title: Proliferative activity and apoptosis in thymic epithelial neoplasms.
abstract: The classification of thymic epithelial tumors is controversial because prediction of the biological behavior of these tumors from their morphologic appearance is difficult. The aim of this study was to evaluate the proliferative activity and rate of apoptosis of thymic epithelial tumors classified according to World Health Organization histological classification. We also attempted to determine the importance of a number of proapoptotic factors in these processes. We investigated 46 surgically resected thymic epithelial tumors (8 Type A, 8 Type AB, 7 Type B1, 7 Type B2, 6 Type B3, and 10 Type C). Immunohistochemical staining was performed to determine the tumor expression of p53 protein, Bax, Bcl-2, and survivin. In addition, the Ki-67 labeling index (LI) and apoptotic index (AI) of these tumors were evaluated. Type C thymoma had a higher LI (16.55 +/- 12.12%) than did the other histological subtypes. Stage IV thymoma (12.36 +/- 9.99%) had a higher LI than did Stage I tumor. The AI was significantly elevated in Type B1 thymoma (1.47 +/- 0.55%). Overexpression of p53 protein was observed in Type B3 and C thymomas. p53 protein-positive tumors had a higher LI than did p53 protein-negative tumors (P <.0001). Bcl-2 expression was observed in Type A, AB, and C thymomas. Bcl-2-positive thymoma had a lower AI than did Bcl-2-negative thymoma (P =.0157). These results suggest that overexpression of p53 protein is associated with a higher tumor proliferative activity and that Bcl-2 acts as an inhibitor of apoptosis in thymoma. Bcl-2 and p53 protein expression may be useful markers in differentiating thymoma subtypes.
authors.affiliation: Department of Basic Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan. kenzo@med.m.chiba-u.ac.jp
authors.forename: Kenzo
authors.initials: K
authors.lastname: Hiroshima
authors.forename: Akira
authors.initials: A
authors.lastname: Iyoda
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Toyozaki
authors.forename: Yana
authors.initials: Y
authors.lastname: Supriatna
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Shibuya
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Shimamura
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Haga
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Yoshida
authors.forename: Takehiko
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Hidemi
authors.initials: H
authors.lastname: Ohwada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D002455:Cell Division; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis; D008875:Middle Aged; D009363:Neoplasm Proteins; D009367:Neoplasm Staging; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D000077022:Survivin; D013945:Thymoma / Q000378:metabolism / Q000473:pathology*; D013953:Thymus Neoplasms / Q000378:metabolism / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein