Maspin in thyroid cancer: its relationship with p53 and clinical outcome

The serine protease inhibitor maspin has been reported to inhibit invasiveness and motility of tumor cells. Additionally, a p53-dependent regulatory pathway of maspin in human cancer has been indicated. In a pre-study we were able to detect maspin protein in papillary thyroid carcinomas (PTC), whereas normal (tumor-free) thyroid tissue, follicular adenomas, follicular carcinomas, poorly differentiated carcinomas and undifferentiated carcinomas of the thyroid were maspin-negative. The first aim of our study was to determine the prognostic value of maspin protein expression for the recurrence-free and overall survival of PTC patients undergoing radical thyroidectomy and postoperative irradiation. Secondly, maspin expression was correlated to p53 protein expression in order to gain additional information on a possible regulatory influence of the wild-type p53 protein on maspin. An immunohistochemical approach study was performed on 68 tumor specimens. Maspin protein expression was detectable in 48 of 68 patients (71%; M+). After a median follow-up of 81 (26-117) months the median recurrence-free survival was 60 (28-117) months for M+ and 42 (11-108) months for M- (p=0.03). After 110 months 83% of patients had recurrence-free disease in M+, whereas in M- only 40% of patients were recurrence-free. The median long-term survival was 81 (42-108) months for M+ and 55 (21-99) months for M- (p=0.03). After 5 years, M+ and M- patients had a total survival of 98 and 80%, and after 9 years 90 and 60%, respectively. Mutant-type p53 expression was detectable in 17 of 68 PTC (25%). Mt p53 was positive in 1 of 47 M+ (2%) compared with 16 of 20 M- (80%, p<0.01). This study indicates that maspin protein possibly functions as a clinically relevant inhibitor of tumor progression, preventing local invasiveness and further systemic progression of papillary thyroid carcinomas. Our data hint of a p53-dependent regulatory pathway of the maspin protein in human cancer.