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Expression of glutathione S-transferase pi in human salivary gland and salivary gland tumours

University of British Columbia

The studies of tumour markers, such as enzymatic and genetic markers, are of considerable importance in understanding the mechanisms of tumourigenesis, and in the identification, prevention, and possible treatment of tumours. Glutathione S-transferases (GSTs) are a family of multifunctional enzymes which play important roles in the detoxification of xenobiotics, including carcinogens. Placental GST (GST-π), an acidic form of GST, is normally present in epidermis and oral mucosa where there is constant exposure to xenobiotics. GST-π is markedly increased during neoplastic processes in a number of tissues and is an excellent tumour marker in these tissues. There is a lack of information on the normal distribution of GST-π in human salivary glands and salivary gland neoplasms. This study investigated, immunohistochemically, the normal distribution of GST-π in human major and minor salivary glands and salivary gland neoplasms. The results showed that, in the normal and inflamed salivary glands of all locations (including major and minor salivary glands), the ductal epithelial cells showed moderate to strong GST-π staining, myoepithelial cells showed weak staining, and the acinar cells were negative. The staining was mainly cytoplasmic but small areas of nuclear staining were also noted. The staining pattern of the tumour cells was similar to that of their normal counterparts. The tumour cells were generally positive with GST-π staining except those tumour cells demonstrating acinic differentiation (serous cells in acinic cell carcinoma, mucous cells in mucinous cystadenoma and mucoepidermoid carcinomas). Most of the salivary gland tumours, benign or malignant, showed a weak GST-π staining. Only mucoepidermoid carcinomas demonstrated significantly increased GST-π reactivity compared to other tumours (p<0.001), which may be a reflection of both malignancy and squamous differentiation. The marked increase in GST-π activity in mucoepidermoid carcinomas may be useful in serological screening of recurrent and metastatic mucoepidermoid carcinomas. Pleomorphic adenoma (PA) is characterized by relatively high recurrence rate. The most important reason for the recurrence of PAs is believed to be incomplete first removal of the tumours. It is not clear whether biological behaviour of the tumour cells also contributes to recurrence of this tumour. In the second experiment, GST-π content was compared between non-recurrent PAs and recurrent PAs using a computerized image analysis system. The results showed a significantly higher GST-π content in recurrent PAs when compared to nonrecurrent PAs (p<10⁸). This study has demonstrated that intrinsic cell behaviour (such as increased GST-π content) may play a role in the recurrence of PAs.

Thesis/Dissertation

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2009-01-26

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http://hdl.handle.net/2429/3902

Dental Science

University of British Columbia

UBCV

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