Apoptosis in colorectal cancer : evaluation as a potential prognostic marker and its relationship to proteins that regulate the cell cycle
Apoptosis is the phenomenon of single cell death which is morphologically and biologically distinct from necrosis. Apoptosis is widely observed in embryological, physiological and pathological situations, including neoplasia. It might be expected that apoptosis could be related to prognosis of tumours, as loss of cells through apoptosis provides a counter to tumour growth. Furthermore, it has hypothesised that cells from tumours which exhibit less apoptosis have a better ability to grow as metastatic deposits than cells from tumours that readily undergo apoptosis. Therefore, it was elected to evaluate apoptosis as a potential prognostic variable in colorectal cancer, with the expectation that low apoptotic indices would be unfavourable. Patients aged 45 years and under with tumours that had low apoptotic indices did exhibit a poor survival. However, patients aged over 45 years showed no association between apoptosis and outcome; but, in a subgroup aged over 65 years it was found that a low apoptotic index was associated with a good prognosis. The contradictory results between tumours in the young and old may indicate these are biologically different lesions. Evaluation of apoptosis compared to more traditional prognostic variables revealed that extramural invasion of veins was consistently a significant marker of poor prognosis. No evidence was found to support the contention that there is a decrease in apoptosis as tumours acquire malignant potential. Although there was a lower apoptotic index in the tumours from patients aged 45 years and under which stained for p53 protein compared to those that did not, no associations were found between apoptosis and p21, cyclin D1, cyclin D3 or cyclin E. In conclusion apoptosis would not appear to be a generally applicable prognostic variable in colorectal cancer, whereas invasion of extramural veins by tumour would appear to be a consistent indicator of poor prognosis.