Significant frequency of MSH2/MSH6 abnormality in ovarian endometrioid carcinoma supports histotype‐specific Lynch syndrome screening in ovarian carcinomas

Rambau, Peter; Duggan, Máire A.; Ghatage, Prafull; Warfa, Khadija; Steed, Helen; Perrier, Renee; Kelemen, Linda E.; Köbel, Martin

doi:10.1111/his.12934

Cited by 87 publications

(98 citation statements)

References 36 publications

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“…The study was approved by the local Ethics board (REB15-1124). Case ascertainment was previously described in detail [6]. Briefly, participants were identified from the Alberta cancer registry, an accredited population-based registry, which records and maintains data on all new carcinoma patients and carcinoma deaths occurring within Alberta, Canada.…”

Section: Methodsmentioning

confidence: 99%

“…Triplicate 0.6 mm tissue microarrays (TMA) were previously constructed [6], including normal tissue (tonsil, placenta, kidney, liver, and pancreas) as a control. Formalin fixed, paraffin embedded 4 µm TMA sections were deparaffinized and rehydrated.…”

Section: Methodsmentioning

confidence: 99%

“…EC harbors mutations in CTNNB1 , PIK3CA , KRAS , ARID1A , PTEN , PPR2R1A but uncommonly in TP53 (less than 15%) [4]. Mismatch repair protein expression is deficient in 10%–13% of cases [5,6]. WT1 expression is typically absent in EC (although expressed in up to 10% of cases).…”

Section: Introductionmentioning

confidence: 99%

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Association of Hormone Receptor Expression with Survival in Ovarian Endometrioid Carcinoma: Biological Validation and Clinical Implications

Rambau

Kelemen

Steed

et al. 2017

IJMS

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This paper aims to validate whether hormone receptor expression is associated with longer survival among women diagnosed with ovarian endometrioid carcinoma (EC), and whether it identifies patients with stage IC/II tumors with excellent outcome that could be spared from toxic chemotherapy. Expression of estrogen receptor (ER) and progesterone receptor (PR) was assessed on 182 EC samples represented on tissue microarrays using the Alberta Ovarian Tumor Type (AOVT) cohort. Statistical analyses were performed to test for associations with ovarian cancer specific survival. ER or PR expression was present in 87.3% and 86.7% of cases, respectively, with co-expression present in 83.0%. Expression of each of the hormonal receptors was significantly higher in low-grade tumors and tumors with squamous differentiation. Expression of ER (Hazard Ratio (HR) = 0.18, 95% confidence interval 0.08–0.42, p = 0.0002) and of PR (HR = 0.22, 95% confidence interval 0.10–0.53, p = 0.0011) were significantly associated with longer ovarian cancer specific survival adjusted for age, grade, treatment center, stage, and residual disease. However, the five-year ovarian cancer specific survival among women with ER positive stage IC/II EC was 89.0% (standard error 3.3%) and for PR positive tumors 89.9% (standard error 3.2%), robustly below the 95% threshold where adjuvant therapy could be avoided. We validated the association of hormone receptor expression with ovarian cancer specific survival independent of standard predictors in an independent sample set of EC. The high ER/PR co-expression frequency and the survival difference support further testing of the efficacy of hormonal therapy in hormone receptor-positive ovarian EC. The clinical utility to identify a group of women diagnosed with EC at stage IC/II that could be spared from adjuvant therapy is limited.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Association of Hormone Receptor Expression with Survival in Ovarian Endometrioid Carcinoma: Biological Validation and Clinical Implications

Rambau

Kelemen

Steed

et al. 2017

IJMS

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“…Beim Lynch-Syndrom scheinen Mammakarzinome nicht gehäuft vorzukommen. Ovarialkarzinome, speziell vom klarzelligen und endometrioiden Typ, finden sich hingegen im Rahmen des Spektrums der Lynchassoziierten Tumoren [16,24].…”

Section: Mamma-und Ovarialkarzinome Im Rahmen Weiterer Hereditärer Tuunclassified

Familiäres Mamma- und Ovarialkarzinom

Lax¹

2017

Pathologe

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“…In recent years it has been appreciated that patients with Lynch syndrome (LS), due to germline mutations in genes encoding for the DNA mismatch repair (MMR) proteins MLH1, PMS2, MSH2 or MSH6 have an increased risk (approximately 10%) of developing ovarian neoplasia and the majority of these tumours are ECs or CCCs . Therefore, reflex immunohistochemistry for MMR proteins has been proposed in these cases …”

Section: Introductionmentioning

confidence: 99%

Long‐term survival of patients with mismatch repair protein‐deficient, high‐stage ovarian clear cell carcinoma

et al. 2016

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Significant frequency of MSH2/MSH6 abnormality in ovarian endometrioid carcinoma supports histotype‐specific Lynch syndrome screening in ovarian carcinomas

Abstract: Our data support the policy of histotype-specific Lynch syndrome screening in ovarian carcinoma confined to endometrioid and clear cell carcinomas.

Cited by 87 publications

References 36 publications

Association of Hormone Receptor Expression with Survival in Ovarian Endometrioid Carcinoma: Biological Validation and Clinical Implications

Association of Hormone Receptor Expression with Survival in Ovarian Endometrioid Carcinoma: Biological Validation and Clinical Implications

Familiäres Mamma- und Ovarialkarzinom

Long‐term survival of patients with mismatch repair protein‐deficient, high‐stage ovarian clear cell carcinoma

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