Abstract.Oxidative stress results in damage to cellular structures and has been linked to numerous diseases, including cancer. Extracellular superoxide dismutase (Ec-SOd) is a principal enzymatic antioxidant in extracellular space. the purpose of this study was to determine whether the expression of Ec-SOd protein is altered in the carcinogenetic process of oral squamous-cell carcinoma (OScc). immunohistochemical analysis was carried out in matched normal and tumour specimens collected from 58 OSccs and 20 oral premalignant lesions (Opls). correlations between the Ec-SOd expression levels and clinicopathological features of OScc patients were evaluated by Fisher's exact test. although Ec-SOd protein was consistently expressed on the plasma membrane of cells in normal tissues, plasma membranous Ec-SOd expression was lost in almost all the OScc specimens examined (98%). instead, positive Ec-SOd expression was detected in the cytoplasmic compartments of cancerous cells in both Opls (65%) and OSccs (52%), together with a high incidence of lymph node metastasis (p=0.0397). these results suggest that the dysregulation of Ec-SOd protein expression is a frequently occuring and early event in oral carcinogenesis, and that cytoplasmic Ec-SOd may contribute to the increased aggressiveness of OScc.
IntroductionOral squamous-cell carcinoma (OScc) is a major cause of morbidity and mortality worldwide, accounting for 275,000 new cases and more than 120,000 deaths annually (1). despite therapeutic and diagnostic advances, patients are often diagnosed at advanced stages, and mortality rates are still increasing (2). this highlights the need for continued efforts to discover suitable biomarkers for early disease diagnosis and for the improved understanding of disease pathogenesis as a first step towards improving treatment. Considering these issues, it is imperative to study OScc at the genetic level and to characterize the genetic changes responsible for carcinogenesis and tumour behavior.Since cancer has the specific potential of rapid and unlimited growth, oxidative stress, which is characterized by an imbalance between the presence of relatively high levels of toxic reactive species principally consisting of reactive oxygen species (rOS) and antioxidative defense mechanisms, is a common feature in a wide range of solid tumors, including OScc (3,4). Some studies have found that cells undergoing neoplastic transformation show marked changes in metabolism, resulting in an increase in oxidative stress in cancerous cells (5,6). Enhanced oxidizing status in transforming cells is thought to induce dna damage, leading to genetic lesions that initiate tumorigenicity and facilitate immortalization, enhance cell proliferation and sustain subsequent local and systemic tumor progression (7-9). additionally, recent studies revealed that oxidative stress is not merely toxic due to rOS production by metabolism, but also serves an important regulatory role in numerous oncogenic signaling pathways in cancerous cells (10,11).Superoxide dismutas...