Pathogenesis of Choriocarcinoma: Clinical, Genetic and Stem Cell Perspectives

Cheung, Annie N.Y.; Zhang, Hui Juan; Xue, Wei; Siu, Michelle K.Y.

doi:10.2217/14796694.5.2.217

Cited by 74 publications

(98 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A number of studies so far have linked the gestational choriocarcinoma with alterations in tumor suppressor genes, oncogenes or other imprinting genes (13). This study addresses some of the unresolved issues in the area of cancer endocrinology, as we provide novel evidence of a cross-talk of an inflammatory cytokine and a sex steroid hormone in choriocarcinoma.…”

Section: Discussionmentioning

confidence: 80%

Crucial cross-talk of interleukin-1β and progesterone in human choriocarcinoma

et al. 2012

View full text Add to dashboard Cite

Abstract. Choriocarcinoma is a highly malignant epithelial tumour that is most often associated with hydatidiform mole and presents the most common emergency medical problem in the management of trophoblast disease. We hypothesise that the hormones/cytokines present within the tumour microenvironment play key roles in the development of choriocarcinoma. In this study we assessed the effects of interleukin-1β (IL-1β) on cell death in the presence or absence of the sex hormone progesterone using two choriocarcinoma cell lines (BeWo and JEG-3) as in vitro experimental models. Although IL-1β induced cell death in both cell lines, the effect was more pronounced in JEG-3 cells, where cell death reached 40% compared to 15% in BeWo cells. Cell death of JEG-3 cells in response to IL-1β was significantly decreased by co-treatment with 100 nM and 1000 nM progesterone and completely abolished at a progesterone concentration of 1000 nM. Progesterone was also able to induce phosphorylation of ERK 1/2 in these cells. Pretreatment of JEG-3 cells with a specific MAPK inhibitor (UO126) inhibited progesterone's inhibitory effect on cell death. Collectively, these data provide evidence of cross-talk between progesterone and IL-1β in this aggressive and poorly understood tumour that involves activation of a MAPK pathway and involvement of numerous progesterone receptors. IntroductionGestational trophoblastic tumors are a group of diseases in which cancer (malignant) cells grow in the tissues that are formed following conception. They span from a benign hydatidiform mole, through an invasive mole to a highly malignant form of choriocarcinoma. Choriocarcinoma is malignant (both histologically and clinically) and is one of the most frequent emergency medical issues in the management disease of trophoblastic origin. The clinical symptoms vary, ranging from bleeding when the disease is localized in the uterus to a diverse repertoire of symptoms from metastases with the central nervous system, lungs, and liver the most frequent sites of secondary tumour formation. Therefore, choriocarcinomas present certain diagnostic challenges (1).Gestational choriocarcinoma is a highly malignant epithelial tumour that is most often associated with hydatidiform mole. On the occasions that pathology is available the characteristic findings exhibit the structure of the villous trophoblast but with sheets of syncytiotrophoblast or cytotrophoblast cells, haemorrhage, necrosis and intravascular growth are also common. A number of studies have shown involvement of certain tumourassociated genes in choriocarcinoma (1). For example, p53 oncoprotein immunoreactivity was significantly stronger in choriocarcinoma than in normal placenta (2). Studies from the same group revealed that c-myc, c-erbB-2, c-fms and bcl-2 oncoproteins may be important in the pathogenesis of complete mole and choriocarcinoma since they appear to be overexpressed in this aggressive tumour (3). The cellular mdm2 gene, which has a potential transforming activity that can be activated by over...

show abstract

Section: Discussionmentioning

confidence: 80%

Crucial cross-talk of interleukin-1β and progesterone in human choriocarcinoma

et al. 2012

View full text Add to dashboard Cite

show abstract

“…3 Choriocarcinoma frequently follows a complete hydatidiform mole which is characterized by exaggerated trophoblastic hyperplasia. 4 Previous morphological and immunohistochemical studies have suggested that choriocarcinoma develops as a result of neoplastic transformation of trophoblastic stem cells, presumably the cytotrophoblast. 1,5 The neoplastic cytotrophoblastic cells, like normal cytotrophoblasts on the villous surface of early placentas, differentiate into either extravillous (intermediate) trophoblast responsible for establishing the implantation site, or differentiate into syncytiotrophoblast which functions as a hormonal organ and regulates molecular exchange across the fetal-maternal interface.…”

mentioning

confidence: 99%

Trophoblastic vasculogenic mimicry in gestational choriocarcinoma

Shih

2011

Modern Pathology

View full text Add to dashboard Cite

Angiogenesis is a characteristic feature of solid tumors, which depend on the newly formed vasculature to prevent hypoxia and to sustain uncontrolled tumor cell proliferation. In this study, we investigated the blood supply system in 10 gestational choriocarcinomas on the basis of histopathological and immunohistochemical features. In all examined cases, morphological analysis demonstrated that blood channels within the center of choriocarcinomas were surrounded by neoplastic trophoblastic cells rather than by endothelial cells. Similarly, there was a lack of CD31 and CD34-positive endothelial cells within choriocarcinomas. In the periphery of choriocarcinomas, tumor cells invaded uterine stroma-derived blood vessels where trophoblastic cells replaced endothelial cells, forming anastomoses between endothelium-lined blood vessels and trophoblastlined pseudovascular channels. Masson's trichrome staining revealed minimal amounts of connective tissue within choriocarcinomas. In contrast, CD31 and CD34-positive blood vessels were present in other types of gestational trophoblastic neoplasms including 8 placental site trophoblastic tumors and 12 epithelioid trophoblastic tumors. These findings provide cogent evidence that choriocarcinoma represents one of a few human tumor types that utilizes vasculogenic mimicry by tumor cell in supporting tumor development.

show abstract

“…Although differences have been reported in the chemotherapy response, genetic origin and prognosis, gestational and non-gestational choriocarcinoma exhibit similar morphological pattern, histopathological classification and biochemical markers (4,15,16). Even with multidrug chemotherapy, a large number of patients with non-gestational choriocarcinoma died from the disease (16).…”

Section: Discussionmentioning

confidence: 99%

Successful detection of SRY gene via fine needle biopsy: A case of extragenital gestational choriocarcinoma in the kidney

et al. 2017

View full text Add to dashboard Cite

Abstract. The current report describes a case of extragenital gestational choriocarcinoma in the kidney. A 36-year-old woman with a history of two deliveries of male babies visited the present hospital due to secondary amenorrhea following a positive urinary pregnancy test. Despite a high serum level of human chorionic gonadotropin, at 51,800 mIU/ml, diagnostic imaging methods and pathological examination did not detect any conceptus in the genital tract. Positron emission tomography-computed tomography detected 18 F-FDG-positive tumors in the left kidney and right lung. A fine needle biopsy of the renal lesion pathologically revealed the presence of choriocarcinoma and a subsequent polymerase chain reaction analysis verified the presence of a Y-chromosome-specific the sex-determining region Y (SRY) gene, diagnosed as extragenital gestational choriocarcinoma. Clinically, 10 cycles of EMA/CO chemotherapy were administered and an optimal response was obtained. In conclusion, this is the first report of the diagnosis of extragenital gestational choriocarcinoma by the detection of the SRY gene with PCR using biopsy samples.

show abstract

Pathogenesis of Choriocarcinoma: Clinical, Genetic and Stem Cell Perspectives

Cited by 74 publications

References 86 publications

Crucial cross-talk of interleukin-1β and progesterone in human choriocarcinoma

Crucial cross-talk of interleukin-1β and progesterone in human choriocarcinoma

Trophoblastic vasculogenic mimicry in gestational choriocarcinoma

Successful detection of SRY gene via fine needle biopsy: A case of extragenital gestational choriocarcinoma in the kidney

Contact Info

Product

Resources

About