Clinicopathological characteristics of mucinous adenocarcinoma of the ovary

Shimada, Muneaki; Kigawa, Junzo; Ohishi, Yoshihiro; Yasuda, Makoto; Suzuki, Mitsuaki; Hiura, Masamichi; Nishimura, Ryuichiro; Tabata, Tsutomu; Sugiyama, Toru; Kaku, Tsunehisa

doi:10.1016/j.ygyno.2009.02.010

Cited by 145 publications

(120 citation statements)

References 15 publications

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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%

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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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Section: Discussionmentioning

confidence: 99%

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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“…However, mEOC embodies a disease entity with a distinct natural history, molecular biology, chemo-sensitivity and prognosis in comparison with the predominant high-grade serous (HGSOC) subtype [6][7][8][9]. Alarmingly, the current gold standard of HGSOC chemotherapeutic management is still counterintuitively adopted for mEOC; a relatively chemoresistant disease [6][7][8]10]. Hence, within the burgeoning era of personalised medicine, there is an urge to pursue a more refined approach in systemically managing mEOC.…”

Section: Introductionmentioning

confidence: 99%

Mucinous ovarian cancer: A therapeutic review

Wen

Rush

Rickett

et al. 2016

Critical Reviews in Oncology/Hematology

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Highlights Mucinous epithelial ovarian cancer (mEOC) is a rare chemo-resistant subtype of ovarian cancer with distinct epidemiology, pathology and natural history.  mEOC can often masquerade as metastatic mucinous tumours from the gastrointestinal (GI) tract.  Molecularly, in contrast to high-grade serous ovarian cancer (HGSOC), mEOC are far less defined by p53 mutations and instead commonly harbour KRAS and HER 2 mutations.  The current gold standard of 1 st line platinum/taxane doublet chemotherapy, is more tailored towards HGSOC and generally ineffective for mEOC.  This review summarises the limited evidence for using GI style chemotherapeutic agents in treating mEOC and explores novel therapeutic possibilities such as targeting HER2, VEGF and Src. AbstractMucinous ovarian cancer represents approximately 3% of epithelial ovarian cancers (EOC).Despite this seemingly low prevalence, it remains a diagnostic and therapeutic conundrum that has resulted in numerous attempts to adopt novel strategies in managing this disease.Anecdotally, there has been a prevailing notion that established gold standard systemic regimens should be substituted for those utilised in cancers such as gastrointestinal (GI) malignancies; tumours that share more biological similarities than other EOC subtypes. This review summarises the plethora of small studies which have adopted this philosophy and influenced the design of the multinational GOG142 study, which was ultimately terminated due to poor accrual. To date, there is a paucity of evidence to support delivering 'GI style' chemotherapy for mucinous ovarian cancer over and above carboplatin-paclitaxel doublet therapy. Hence there is an urge to develop studies focused on targeted therapeutic agents driven by refined mutational analysis and conducted within the context of harmonised international collaborations.3

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“…However, clinical trials have been undertaken to improve prognosis. Since there are different clinical behavior patterns for certain histopathological subgroups, separate trials have been developed for clear cell (1) and mucinous carcinomas (2). The alteration of dose/schedule and the use of intraperitoneal therapy have been shown to be superior in at least one trial (3,4).…”

Section: Introductionmentioning

confidence: 99%

Cyclin D1 predicts the prognosis of advanced serous ovarian cancer

Hashimoto

Yanaihara

Okamoto

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. We previously reported that cyclin E (CCNE1) amplification is strongly associated with resistance to treatment in serous ovarian cancer by high-resolution oligonucleotide copy number analysis. Dysregulation of cell cycle control has been implicated as the key event in human oncogenesis, and aberrant expression of G1-S phase-related genes in particular has been reported in epithelial ovarian cancer (EOc). Nevertheless, there are conflicting results concerning the prognostic values of these abnormalities in EOC. This study focused on advanced serous EOC cases and investigated the association between the expression of G1-S phase-regulatory proteins and clinicopathological parameters. The utility of these proteins as prognostic factors was assessed, and whether these targets reflect chemoresistance of advanced serous EOC was investigated. A total of 66 patients treated by primary surgery were evaluated in this study. Immunohistochemical analysis for cyclin D1, pRb, p16, p53, p27 Kip1 , p21 Waf1/Cip1 and cyclin E was performed on formalin-fixed tissue sections collected from primary surgical specimens. The correlations between the expression of these proteins and the clinicopathological parameters, including progression-free survival (PFS), overall survival (OS) and chemosensitivity, were examined. Upon univariate analysis, overexpression of cyclin D1 was positively correlated with reduced PFS (p=0.00062) and OS (p=0.00037). Reduced expression of p27Kip1 was associated with shorter OS (p=0.064). Upon multivariate analysis, overexpression of cyclin D1 (p=0.0019), reduced expression of p27 Kip1 (p=0.042) and residual tumor volume (p=0.0092) were identified as independent predictors of OS. Overexpression of cyclin D1 (p=0.011) as well as residual tumor volume (p=0.006) were significantly associated with first-line chemosensitivity. In advanced serous EOC, overexpression of cyclin D1 contributed largely to poor prognosis, and this may have been in part mediated by chemoresistance. cyclin d1 is a possible target for overcoming the refractory nature of advanced serous EOc.

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Clinicopathological characteristics of mucinous adenocarcinoma of the ovary

Cited by 145 publications

References 15 publications

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

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

Mucinous ovarian cancer: A therapeutic review

Cyclin D1 predicts the prognosis of advanced serous ovarian cancer

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