Gestational choriocarcinoma is a highly malignant epithelial tumor that can be associated with any type of gestational event, most often a complete hydatidiform mole. Choriocarcinoma recapitulates the differentiation of cytotrophoblastic cells in early gestation. It may arise from neoplastic transformation of CT. Neoplastic CT, similar to its normal counterpart, retains its capacity to differentiate into ST and IT. As an intimate mixture of CT, IT, and ST is characteristic of choriocarcinoma. The CT and IT tend to grow in clusters and sheets, separated by ST, forming the characteristic dimorphic growth pattern of mononucleate trophoblast and ST. In choriocarcinoma, the percent of IT, as defined by CD146 (Mel-CAM) positive trophoblastic cells, is highly variable ranging from 1 to 90% of the mononucleate trophoblastic cellular population (25). The preliminary findings using immunohistochemical staining for p-catenin in choriocarcinoma demonstrate that p-catenin is localized in the nucleus in CT in contrast to its localization on the cell membrane in the adjacent IT. This pattern is similar to the distribution of p-catenin in the CT in the normal placenta. This finding suggests that p-catenin translocation to the nucleus may contribute to the cellular proliferation of tro-phoblastic cells in choriocarcinoma.
Choriocarcinoma has no intrinsic vascular stroma; the tumor receives its vascular supply by vascular invasion exclusively. However, infiltrative growth of normal tissues and blood vessels can give the appearance of a vascular framework (26). The "pseudovasculogenesis" without neovasculogenesis permits an efficient blood supply to the tumor and contributes to the rapid growth of choriocarcinoma. This in vivo observation can be experimentally demonstrated in animals. The human choriocarcinoma cell line, JEG-3 when established in the subcutaneous tissue of mice, grows rapidly, forms intricate "vascular" channels lined by JEG-3 trophoblastic cells and not with host endothelial cells, and replaces the normal endothelium within the tumor xenograft (27). This animal model might be useful for experimental studies of the biology of chorio-carcinoma, especially, the process of "pseudovasculogenesis."
As in complete moles, synergistic upregulation of c-myc, c-erb-2, c-fms, and bcl-2 oncoproteins appears to play an important role in the pathogenesis of choriocarcinoma (28). Mutational analysis of K-ras and p53 has failed to show mutations of these genes in choriocarcinoma (28-30), although overexpression of p53 has occasionally been found in choriocarcinoma (31). The other genes that are potentially involved in the development of choriocarcinoma include DOC-2/hDab2, a candidate tumor suppressor gene (32,33), and a putative tumor suppressor gene(s) located on chromosome 7p12-7q11.23 (34). Also, the ras GTPase activating protein (35) and HLA-G, which may participate in escape of immunosurvellance of tumor cells (36).
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