Molecular abnormalities in ovarian carcinoma: clinical, morphological and therapeutic correlates

Gurung, Ananta; Hung, Tawny; Morin, Jason; Gilks, C Blake

doi:10.1111/his.12033

Cited by 95 publications

(96 citation statements)

References 104 publications

(113 reference statements)

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“…Diagnosis therefore implies exhaustive sampling. The most common molecular alterations are KRAS mutations, occurring in 75% of primary MC; these have been identified in benign and in borderline areas as well as in adjacent carcinomas, supporting the sequential tumorigenesis process going from a low-grade malignant mucinous lesion to an MC [5,[33][34][35][36]. HER2 amplification is also found in around 20% of MC.…”

Section: Mucinous Carcinomasmentioning

confidence: 99%

Ovarian Cancer: A Heterogeneous Disease

Kossaï¹,

Leary²,

Scoazec³

et al. 2017

Pathobiology

264

204

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Ovarian cancer encompasses a collection of neoplasms with distinct clinicopathological and molecular features and prognosis. Despite there being a variety of ovarian cancer subtypes, these are treated as a single disease. Tremendous efforts have been made to characterize these subtypes and identify tumoral pathways and potential biomarkers for therapeutic strategies. As in other cancer types, tumor heterogeneity appears to be very high across subtypes and within a single tumor, representing a major cause of treatment failure. We describe the morphological and molecular heterogeneity among ovarian cancers and discuss recent advances in our understanding of intratumor heterogeneity.

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Section: Mucinous Carcinomasmentioning

confidence: 99%

Ovarian Cancer: A Heterogeneous Disease

Kossaï¹,

Leary²,

Scoazec³

et al. 2017

Pathobiology

264

204

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“…Pathologically, EOC is broadly classified as serous or non-serous histology. Each subtype has distinct clinical characteristics and is associated with different genetic risk factors and molecular events [3,4]. Therefore, understanding of molecular mechanisms of EOC is crucial to the treatment of ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

Crk-like adapter protein regulates CCL19/CCR7-mediated epithelial-to-mesenchymal transition via ERK signaling pathway in epithelial ovarian carcinomas

et al. 2015

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Recent studies have suggested that Crk-like adapter protein (CrkL) and epithelial-to-mesenchymal transition (EMT) induced by CCL19/CCR7 play an important role in ovarian epithelial carcinogenesis. However, the regulatory mechanisms of CrkL on the CCL19/CCR7 signaling pathways in epithelial ovarian carcinomas (EOC) are not well characterized. Here, CCR7 and CrkL proteins were tested in 30 EOC tissues and cell lines. In vitro, the roles of CrkL in CCL19-stimulated SKOV-3 cell invasion and migration were investigated. In this work, CCR7 and CrkL over-expressed in EOC tissues and cell lines and correlated with FIGO stage and lymph node metastasis. Moreover, CCR7 and CrkL serve as an independent prognostic factor. In SKOV-3 cells, CrkL knockdown markedly suppressed the CCL19-stimulated expression of p-ERK and EMT biomarkers (N-cadherin, Snail and MMP9), compared with control. In contrast, p-AKT expression level did not change. On the other hand, functional analysis revealed CrkL knockdown could significantly decrease SKOV-3 cell invasion number of transwell invasion assay, and wound closure area of wound healing assay, compared to control. In conclusion, CrkL regulates CCL19/CCR7-induced EMT via ERK signaling pathway in EOC patients, which further suggested CrkL could be suggested as an efficient target in ovarian cancer treatment.

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“…The EOC were classified into borderline and invasive EOC. We grouped the iEOC into Type I (low‐grade serous, low/moderate‐grade endometrioid, clear cell and mucinous cancers) and Type II [moderate/high‐grade serous, high‐grade endometrioid, undifferentiated, malignant mixed mesodermal (carcinosarcomas)] cancers 22, 23. Borderline tumours with their excellent survival rates, younger age of onset, differing risk factors and favourable response to surgery were assessed separately from iEOC.…”

Section: Introductionmentioning

confidence: 99%

Time to diagnosis of Type I or II invasive epithelial ovarian cancers: a multicentre observational study using patient questionnaire and primary care records

Lim

Mesher

Gentry‐Maharaj

et al. 2015

BJOG

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ObjectiveTo compare time to diagnosis of the typically slow‐growing Type I (low‐grade serous, low‐grade endometrioid, mucinous, clear cell) and the more aggressive Type II (high‐grade serous, high‐grade endometrioid, undifferentiated, carcinosarcoma) invasive epithelial ovarian cancer (iEOC).DesignMulticentre observational study.SettingTen UK gynaecological oncology centres.PopulationWomen diagnosed with primary EOC between 2006 and 2008.MethodsSymptom data were collected before diagnosis using patient questionnaire and primary‐care records. We estimated patient interval (first symptom to presentation) using questionnaire data and diagnostic interval (presentation to diagnosis) using primary‐care records. We considered the impact of first symptom, referral and stage on intervals for Type I and Type II iEOC.Main outcome measuresPatient and diagnostic intervals.ResultsIn all, 78% of 60 Type I and 21% of 134 Type II iEOC were early‐stage. Intervals were comparable and independent of stage [e.g. median patient interval for Type I: early‐stage 0.3 months (interquartile range 0.3–3.0) versus late‐stage 0.3 months (interquartile range 0.3–4.5), P = 0.8]. Twenty‐seven percent of women with Type I and Type II had diagnostic intervals of at least 9 months. First symptom (questionnaire) was also similar, except for the infrequent abnormal bleeding (Type I 15% versus Type II 4%, P = 0.01). More women with Type I disease (57% versus 41%, P = 0.04) had been referred for suspected gynaecological cancer. Median time from referral to diagnosis was 1.4 months for women with iEOC referred via a 2‐week cancer referral to any specialty compared with 2.6 months (interquartile range 2.0–3.7) for women who were referred routinely to gynaecology.ConclusionOverall, shorter diagnostic delays were seen when a cancer was suspected, even if the primary tumour site was not recognised to be ovarian. Despite differences in carcinogenesis and stage for Type I and Type II iEOC, time to diagnosis and symptoms were similar. Referral patterns were different, implying subtle symptom differences. If symptom‐based interventions are to impact on ovarian cancer survival, it is likely to be through reduced volume rather than stage‐shift. Further research on histological subtypes is needed.Tweetable abstractNo difference in time to diagnosis for Type I versus Type II invasive epithelial ovarian cancers.

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Molecular abnormalities in ovarian carcinoma: clinical, morphological and therapeutic correlates

Cited by 95 publications

References 104 publications

Ovarian Cancer: A Heterogeneous Disease

Ovarian Cancer: A Heterogeneous Disease

Crk-like adapter protein regulates CCL19/CCR7-mediated epithelial-to-mesenchymal transition via ERK signaling pathway in epithelial ovarian carcinomas

Time to diagnosis of Type I or II invasive epithelial ovarian cancers: a multicentre observational study using patient questionnaire and primary care records

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