MutL homolog 1 promoter hypermethylation (MLH1ph) is a molecular marker that identifies a distinct, higher-risk subgroup in endometrial cancer (EC), according to a recent study published in Gynecologic Oncology.
Around 30% of ECs are mismatch repair deficient (MMRd), meaning the cancer cells have mutations in genes that are involved in correcting DNA copying errors. MLH1ph ECs are a subgroup that involve mutations to the MLH1 gene, which makes a protein that aids in DNA repair. Around 14% of ECs are MLH1ph.
Previous studies have suggested that MLH1ph ECs could be more aggressive than other MMRd ECs, though findings on survival outcomes have been inconsistent. To better understand MLH1ph ECs, the authors performed a meta-analysis, a type of study that pools the results of several smaller studies on a given subject to examine the validity of a hypothesis.
Using data from almost 4,000 patients across multiple cohort studies and clinical trials, the analysis revealed that patients with MLH1ph ECs had significantly poorer overall survival (OS) and progression-free survival (PFS), with around 35% higher risk of death and almost 34% higher risk of progression or death compared to non-MLH1ph MMRd ECs.
The results also showed that MLH1ph ECs have worse prognostic features, including advanced stage and lymphovascular space invasion. They showed reduced response to platinum-based chemotherapy, the standard of care for advanced stage EC.
Read more about EC treatment and care
These findings highlight MLH1ph as a distinct, high-risk subgroup, underscoring the need for targeted testing and more personalized treatment strategies for patients with MLH1ph EC.
“MLH1ph ECs represent a higher-risk molecular subgroup with significantly poorer survival,” the authors wrote. “Patients may require more frequent surveillance to detect recurrence early, as well as tailored management strategies to mitigate increased risk of disease progression.”
Sign up here to get the latest news, perspectives, and information about EC sent directly to your inbox. Registration is free and only takes a minute.
