Boltze Carsten, Schneider-Stock Regine, Meyer Frank, Peters Brigitte, Quednow Claudia, Hoang-Vu Cuong, Roessner Albert
Department of Pathology, Otto-von-Guericke University, D-39120 Magdeburg, Germany.
Oncol Rep. 2003 Nov-Dec;10(6):1783-7.
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.
据报道，丝氨酸蛋白酶抑制剂组织蛋白酶抑制因子（maspin）可抑制肿瘤细胞的侵袭性和运动性。此外，还发现了人类癌症中maspin的p53依赖性调节途径。在一项前期研究中，我们能够在甲状腺乳头状癌（PTC）中检测到maspin蛋白，而正常（无肿瘤）甲状腺组织、滤泡性腺瘤、滤泡性癌、低分化癌和未分化癌的甲状腺组织中maspin呈阴性。我们研究的首要目的是确定maspin蛋白表达对接受根治性甲状腺切除术和术后放疗的PTC患者无复发生存率和总生存率的预后价值。其次，将maspin表达与p53蛋白表达相关联，以获取关于野生型p53蛋白对maspin可能的调节影响的更多信息。对68个肿瘤标本进行了免疫组织化学方法研究。68例患者中有48例（71%；M+）可检测到maspin蛋白表达。中位随访81（26 - 117）个月后，M+组的中位无复发生存期为60（28 - 117）个月，M-组为42（11 - 108）个月（p = 0.03）。110个月后，M+组83%的患者无疾病复发，而M-组只有40%的患者无复发。M+组的中位长期生存率为81（42 - 108）个月，M-组为55（21 - 99）个月（p = 0.03）。5年后，M+组和M-组患者的总生存率分别为98%和80%，9年后分别为90%和60%。68例PTC中有17例（25%）可检测到突变型p53表达。47例M+中有1例（2%）Mt p53呈阳性，而20例M-中有16例（80%，p < 0.01）。本研究表明，maspin蛋白可能作为一种与临床相关的肿瘤进展抑制剂，防止甲状腺乳头状癌的局部侵袭和进一步的全身进展。我们的数据提示了人类癌症中maspin蛋白的p53依赖性调节途径。
