By comparing candidate driving genes between AYA cancers and those from all age groups for the same type of cancer, we identified different driving genes in prostate cancer and a germ cell tumor in AYAs compared with all age groups, whereas three common alterations (TP53, FAT1, and NOTCH1) in head and neck cancer were identified in both groups.
The Mdm2 inhibitor nutlin-3 was evaluated alone and in combination with cisplatin in a panel of germ cell tumour (GCT)-derived cell lines (embryonal carcinomas, being the nonseminomatous stem-cell component) with wild-type (NT2 and 2102EP cells) and mutant (NCCIT cells) p53 status.
The expression of p53 (mutation) in ovarian epithelial cancers (56.6%) was significantly higher than that in the malignant germ cell tumors of the ovary (28%), whereas the expression of Bcl-2 and Topo II alpha had no significant difference between the 2 groups.
The data indicate that robust transcriptional activation of p53 is linked to the known hypersensitivity of testicular germ cell tumors to chemotherapy.
None of the remaining eight cases with frequent positive cells, the nine cases with occasionally positive p53 staining, or the two cases with no staining recurred or demonstrated other germ cell tumor elements.
Recent data underline the need to seek further explanations, other than the previously postulated high intrinsic level of wild-type P53 protein, for the exquisite curability of germ-cell tumors.
Cluster analysis of p53 and Ki67 expression, apoptosis, alpha-fetoprotein, and human chorionic gonadotrophin indicates a favorable prognostic subgroup within the embryonal carcinoma germ cell tumor.
Overexpression of p53 was not observed in all of the 22 ovarian germ cell tumors; only 3 were found to have nuclear staining in a small fraction of the malignant cells (< 5% in 1 immature teratoma, 5-10% in 2 yolk-sac tumors).
Using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis, p53 gene mutation was examined in 12 intracranial germ cell tumors (5 yolk sac carcinomas and 7 germinomas), many of which were derived from young patients in the first to the second decade.
The P53 tumor suppressor gene protein is expressed to some degree in most testicular germ cell tumors and degree of staining/expression varies according to stage of disease.