in a variety of human cancers, and is considered to play a critical role in the transition to malignant growth. However, there have been few reports on p53 gene analyses in salivary gland carcinomas [5], [6], [7], and therefore the effects of p53 gene alterations on the biological behavior of ACC and MEC still remain unclear. In the present study, we examined the p53 alterations in exons 5–8 (hot-spot) using polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) and plasmid sequence. The immunohistochemical expressions of p53 and Ki-67 proteins were also examined. Furthermore, relationships between these data and either the growth pattern/tumor grade based on either histological features or the patient clinical course were investigated.