Clear Cell Carcinoma of the Ovary: A Distinct Histologic Type with Poor Prognosis and Resistance to Platinum-Based Chemotherapy in Stage III Disease

Goff, Barbara A.; Cuesta, Ricardo Sáinz de la; Muntz, Howard G.; Fleischhacker, Deborah S.; Ek, Marit; Rice, Laurel W.; Nikrui, Najmosama; Tamimi, Hisham K.; Cain, Joanna M.; Greer, Benjamin E.; Fuller, Arlan F.

doi:10.1006/gyno.1996.0065

Cited by 312 publications

(242 citation statements)

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“…We have recently reported clear cell histology as a strong risk factor for VTE before treatment in ovarian cancer , and clear cell carcinoma shows significantly stronger expression of tissue factor, a major factor in the procoagulant activities of cancer cells, as compared with non-clear cell carcinoma . Several published reports support the association between clear cell histology and VTE in ovarian cancer (Goff et al, 1996;Recio et al, 1996). These reports have postulated that patients with clear cell histology display a significantly higher incidence (11 -42%) of VTE as compared with those with non-clear cell histology in the immediate postoperative period and during primary chemotherapy.…”

Section: Discussionmentioning

confidence: 86%

Silent venous thromboembolism before treatment in endometrial cancer and the risk factors

et al. 2008

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Venous thromboembolism (VTE) often occurs after surgery and can even occur before surgery in patients with gynaecological malignancies. We investigated the incidence of VTE before treatment of endometrial cancer and associated risk factors. Plasma D-dimer (DD) levels before initial treatment were examined in 171 consecutive patients with endometrial cancer. Venous ultrasound imaging (VUI) of the lower extremities was performed in patients with DD X1.5 mg ml À1 , as the negative predictive value of DD for VTE is extremely high. For patients with deep vein thrombosis (DVT), pulmonary scintigraphy was performed to ascertain the presence of pulmonary thromboembolism (PTE). Risk factors for VTE were analysed using univariate and multivariate analyses for 171 patients. Of these, 37 patients (21.6%) showed DD X1.5 mg ml À1 , 17 (9.9%) displayed DVT by VUI and 8 (4.7%) showed PTE on pulmonary scintigraphy. All patients with VTE were asymptomatic. Univariate analysis for various risk factors revealed older age, non-endometrioid histology and several variables of advanced disease as significantly associated with VTE before treatment. Obesity, smoking and diabetes mellitus were not risk factors. Multivariate analysis confirmed extrauterine spread and non-endometrioid histology as independently and significantly associated with risk of VTE. These data suggest that silent or subclinical VTE occurs before treatment in at least around 10% of patients with endometrial cancer. Risk factors for VTE before treatment might not be identical to those after starting treatment.

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Section: Discussionmentioning

confidence: 86%

Silent venous thromboembolism before treatment in endometrial cancer and the risk factors

et al. 2008

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“…To date, patients with clear cell carcinoma have a significantly worse prognosis than patients with non-clear cell carcinomas, because of their low response to standard platinum-based chemotherapy. 21 HNF-1beta might be a specific molecular target for therapy of ovarian clear cell carcinomas in the future.…”

Section: Discussionmentioning

confidence: 99%

Expression of hepatocyte nuclear factor-1beta (HNF-1beta) in clear cell tumors and endometriosis of the ovary

2006

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Clear cell tumors of the ovary are frequently associated with ovarian endometriosis. Clinicopathologically, it has been suggested that clear cell tumors develop from endometriosis, but there has been little molecular evidence supporting this speculation. Microarray analysis revealed recently that hepatocyte nuclear factor1beta (HNF-1beta) was significantly upregulated in clear cell carcinoma of the ovary. In the present study, we examined 30 clear cell tumors (26 malignant, three borderline, and one benign) and 40 endometriotic cysts to clarify if differentiation into the clear cell lineage already begins in ovarian endometriosis. All of the 30 clear cell tumors, including borderline and benign ones, showed immunohistochemical expression of HNF-1beta in the nucleus, while other types of ovarian epithelial tumors (endometrioid, serous, mucinous, and Brenner tumors) rarely expressed it. Among 30 clear cell tumors, 17 (56%) cases were associated with endometriosis, and endometriotic epithelium was identified in 12 cases. In nine of the 12 cases, distinct nuclear immunostaining for HNF-1beta was detected in the endometriotic epithelium, as well as in the clear cell tumor. HNF-1beta expression was observed either in atypical endometriosis (four cases), or in endometriosis of a reactive nature (five cases). Furthermore, 16 of 40 (40%) endometriotic cysts without a neoplasm also expressed HNF-1beta, and the expression was almost exclusively observed in the epithelium showing inflammatory atypia. Our results indicate that HNF-1beta is an excellent molecular marker for ovarian clear cell tumors, including benign, borderline and malignant lesions. Early differentiation into the clear cell lineage takes place in ovarian endometriosis, not only in atypical endometriosis, but also in endometriosis with degenerative and regenerative changes, and this is probably responsible for the frequent occurrence of clear cell carcinoma in ovarian endometriosis. Keywords: ovary; clear cell tumor; endometriosis; hepatocyte nuclear factor-1beta; histogenesis Among malignant epithelial tumors of the ovary, clear cell carcinomas, as well as endometrioid adenocarcinomas, are most frequently associated with ovarian endometriosis. The frequency of endometriosis is reportedly between 21 and 54% in large series of clear cell carcinomas. [1][2][3][4][5] In addition, an atypical glandular change in endometriosis, the socalled atypical endometriosis, is often present associated with clear cell carcinomas, while it is rare in endometriosis without a neoplasm. 2,6,7 Thus, many clinicopathological studies have strongly suggested a malignant transformation of endometriosis to clear cell carcinomas, but little molecular evidence exists to support the notion that endometriosis is the precursor of clear cell carcinomas. A molecular genetic study showed that ovarian endometriosis and its adjacent carcinoma shared a common allelotype; however, few clear cell carcinomas were subjected to this study. 8 Recently, a study using an oligonucleotide array technique...

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“…This type of ovarian tumour represents a distinct histological type where the overall prognosis for patients is poor in comparison with other histologies. The outcome is largely due to the poor response to conventional platinum-based chemotherapy such as cisplatin (Goff et al, 1996;Makar et al, 1995;Tanmella et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Analysis of the TGF β functional pathway in epithelial ovarian carcinoma

Francis-Thickpenny

Richardson

et al. 2001

Br J Cancer

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Summary Epithelial ovarian carcinoma is often diagnosed at an advanced stage of disease and is the leading cause of death from gynaecological neoplasia. The genetic changes that occur during the development of this carcinoma are poorly understood. It has been proposed that IGFIIR, TGFβ1 and TGFβRII act as a functional unit in the TGFβ growth inhibitory pathway, and that somatic loss-of-function mutations in any one of these genes could lead to disruption of the pathway and subsequent loss of cell cycle control. We have examined these 3 genes in 25 epithelial ovarian carcinomas using single-stranded conformational polymorphism analysis and DNA sequence analysis. A total of 3 somatic missense mutations were found in the TGFβRII gene, but none in IGFRII or TGFβ1. An association was found between TGFβRII mutations and histology, with 2 out of 3 clear cell carcinomas having TGFβRII mutations. This data supports other evidence from mutational analysis of the PTEN and β-catenin genes that there are distinct developmental pathways responsible for the progression of different epithelial ovarian cancer histologic subtypes.

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Clear Cell Carcinoma of the Ovary: A Distinct Histologic Type with Poor Prognosis and Resistance to Platinum-Based Chemotherapy in Stage III Disease

Cited by 312 publications

References 4 publications

Silent venous thromboembolism before treatment in endometrial cancer and the risk factors

Silent venous thromboembolism before treatment in endometrial cancer and the risk factors

Expression of hepatocyte nuclear factor-1beta (HNF-1beta) in clear cell tumors and endometriosis of the ovary

Analysis of the TGF β functional pathway in epithelial ovarian carcinoma

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