Apoptosis and proliferative activity in mature and immature teratomas of the mediastinum.
BACKGROUND
Mediastinal teratomas are the most frequent mediastinal germ cell tumor. Whereas mature teratomas are benign tumors, immature teratomas are malignant. The purpose of this study was to find characteristics that could be used to distinguish between the growth and prognosis of the two teratoma types.


METHODS
Twenty-four mediastinal teratomas (18 mature and 6 immature) were examined for apoptosis by 3'-end labeling of DNA and stained immunohistochemically for proliferating cell nuclear antigen, Bcl-2, Bax, p53 protein, and alpha-fetoprotein (AFP) expression in formalin fixed, paraffin embedded specimens.


RESULTS
AFP was expressed in both immature teratomas and mature teratomas. Whereas p53 protein was expressed by most teratomas, p53 gene mutation was observed in only one patient with an immature teratoma in which the same mutation occurred in all tumor tissue components tested. Bax protein expression was relatively diffuse in mature teratomas but was focally expressed in immature teratomas. Bcl-2 protein was expressed focally in both mature and immature teratomas. Although the proliferative index was significantly higher in immature teratomas compared with mature teratomas (P < 0.001), the apoptotic index (AI) was significantly higher in mature teratomas compared with immature teratomas (P < 0.05). All patients except one in this study remain alive and disease free after undergoing tumor resection.


CONCLUSIONS
The relatively high AI in mature teratomas may be due to the overexpression of the p53 protein. In contrast, immature teratomas exhibited higher proliferative activity and lower rates of apoptosis, which may explain the more aggressive behavior of these tumors. However, patients with immature mediastinal teratomas have a good prognosis if the tumor is resected completely after chemotherapy.
Hiroshima
K
K
Division of Pathology, Institute of Pulmonary Cancer Research, Chiba University School of Medicine, 1-8-1 Inohona, Chuo-ku, Chiba, 260-8670 Japan. kenzo@med.m.chiba-u.ac.jp
Toyozaki
T
T
Iyoda
A
A
Yusa
T
T
Fujisawa
T
T
Ohwada
H
H
D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D002455:Cell Division; D002648:Child; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008479:Mediastinal Neoplasms / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013724:Teratoma / Q000145:classification / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D004273:DNA, Neoplasm; D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D000509:alpha-Fetoproteins; D051028:bcl-2-Associated X Protein