Apoptosis regulation and spontaneous apoptosis index of testicular germ cell tumors are associated with differentiation and resistance to systemic treatment.
BACKGROUND
Cisplatin-based chemotherapy can cure more than 80% of metastatic germ cell testicular tumors (GCT). Germ cells are particularly susceptible to apoptosis and it is reasonable to presume that GCTs are curable because of an intact and effective apoptotic pathway.


METHODS
The expression of p53 and p21 was investigated in conjunction with the spontaneous apoptotic index in 20 refractory and 50 chemosensitive GCTs, with a complete follow-up. To detect a differentiation-dependent alteration in the apoptotic pathway, all of the histological tumor types were examined separately.


RESULTS
Embryonal carcinoma components showed significantly higher p53 expression compared to other histological subtypes of GCTs. p21 was barely detectable in the majority of tumors. Seminomatous components showed no p21 expression. Mature teratomas and syncytiotrophoblasts showed significantly higher p21 expression than other tumor subtypes. Embryonal carcinomas showed significantly higher apoptotic indices than other non-seminomatous components. On the other hand, choriocarcinomas and mature teratomas showed the lowest spontaneous apoptotic potential. The apoptotic index correlated with the fraction of p53-positive cells, but not with the p21 expression rate. The refractory group showed significantly lower p53 expression, higher p21 expression and a higher apoptosis index than the sensitive group.


CONCLUSIONS
Our results suggest that the p53 and p21 expression levels and the apoptosis index seem to be important factors in the issue of the chemosensitivity of GCTs. The protein expression pattern reflects a differentiation-dependent preference for G1/S-phase arrest in terminally differentiated syncytiotrophoblasts and mature teratoma cells, while p53 mediated apoptosis induction is meaning to less differentiated tumor types.
Mandoky
László
L
Department of Cytopathology, National Institute of Oncology, Budapest, Hungary.
Szende
Béla
B
Géczi
Lajos
L
Bodrogi
István
I
Kásler
Miklós
M
Bak
Mihály
M
D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53