EXPRESSION OF P21 RAS PROTEIN AS A PROGNOSTIC FACTOR IN PAPILLARY THYROID-CANCER

We studied the expression of p21, the ras encoded protein, in primary tumour of 45 patients with papillary thyroid cancer (PTC). Patients we re grouped according to outcome so that one group (31 patients) had a good outcome and the other (14 patients) a fatal outcome, after a foll ow-up of at least 5 years. The presence of p21 ras protein was assesse d by immunohistochemistry with a specific monoclonal antibody (MAb Y-1 3259). The results were correlated with the outcome, with the expressi on of proliferating cell nuclear antigen (PCNA)/cyclin (as a marker of cell proliferation) and with other well established prognostic factor s for PTC (age, grading, extension and tumour size; Endocrinol Metab C lin North Am 1990, 19, 545-576). p21 staining in tumours of living pat ients was negative in 15, weakly positive (1+) in 10 and strongly posi tive (2+ or more) in 6 patients. In tumours from deceased patients, p2 1 staining was negative in 1, weakly positive in 2 and strongly positi ve in the remaining 11 patients (P < 0.001, (2)(chi)) PCNA immunostain ing was increased in 63.6% (7/11) of the tumours from deceased patient s compared to 17.8% (5/28) of the tumours of living patients, but no d irect correlation was found between p21 and PCNA expression. Among the other prognostic factors studied, only age greater than or equal to 4 0 years was a significant predictor of poor outcome. The survival curv e of patients with strongly positive p21 staining was similar to that of patients aged greater than or equal to 40 years at the time of diag nosis. The combination of p21 greater than or equal to 2+ and age grea ter than or equal to 40 was superior to age alone (P < 0.05) as a prog nostic indicator of poor outcome. In conclusion, our results indicate that the p21 product of the ras (proto)oncogene is differently express ed in PTC, in relation to the degree of aggressiveness. Regardless of the pathogenetic role of the ras oncogene in thyroid tumorigenesis, ou r data indicate that the expression of the p21 ras protein may be rega rded as a prognostic indicator in PTC. Furthermore, overexpression of p21 ras protein is associated with patients in the older age groups, a nd might contribute to the poor prognosis of elderly patients.