hMLH1 promoter hypermethylation and MSI status in human endometrial carcinomas with and without metastases.

Clinical & Experimental Metastasis
J BischoffR Schneider-Stock

Abstract

We investigated the methylation status of mismatch repair gene hMLH1 in 80 primary human endometrial carcinomas (ECs) and in 30 metastatic lesions. It was correlated to the expression of hMLH1 protein, microsatellite instability (MSI) of ECs and to the well-known clinico-pathological variables of cancer. The hMLH1 promoter methylation was detected in 24 out of 64 (37.5 %) primary ECs but only in one out of 18 (5.6 %) metastatic lesions investigated. Promoter hMLH1 hypermethylation was found more often in early stage ECs and was associated with a decrease of hMLH1 protein expression immunohistochemically. An inverse relationship between hMLH1 expression and clinical stage of the disease was found (p = 0.048). Interestingly, there was a significant correlation between MSI and hMLH1 protein expression level (p = 0.042). MSI phenotype was found more often in EC metastases compared to the primary tumors (66.7 % vs 29.3 %; p = 0.039). However, neither hMLH1 promoter hypermethylation nor MSI was independent predictive factors for patient's outcome. Using an in vitro model we showed that hMLH1 methylation is reversible. These data showed that hMLH1 methylation with a consequent protein decrease occurred early during EC tumorigenesis an...Continue Reading

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Citations

Jul 23, 2013·International Journal of Molecular Sciences·Yannick DelpuJérôme Torrisani
Jul 3, 2013·BioMed Research International·Peixin DongNoriaki Sakuragi
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May 5, 2017·Epigenomics·Carla BartoschCarmen Jerónimo
Jan 23, 2019·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Tsutomu Miyamoto, Tanri Shiozawa
Oct 24, 2019·Cell Death & Disease·Sukaina RashidSarah A Martin
Aug 28, 2020·Frontiers in Oncology·Joshua T BurgessEmma Bolderson
Nov 29, 2017·Molecular and Clinical Oncology·Megumi YanokuraDaisuke Aoki

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