title: Maspin in thyroid cancer: its relationship with p53 and clinical outcome.
abstract: 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.
authors.affiliation: Department of Pathology, Otto-von-Guericke University, D-39120 Magdeburg, Germany. carsten.boltze@medizin.uni-magdeburg.de
authors.forename: Carsten
authors.initials: C
authors.lastname: Boltze
authors.forename: Regine
authors.initials: R
authors.lastname: Schneider-Stock
authors.forename: Frank
authors.initials: F
authors.lastname: Meyer
authors.forename: Brigitte
authors.initials: B
authors.lastname: Peters
authors.forename: Claudia
authors.initials: C
authors.lastname: Quednow
authors.forename: Cuong
authors.initials: C
authors.lastname: Hoang-Vu
authors.forename: Albert
authors.initials: A
authors.lastname: Roessner
mesh_terms: D000328:Adult; D000368:Aged; D001665:Binding Sites; D002277:Carcinoma / Q000378:metabolism*; D002291:Carcinoma, Papillary / Q000378:metabolism*; D002454:Cell Differentiation; D002470:Cell Survival; D018572:Disease-Free Survival; D005260:Female; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D011506:Proteins / Q000378:metabolism / Q000502:physiology*; D012008:Recurrence; D015843:Serpins / Q000378:metabolism / Q000502:physiology*; D013964:Thyroid Neoplasms / Q000378:metabolism*; D013997:Time Factors; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D011506:Proteins; C085344:SERPIN-B5; D015843:Serpins; D016159:Tumor Suppressor Protein p53