Abstract

Navneet Saini61093*, Rashmi Babbar61094 and Ashish Kumar Mandal61095

Introduction: Caspase a family of cysteine protease plays an important role in programmed cell death. Caspase-3 and Caspase-8 are key regulators of apoptosis. Caspase-8 plays principal role in conveying signals from death ligand receptors to intracellular pro-apoptotic machinery. It was found exclusively in the cytoplasm, however, its presence has also been observed in other intracellular compartments. The role of Caspase-8 in tumor progression is contentious.

Caspase-3 is a chief mediator of apoptosis and is cleaved to create an active form. The precursor form of Caspase-3 is localized in cytoplasm while active form is translocated to nucleus. Expression of active form of Cassspase-3 is studied in various forms of carcinomas but few reports regarding pro-caspase-3 are available. Some studies have also report the presence of inactive Caspase-3 in the nucleus.

Since caspases are located in different cellular compartments their deregulations might be responsible for the development of malignancies. We aimed to study the expression of pro-caspase-3 and caspase-8 in the various intercellular compartments of tumor area, adjacent normal and dysplastic area in multi-step carcinogenesis of oro-pharyngeal carcinoma.

Materials and methods: The research study was undertaken in Maulana Azad Medical College New-Delhi. Clinically diagnosed one hundred and fifty cases of squamous cell carcinoma of oro-pharyngeal region and one hundred and twenty eight control subjects were studied. Caspase-8 and pro-caspase-3 proteins were studied in tumor area and adjacent normal-dysplasia, by immunostaining based on avidin-biotin peroxides complex technique.

Results: The Caspase-8 cytoplasm expression was compared to adjacent normal and dysplasia group, significant increase in caspase-8 cytoplasm expression in tumor group was seen (P<0.001). Similar results were also observed in nuclear caspase-8 (P=0.0001). The cytoplasm pro-caspase-3 expression in tumor higher than adjacent normal-dysplasia and was significant (P<0.001). It was also higher as compared to nuclear pro-caspase-3 expression in tumor area (P<0.001). In overall assessment the cytoplasm expression of pro-caspase-3 was significantly higher than caspase-8 positivity in nucleus and cytoplasm.

Discussion: Caspase plays most important role in apoptosis, however its association with malignant transformation and prognosis is controversial. Cytoplasm expression of pro-caspase-3 in tumor region was significantly higher in comparison to adjacent normal epithelium and dysplasia. Since most of the pro-caspase-3 remains inactivated, its enhanced expression may be associated with poor prognosis in oral carcinoma.

A significant increase in nuclear caspase-8 in tumor area have been observed, the pro-caspase-3 may be directly activated in nucleus or are able to promote malignant progression by possibly assisting in mitotic cell division instead of assign the cells to p53-induced apoptosis. Thus possibly, altered caspases expression may be playing a decisive role in oral pharyngeal, multistep carcinoma progression.