OBJECTIVE: Neurotrophins are known to exert a variety of pleiotropic responses in different target tissues, but little is known about their effect on thymic epithelial tumors. Therefore, we analyzed the expression of neurotrophin receptors in surgically resected thymic epithelial tumors and evaluated their clinical relevance. METHODS: The expression of neurotrophin receptors (Trk-A, Trk-B, Trk-C and p75(NTR)) in thymic epithelial tumors was evaluated in 99 consecutive patients based on immunohistochemical staining. The pattern of expression was analyzed according to the WHO classification, and survival outcomes were estimated. RESULTS: Thymic tumors were classified as type A (n=6), AB (n=21), B1 (n=15), B2 (n=24), B3 (n=22) or C (n=11). All tumors, except one type C thymoma, demonstrated cytoplasmic Trk-A immunostaining, and no thymic tumors showed Trk-B or Trk-C immunoreactivity. p75(NTR) immunostaining demonstrated characteristic patterns according to the WHO subtypes of thymomas. All type A and type AB thymomas showed p75(NTR) immunoreactivity, except one type A tumor. The expression of p75(NTR) was negative in 6 patients (40%) with type B1 thymomas, 19 patients (79.2%) with type B2 thymomas, 17 patients (77.3%) with type B3 thymomas and 10 patients (90.9%) with type C thymomas. Tumor-related survival at 5 and 10 years was 95.5 and 89.5%, respectively, in p75(NTR)-positive thymomas and 82.8 and 77.2%, respectively, in p75(NTR)-negative thymomas; however, the differences were not statistically significant (P=0.14). CONCLUSIONS: Among the neurotrophin receptors examined, the pattern of p75(NTR) expression closely correlated with the WHO subtypes of thymomas. Further study of p75(NTR) expression may aid in understanding the biology of thymic epithelial tumors.
OBJECTIVE: Neurotrophins are known to exert a variety of pleiotropic responses in different target tissues, but little is known about their effect on thymic epithelial tumors. Therefore, we analyzed the expression of neurotrophin receptors in surgically resected thymic epithelial tumors and evaluated their clinical relevance. METHODS: The expression of neurotrophin receptors (Trk-A, Trk-B, Trk-C and p75(NTR)) in thymic epithelial tumors was evaluated in 99 consecutive patients based on immunohistochemical staining. The pattern of expression was analyzed according to the WHO classification, and survival outcomes were estimated. RESULTS: Thymic tumors were classified as type A (n=6), AB (n=21), B1 (n=15), B2 (n=24), B3 (n=22) or C (n=11). All tumors, except one type C thymoma, demonstrated cytoplasmic Trk-A immunostaining, and no thymic tumors showed Trk-B or Trk-C immunoreactivity. p75(NTR) immunostaining demonstrated characteristic patterns according to the WHO subtypes of thymomas. All type A and type AB thymomas showed p75(NTR) immunoreactivity, except one type A tumor. The expression of p75(NTR) was negative in 6 patients (40%) with type B1 thymomas, 19 patients (79.2%) with type B2 thymomas, 17 patients (77.3%) with type B3 thymomas and 10 patients (90.9%) with type C thymomas. Tumor-related survival at 5 and 10 years was 95.5 and 89.5%, respectively, in p75(NTR)-positive thymomas and 82.8 and 77.2%, respectively, in p75(NTR)-negative thymomas; however, the differences were not statistically significant (P=0.14). CONCLUSIONS: Among the neurotrophin receptors examined, the pattern of p75(NTR) expression closely correlated with the WHO subtypes of thymomas. Further study of p75(NTR) expression may aid in understanding the biology of thymic epithelial tumors.
Authors: Glen J Weiss; Manuel Hidalgo; Mitesh J Borad; Daniel Laheru; Raoul Tibes; Ramesh K Ramanathan; Lisa Blaydorn; Gayle Jameson; Antonio Jimeno; Jeffrey D Isaacs; Angela Scaburri; Maria Adele Pacciarini; Francesco Fiorentini; Marina Ciomei; Daniel D Von Hoff Journal: Invest New Drugs Date: 2011-12-09 Impact factor: 3.850