Immunohistochemical expression of mismatch repair proteins (MSH2, MSH6, MLH1, and PMS2) in prostate cancer: correlation with grade groups (WHO 2016) and ERG and PTEN status

Albero-González, Raquel; Hernández‐Llodrà, Silvia; Juanpere, Núria; Lorenzo, Marta; Lloret, A. Corbera; Segalés, Laura; Duran, Xavier; Fumadó, Lluís; Cecchini, L.; Lloreta‐Trull, Josep

doi:10.1007/s00428-019-02591-z

Cited by 23 publications

(43 citation statements)

References 41 publications

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“…In many cancers, mismatch repair proteins are overexpressed 53–55 . In Prostate cancer, there are studies which indicate that Msh6overexpression contributes to aggressiveness of the cancer 54,56 . Additionally, mutational signatures in prostate cancer are dominated by GC to AT transition mutations 57 .…”

Section: Discussionmentioning

confidence: 99%

Overexpression of MutS impairs DNA mismatch repair and causes cell division defect inE.coli

Iyer

Moharir

Kumar

2020

Preprint

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MutS and its homologues, from prokaryotes to humans, recognize and bind to DNA mismatches generated during DNA replication, initiate DNA mismatch repair and ensures 100-200 fold increase in replication fidelity. In E.coli, through post transcriptional regulation, at least three mechanisms mediate decline of MutS intracellular concentrations during stress conditions. To understand the significance of this multifold regulation, we overexpressed MutS in E.coli and found that it led to impairment of DNA mismatch repair as reflected by preferential accumulation of transition mutations in spontaneous base pair substitution spectrum. This phenomenon was dependent on MutS-mismatch affinity and interaction. Higher MutS overexpression levels promoted DNA double strand breaks, inhibited cell division and resultantly caused a manifold increase in E.coli cell length. This cell division defect involved a novel MutS-FtsZ interaction and impediment of FtsZ ring function. Our findings may have relevance for cancers where mismatch proteins are known to be overexpressed.

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Section: Discussionmentioning

confidence: 99%

Overexpression of MutS impairs DNA mismatch repair and causes cell division defect inE.coli

Iyer

Moharir

Kumar

2020

Preprint

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“…ETS ailesinde 28'i insan genomunda da tanımlanmış 30 adet gen vardır. Bu aileyle ilişkili onkogen olarak bilinen ERG, farklı tümörlerde bazı füzyonlar sonucu yeni onkogenik proteinler oluşturma potansiyeline sahiptir (5,19) . Günümüzde ERG ile ilişkili en çok çalışılan tümörlerden biri prostat adenokarsinomudur.…”

Section: Discussionunclassified

“…Prostat adenokarsinomlarının yarısından çoğunda ERG ile androjen regüle edici gen transmembran proteazı, serin 2 (TMPSSR2) arasında füzyon mevcuttur (6,7) . ERG füzyon proteininin, prostatta erken kök hücrelerde matürasyonu durdurduğu ve karsinogenezi başlattığı düşünülmektedir (19) . ERG füzyonu prostat adenokarsinomunda ilk olarak 2005 yılında Tomlins ve ark.…”

Section: Discussionunclassified

“…Farklı çalışmalarda, immunohistokimyasal ERG pozitifliği prostat adenokarsinomlarında %10 ile %68 arasında bildirilmiştir (6,7) . Çalışmalarda, ERG ekspresyonu genellikle immünohistokimyasal olarak incelense de, bazı araştırmacılar FISH ve PCR gibi yöntemleri kullanmışlardır (11,19) . ERG ekspresyon oranlarındaki bu değişkenliğin seçilen ERG saptama yöntemlerinin arasındaki farklılığa bağlı olduğu düşünülebilir.…”

Section: Discussionunclassified

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Evaluation of Immunhistochemical ERG Tissue Expression in Wilms Tumor

Dınız¹,

Birol²,

Öniz³

et al. 2020

BUCH

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Objective: The ETS-related gene (ERG) is an oncogene that encodes one of the erythroblast transformationspecific (ETS) transcription factors. Although there are many studies on their effects on the development of different malignancies, mainly prostate cancer, Ewing sarcoma and acute myeloid leukemia, its association with Wilms tumor has never been investigated. The aim of this study was to evaluate ERG tissue expression in Wilms tumors. Methods: ERG expression and its association with clinicopathological features were evaluated in tissue sections obtained from 53 children with Wilms tumors. Results: The mean age of the cases was 3.21±2 years. This series consisted of 25 boys (47.2%) and 28 girls (52.8%). The mean tumor size was 9.1±2.9 cm. The mean kidney weight was 474.5±310.7 g. Thirteen (24.5%) cases were in stage I, 20 (37.7%) in stage II, 7 (14%) in stage III and 6 (11.3%) in stage IV. Forty-two cases were alive (79.2%) and being followed up. The mean survival time was 65.3±40.2 (2-148) months. Nuclear ERG expression was detected in 21 (39.6%) cases. In 8 (15.1%) cases, ERG expression was limited to pure blastemal component. Eleven cases (20.8%) had ERG expression in blastemal and mesenchymal components. Two patients (3.8%), one of which with bilateral tumors, had diffuse nuclear ERG expression. There was no correlation between ERG expression and prognostic factors except tumor bilaterality. Conclusion: This study demonstrates that nuclear ERG expression is not related to the pathogenesis of Wilms tumor. Although there was no statistically significant p value; since ERG expression is more common in bilateral tumors, it is thought that ERG may have a supporting role in the development of WT.

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“…In prostate cancer, dMMR most commonly occurs due to loss of expression of MSH2, variably associated with MSH6 loss of expression. 84 Importantly, loss of expression can be heterogeneous 85 but the impact of this heterogeneity on response to ICI has not yet been investigated (Fig. 6).…”

Section: Homologous Recombination Dna Repair Deficiencymentioning

confidence: 99%

Molecular pathology of prostate cancer: a practical approach

Vlajnic

Bubendorf

2021

Pathology

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While localised prostate cancer can be cured by local treatment, 'high-risk' prostate cancer often progresses to castration resistant disease and remains incurable with a dismal prognosis. In recent years, technical advances and development of novel methodologies have largely contributed to a better understanding of underlying molecular mechanisms that promote tumour growth and progression. Consecutively, novel therapeutic strategies for treatment of prostate cancer have emerged during the last decade, calling for the identification of predictive biomarkers. The concept of personalised medicine is to tailor treatment according to the specific tumour profile of an individual patient. Moreover, acquired molecular changes during tumour evolution and in response to therapy selection pressure require adapted predictive marker testing at different time points during the disease. In this setting, the pathologist plays a critical role in patient management and treatment selection. In this review, we provide a comprehensive overview of the current knowledge of molecular aspects of prostate cancer and their potential utility in the context of different therapeutic approaches. Furthermore, we discuss methods for molecular marker testing in routine clinical practice, with a focus on castration resistant prostate cancer.

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Immunohistochemical expression of mismatch repair proteins (MSH2, MSH6, MLH1, and PMS2) in prostate cancer: correlation with grade groups (WHO 2016) and ERG and PTEN status

Cited by 23 publications

References 41 publications

Overexpression of MutS impairs DNA mismatch repair and causes cell division defect inE.coli

Overexpression of MutS impairs DNA mismatch repair and causes cell division defect inE.coli

Evaluation of Immunhistochemical ERG Tissue Expression in Wilms Tumor

Molecular pathology of prostate cancer: a practical approach

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