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

Bamias, Aristotle; Ψαλτοπούλου, Θεοδώρα; Sotiropoulou, Maria; Haidopoulos, Dimitrios; Lianos, Evangelos; Bournakis, Evangelos; Papadimitriou, Christos; Rodolakis, Alexandros; Vlahos, G.; Dimopoulos, Meletios Α.

doi:10.1002/cncr.24915

Cited by 80 publications

(56 citation statements)

References 19 publications

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“…EOC tumors are generally classified into histological subgroups depending on their aggressive behavior and their malignant potential (D'Andrilli et al 2008;Lalwani et al 2011). EOC classification becomes of interest during the planning of treatment and management as studies show that the different subtypes respond differently to treatment regimens (Bamias et al 2010). Further investigations into new predictive biomarkers that can identify subpopulations of patients who are most likely to respond to a given therapy should aid in EOC disease control.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, mucinous adenocarcinoma are considered to be refractory cancers that are biologically distinct from serous adenocarcinoma, and some studies suggest that mucinous tumors present a poorer outcome from platinum-based first-line chemotherapy when compared to non-mucinous epithelial ovarian cancers (Bamias et al 2010;Sugiyama et al 2009). …”

Section: Discussionmentioning

confidence: 99%

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Immunohistological Insight into the Correlation between Neuropilin-1 and Epithelial-Mesenchymal Transition Markers in Epithelial Ovarian Cancer

Adham

Al-Harrasi

Haddabi

et al. 2014

J Histochem Cytochem.

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The mechanism by which neuropilin-1 (NRP-1) induces malignancy in Epithelial Ovarian Cancer (EOC) is still unknown. This study is the first to demonstrate the relationship between NRP-1 expression and EMT markers vimentin, N-cadherin, E-cadherin and Slug. We used tissue microarrays containing the three main subtypes of EOC tumors: serous, mucinous cystadenocarcinoma and endometrioid adenocarcinoma and representative cases retrieved from our pathology archives. Immunohistochemistry was performed to detect the expression levels and location of NRP-1 and the aforementioned EMT proteins. NRP-1 was mainly expressed on cancer cells but not in normal ovarian surface epithelium (OSE). The Immunoreactive Scoring (IRS) values revealed that the expression of NRP-1, Slug and E-cadherin in the malignant subtypes of ovarian tissues was significantly higher (5.18 ± 0.64, 4.84 ± 0.7, 4.98 ± 0.68, respectively) than their expression in the normal and benign tissues (1.04 ± 0.29, 0.84 ± 0.68, 1.71 ± 0.66, respectively), with no significant differences among the studied subtypes. Vimentin was expressed in the cancer cell component of 43% of tumors and it was exclusively localized in the stroma of all mucinous tumors. The Spearman’s rho value indicated that NRP-1 is positively related to the EMT markers E-cadherin and Slug. This notion might indicate that NRP-1 is a partner in the EMT process in EOC tumors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Immunohistological Insight into the Correlation between Neuropilin-1 and Epithelial-Mesenchymal Transition Markers in Epithelial Ovarian Cancer

Adham

Al-Harrasi

Haddabi

et al. 2014

J Histochem Cytochem.

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“…However, advanced MAC has a poorer prognosis than other histopathologic subgroups (6). MAC's low response (26-42%) to conventional platinum-based chemotherapy is associated with a poor prognosis because chemosensitivity is one of the main prognostic factors for patients with advanced EOC (7)(8)(9)(10). Although MAC is known to be resistant to platinum/taxane combination chemotherapy (10), patients with MAC are usually treated with this first-line chemotherapy regimen.…”

Section: Discussionmentioning

confidence: 99%

“…Compared to serous adenocarcinoma (SAC), which is the most common histopathologic subgroup of EOC, MAC is relatively resistant to the conventional platinum or taxane-based chemotherapy, thereby leading to a poor prognosis (7)(8)(9)(10). It has been reported that MAC differs from SAC pathologically and cytogenetically, and more closely resembles colorectal cancer (11).…”

Section: Introductionmentioning

confidence: 99%

Cetuximab inhibits the growth of mucinous ovarian carcinoma tumor cells lacking KRAS gene mutations

Sato

Saga

Mizukami³

et al. 2012

Oncol Rep

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Abstract. The purpose of this study was to explore the possibility of targeted molecular therapy with anti-epidermal growth factor receptor (anti-EGFR) antibody (cetuximab) for the treatment of mucinous ovarian carcinoma. We analyzed EGFR protein expression and KRAS gene mutations in 5 mucinous ovarian carcinoma cell lines RMUG-L, RMUG-S, MN-1, OMC-1 and MCAS and evaluated the in vitro and in vivo effects of cetuximab on each. EGFR expression was observed in all cell lines except for MN-1 cells, and a KRAS gene mutation at codon 12 was detected only in the MCAS cell line. Cetuximab inhibited RMUG-L and OMC-1 cell growth in vitro and completely blocked RMUG-L tumor growth in vivo. On the other hand, cetuximab did not affect MCAS cell growth in vitro and only partially reduced the MCAS tumor growth in vivo. These results suggest the possibility of targeted molecular therapy with cetuximab for mucinous ovarian carcinoma cells lacking a KRAS gene mutation. IntroductionOvarian cancer is the fifth leading cause of cancer-relateddeath in the United States. Ovarian cancer was reported in ~22,000 women in 2010, ~14,000 of whom ultimately died of this disease (1). Since most patients with early-stage ovarian cancer seldom have symptoms, by the time they are diagnosed, >75% are already in the advanced stage (2). The standard treatment for ovarian cancer is cytoreductive surgery with platinum/taxane combination chemotherapy. Although ovarian cancer is generally sensitive to chemotherapy (3,4), there are cases that exhibit both natively drug-resistant tumors as well as tumors that eventually acquire drug tolerance. The 5-year survival rate is only 40% and has not improved in the last decade (1). Therefore, new strategies, especially targeted molecular therapy, require more attention in order to improve the prognosis of ovarian cancer.Mucinous ovarian adenocarcinoma (MAC) accounts for 10-14% of all types of epithelial ovarian cancers (EOC) (5,6). Compared to serous adenocarcinoma (SAC), which is the most common histopathologic subgroup of EOC, MAC is relatively resistant to the conventional platinum or taxane-based chemotherapy, thereby leading to a poor prognosis (7-10). It has been reported that MAC differs from SAC pathologically and cytogenetically, and more closely resembles colorectal cancer (11). These results suggest that therapeutic agents that are effective in treating colorectal cancer may also be effective for treating MAC.Epidermal growth factor (EGF) and its receptor (EGFR) are reportedly involved in the growth and extension of malignant tumors (12). In particular, EGFR overexpression has been observed in various malignant tumors (13). Further, EGFR overexpression has been reported to be a poor prognostic factor for various malignant tumors (14,15). It has been reported that EGFR is expressed in 48% of MAC tumors, and its expression is correlated with the histologic grade, stage and death rate (16).Cetuximab, an anti-EGFR monoclonal antibody, is a molecular-targeted therapeutic agent that was produced as a human...

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“…Certain histologic subtypes of epithelial ovarian cancer, such as mucinous and clear cell variants, have been suggested to demonstrate a chemoresistant phenotype [57,58]. A study based on a Japanese population-based cancer registry showed that in women older than 50 years, an increasing trend in clear cell, mucinous, and endometrioid adenocarcinomas was observed over a 24-year period from 1983 to 2007.…”

Section: More Aggressive Disease?mentioning

confidence: 99%

Doublet Chemotherapy in the Elderly Patient With Ovarian Cancer

Teo

Power

Tew³

et al. 2012

The Oncologist

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After completing this course, the reader will be able to:1. Summarize trends in the treatment of older women with ovarian cancer.2. Describe the potential value of performing a geriatric assessment prior to treatment in older women with ovarian cancer.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACTThe aging of the population has focused on the need to evaluate older patients with cancer. Approximately 50% of patients with ovarian cancer will be older than age 65 years. Increasing age has been associated with decreased survival. It is uncertain whether this relates to biologic factors, treatment factors, or both. There is concern that undertreatment may be associated with decreased survival. Older patients with ovarian cancer have been underrepresented in clinical trials. Therefore, the evidence base on which make decisions is lacking. Clinicians need to be aware of the currently available data to aid in treatment decisions. Doublet therapy is the most common standard treatment in epithelial ovarian cancer. It usually consists of a taxane and a platinum compound. A series of cooperative group studies in both the United States and Europe established intravenous paclitaxel and carboplatin as the most common standard in optimally debulked patients. The recent introduction of intraperitoneal therapy has complicated decision making in terms of which older patients would benefit from this more toxic therapy. In relapsed patients, the issue of platinum sensitivity is critical in deciding whether to reutilize platinum compounds. It is unclear whether single agents or combinations are superior, particularly in older patients. Geriatric assessment is an important component of decision making. Prospective studies are needed to develop strategies to determine the optimal treatment for older patients with ovarian cancer. The Oncologist

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

Cited by 80 publications

References 19 publications

Immunohistological Insight into the Correlation between Neuropilin-1 and Epithelial-Mesenchymal Transition Markers in Epithelial Ovarian Cancer

Immunohistological Insight into the Correlation between Neuropilin-1 and Epithelial-Mesenchymal Transition Markers in Epithelial Ovarian Cancer

Cetuximab inhibits the growth of mucinous ovarian carcinoma tumor cells lacking KRAS gene mutations

Doublet Chemotherapy in the Elderly Patient With Ovarian Cancer

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