Mucinous Epithelial Ovarian Cancer: A Separate Entity Requiring Specific Treatment

Hess, Viviane; A’Hern, Roger; Nasiri, N.; King, David M.; Blake, Peter; Barton, Desmond P.J.; Shepherd, John H.; Ind, Thomas; Bridges, Jackie; Harrington, Kevin; Kaye, Stanley B.; Gore, Martin

doi:10.1200/jco.2004.08.078

Cited by 298 publications

(215 citation statements)

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“…In addition, the high level of LGALS4 expression in MOC may aid in the histological differentiation of primary MOC from metastatic ovarian carcinoma arising at other sites (Heinzelmann-Schwarz et al; manuscript submitted for publication). As previously suggested (Hess et al, 2004), the obvious genetic similarities of MOC with mucinous-type intestinal carcinomas support a move toward the use of a therapeutic approach tailored to the molecular characteristics of MOC rather than the tissue of origin. Patients with advanced stage MOC generally receive the same adjuvant chemotherapy as the other subtypes of ovarian carcinoma, normally a platinum-based approach combined with paclitaxel.…”

Section: Discussionmentioning

confidence: 80%

“…Using GenMAPP analysis, we examined if any probesets corresponding to other members of the mitogen activated protein (MAP) kinase cascade were differentially expressed in MOC compared to the other subtypes of ovarian cancer. This revealed a slight increase in ERK1 (1.19-fold change, unadjusted Po0.001) and a two-fold decrease in MAP kinase kinase 1 (MEKK1) expression (0.61-fold change, unadjusted P ¼ 0.03), the latter being linked to cisplatin-resistance in ovarian cancer (Gebauer et al, 2000), a feature of MOC (Hess et al, 2004).…”

Section: Cellular Pathways Underlying Moc Developmentmentioning

confidence: 99%

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A distinct molecular profile associated with mucinous epithelial ovarian cancer

et al. 2006

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Mucinous epithelial ovarian cancers (MOC) are clinically and morphologically distinct from the other histological subtypes of ovarian cancer. To determine the genetic basis of MOC and to identify potential tumour markers, gene expression profiling of 49 primary ovarian cancers of different histological subtypes was performed using a customised oligonucleotide microarray containing 459 000 probesets. The results show that MOC express a genetic profile that both differs and overlaps with other subtypes of epithelial ovarian cancer. Concordant with its histological phenotype, MOC express genes characteristic of mucinous carcinomas of varying epithelial origin, including intestinal carcinomas. Differences in gene expression between MOC and other histological subtypes of ovarian cancer were confirmed by RT -PCR and/or immunohistochemistry. In particular, galectin 4 (LGALS4) was highly and specifically expressed in MOC, but expressed at lower levels in benign mucinous cysts and borderline (atypical proliferative) tumours, supporting a malignant progression model of MOC. Hence LGALS4 may have application as an early and differential diagnostic marker of MOC.

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Section: Discussionmentioning

confidence: 80%

Section: Cellular Pathways Underlying Moc Developmentmentioning

confidence: 99%

A distinct molecular profile associated with mucinous epithelial ovarian cancer

et al. 2006

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“…It has been suggested that other treatments used in mucinous gastrointestinal carcinomas might be more useful. 17 Preclinical data have suggested a synergism of oxaliplatin and 5-fluorouracil in cisplatin-resistant experimental models. 18 This synergism results from down-regulation of the excision-repair cross-complementation group 1 by 5-fluorouracil, resulting in enhanced sensitivity to oxaliplatin.…”

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confidence: 99%

Mucinous but not clear cell histology is associated with inferior survival in patients with advanced stage ovarian carcinoma treated with platinum‐paclitaxel chemotherapy

Bamias

Ψαλτοπούλου

Sotiropoulou

et al. 2010

Cancer

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BACKGROUND: Mucinous and clear cell histology have been associated with adverse prognosis in ovarian carcinomas. The authors compared the outcome of these subtypes with that of serous tumors in patients who were treated with combination paclitaxel/platinum at their center. METHODS: Four hundred twenty patients with histologically confirmed, serous (n ¼ 367), mucinous (n ¼ 24), or clear cell (n ¼ 29) ovarian carcinomas, International Federation of Gynecology and Obstetrics stage III or IV disease, and who were treated with paclitaxel/platinum after cytoreductive surgery were included in this analysis. RESULTS: The median overall survival for each histological subtype was 47.7 months (95% confidence interval [CI], 37.7-57.7 months) for serous, 15.4 months (95% CI, 4.2-26.6 months) for mucinous, and 36.6 months (95% CI, 22.7-50.5 months) for clear cell carcinomas. Cox regression analysis showed that mucinous histology was an independent predictor of poor prognosis compared with serous tumors (hazard ratio, 0.360; 95% CI, 0.215-0.603; P ¼ .001). In contrast, such a difference between clear cell and serous carcinomas was not found (P ¼ .337). Median survival of patients with mucinous tumors and residual disease >2 cm was poor, averaging 7.1 months (95% CI, 4.6-9.6 months). CONCLUSIONS: Mucinous but not clear cell histology is associated with significantly worse prognosis in advanced ovarian cancer treated with combination platinum/paclitaxel. Different therapeutic strategies should be studied in this entity.

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“…In 2004, Hess et al showed that women with advanced-stage mucinous ovarian cancers had a worse prognosis than women with nonmucinous epithelial ovarian cancers. 3 In contrast, type II tumors grow rapidly and are highly aggressive neoplasms for which well-defined precursor lesions have not been described. Most are at an advanced staged either during or soon after their inception.…”

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confidence: 99%

Molecular typing of epithelial ovarian carcinomas using inflammatory markers

Ali-Fehmi

Semaan

Sethi

et al. 2010

Cancer

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BACKGROUND: Ovarian epithelial carcinomas have recently been classified as slow growing type I tumors and rapidly growing highly aggressive type II tumors. The present study sought to molecularly characterize type I and II tumors using known molecular markers. METHODS: Specimens from 213 patients with ovarian carcinoma were categorized as type I or type II, and evaluated by immunohistochemistry for the inflammatory markers glucose transporter protein-1 (Glut-1), inducible nitric oxide synthase (iNOS), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and nuclear factor kappa B. Statistical analysis was performed to investigate whether these molecular markers could distinguish between type I and type II tumors. Kaplan-Meier survival curves and COX regression analysis were used to determine the prognostic effect of these markers on survival in the 2 types of tumors. RESULTS: Overexpression of COX-1, COX-2, iNOS, and Glut-1 was significantly higher in type II tumors (P < .05). Women with type II tumors had a poorer median survival (60 months) as compared with those with type I tumors (141 months) (P ¼.0001). Multivariate analysis revealed type II tumors, late stage, and age >60 years as significant predictors of poor survival. For type II tumors, median survival of patients with tumors overexpressing COX-2 was 44 compared with 85 months for those with tumors with low COX-2 expression (P ¼.029). Looking at both type I and II tumors, the number of markers simultaneously overexpressed in each tumor was a significant predictor of poor patient survival (P ¼.005). CONCLUSIONS: The present study demonstrates that the new proposed histologic classification of ovarian epithelial carcinomas correlates with a distinct expression of inflammatory pathway proteins. High expression of these markers may explain the different biologic behavior of these 2 tumor types and provide targets for therapy. Cancer 2011;117:301-9.

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Mucinous Epithelial Ovarian Cancer: A Separate Entity Requiring Specific Treatment

Cited by 298 publications

References 20 publications

A distinct molecular profile associated with mucinous epithelial ovarian cancer

A distinct molecular profile associated with mucinous epithelial ovarian cancer

Mucinous but not clear cell histology is associated with inferior survival in patients with advanced stage ovarian carcinoma treated with platinum‐paclitaxel chemotherapy

Molecular typing of epithelial ovarian carcinomas using inflammatory markers

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