A team of doctors in Ireland and Italy measured the expression of the tumor suppressor protein p16/INK4A in tumor biopsy specimens from 88 pleural mesothelioma patients. P16 plays an important role in cell cycle regulation, slowing down the progression of cells from the first phase, during which cells make mRNA and proteins, to the S1 phase during which DNA is replicated.
The team found that the greater the expression of p16, the better the odds of mesothelioma survival. At the same time, mesothelioma patients with lower p16 levels were less likely to have a positive outcome.
“Those cases with intermediate or high p16/INK4A tumour expression had a significantly better post-diagnosis survival than those cases whose tumours lost p16 expression,” writes Cormac J. Jennings of Beaumont Hospital in Dublin, Ireland.
Of the 88 mesothelioma cases evaluated, just over half were classified as having low p16 expression. Thirty-one percent were classified in the intermediate range and 17 percent (15 patients) had high p16 expression, giving them the best prospects for survival.
According to the research, not only did high p16 appear to help keep mesothelioma tumors from growing as quickly, but it also made them more susceptible to the effects of chemotherapy. Mesothelioma patients with the highest p16 levels who had chemotherapy lived longer than patients whose tumors had lost p16 expression, even if they also had chemotherapy.
P16 levels in mesothelioma tissue samples are measured using a type of testing called immunohistochemistry. P16 deletion or mutation has been associated with poor survival in a number of other cancers including melanoma and cervical cancer.
Jennings, CJ et al, “Differential p16/INK4A cyclin-dependent kinase inhibitor expression correlates with chemotherapy efficacy in a cohort of 88 malignant pleural mesothelioma patients”, June 9, 2015, British Journal of Cancer, ePub ahead of print, June 9, 2015