Malignant salivary gland tumors and cyclo-oxygenase-2: a histopathological and immunohistochemical analysis with implications on histogenesis

The classification system for malignant salivary gland tumors (MST) is largely dependent on its histogenesis. The histogenesis is uncertain but the "bicellular theory of origin" has been accepted by most and states that malignant transformation of reserve cells from either the intercalated or excretory duct are responsible for the development of MST. Cyclooxygenase-2 (cox-2), a potential molecular marker for MST, was analyzed on a series (n=56) of MST with the aim of determining the morphological MST subtypes capable of cox-2 overexpression and correlating its expression with histogenesis. Fifty six primary major and minor gland MST were stained with anti-cox-2 antibody and rated with a combined score that added a scale of intensity to the percentage of tumor cells that overexpressed the cox-2 protein. A score of <3: negligible or negative staining; score of 4-5; moderate staining; score of 6-7; strong staining. Tumor types were segregated by morphology, histological features and proposed histogenesis. Strong cox-2 overexpression was noted in all MST of proposed excretory duct origin: salivary duct carcinoma (100%), mucoepidermoid carcinoma (MEC) (92%), and adenocarcinoma nos (AdC nos) (83%). Primary squamous cell carcinoma (PSCC) was the exception. Negative expression was noted in all tumors of proposed intercalated duct origin (adenoid cystic carcinoma, basal cell adenocarcinoma and acinic cell carcinoma) with the exception of one case of polymorphous low grade adenocarcinoma. Strong cox-2 overexpression was noted in the epidermoid cells of MEC, abluminal duct cells surrounding the duct-like structures and ductal cells of AdC nos and salivary duct carcinoma. Myoepithelial and acinar cells were unreactive. Although preliminary, the results of our study support the concept that MST of proposed excretory duct origin share a common histogenesis. Negligible cox-2 expression in PSCC may provide a useful tool for diagnosing the often histologically indistinguishable cases of high grade MEC. Follow-up studies on a larger series of MST are warranted.