Anti-apoptotic gene transcription signature of salivary gland neoplasms

We investigated the apoptotic profile of salivary neoplasms in twenty fresh samples of benign and seven samples of malignant salivary neoplasms, using quantitative real time PCR. We further assessed p53 and ki-67 immunopositivity and obtained clinical tumour size data.We demonstrated that BCL-2 mRNA is overexpressed in salivary neoplasms, leading to an overall anti-apoptotic profile. We also found an association between the anti-apoptotic index (BCL-2/BAX) with p53 immunoexpression. A higher proliferative activity was found in the malignant tumours. In addition, tumour size was associated with cell proliferation but not with the transcription of apoptotic genes.In conclusion, we show an anti-apoptotic gene expression profile in salivary neoplasms in association with p53 staining, but independent of cell proliferation and tumour size.Salivary gland tumours have an annual global incidence between 0.4 and 13.5 cases per 100 000 individuals [1]. High proliferative activity, presence of residual tumour and advanced tumour stage were shown to be strong negative predictors of survival in salivary gland neoplasms [2]. Development of targeted therapy calls for a better understanding of their molecular and cellular biology [3].Apoptosis is a highly regulated active process, characterized by cell shrinkage, chromatin condensation and DNA fragmentation promoted by endonucleases. Induction of apoptosis is a normal defense against loss of growth control which follows DNA mutations. Apoptosis is frequently deregulated in human cancers, being a suitable target for anticancer therapy [4].The B-cell lymphoma (BCL-2) family comprises different regulators involved in apoptosis. BCL-2 is an important proto-oncogene located at chromosome 18q21 [5]. It was the first gene implicated in the regulation of apoptosis. Its protein is able to stop programmed cell death (apoptosis) facilitating cell survival independent of promoting cell division [6]. BCL-2 is thought to be involved in resistance