Staging of salivary gland neoplasms: role of histopathologic and molecular factors.

Cancer is a disease of altered cellular genes. These altered genes, in turn, produce the malignant phenotype by inducing changes in proliferation and differentiation during the cell cycle. The changes can be assessed by techniques to measure proliferation and by histologic grading to distinguish levels of differentiation. Since proliferation factors and differentiation end points reflect the net effect of genetic damage and include, therefore, the accumulated changes in genes, they more aptly qualify as potential prognostic indicators than do individual oncogene alterations. By using mucoepidermoid carcinoma of the major salivary glands as the test model, I strongly suggest that a reproducible (three-tiered) grading system and measurements of proliferation (nuclear markers: proliferating cell nuclear antigen and, possibly, Ki-67; and proliferation fraction as determined by flow cytometry) can serve as cellular/molecular factors worthy of inclusion in existing clinical staging systems of salivary gland neoplasms.