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Poster/ePoster Sessions
03. Endometrial cancer
#103 Epigenetic silencing of MLH1 as a prognostic factor for endometrial cancer recurrence
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  1. Tripac Irina1,
  2. Stratan Valentina1,
  3. Tutuianu Valeriu1,
  4. Sitnic Victor1,
  5. Calleja Agius Jean2,
  6. Vasileva-Slaveva Mariela3,
  7. Paul Kubelac4,
  8. Catalin Vlad4,
  9. Klejda Harasani5,
  10. Bucinskii Vladimir1 and
  11. Nino Japaridze6
  1. 1Institute of Oncology, Chisinau, Moldova
  2. 2University of Malta, Valetta, Malta
  3. 3Shterev Hospital, Sofia, Bulgaria
  4. 4Institute of Oncology „Prof. Dr. Ion Chiricuta’, Cluj-Napoca, Romania
  5. 5Medical University, Tirana, Albania
  6. 6Akaki Tsereteli State University, Kutaisi, Georgia

Abstract

Introduction/Background Aberrant DNA methylation is a common phenomenon in different types of cancer, but its patterns, causes, and consequences are poorly defined. Promoter hypermethylation of the DNA mismatch repair (MLH1) has been implicated in prognosis of endometrial cancer (EC).

Methodology Fifty women diagnosed with endometrioid-type endometrial adenocarcinoma from 2018–2021 at the Institute of Oncolgy of Moldova were included in this study. DNA was isolated from plasma, formalin-fixed, paraffin-embedded tumor. The methylation status of the MLH1 gene was determined using the Methylation specific Polymerase Chain Reaction (MS-PCR) method and specific primers for both unmethylated and methylated fragments. (figure 1).

Results Clinical and pathological characteristics for the 50 endometrial cancer patients are summarized in table 1. The mean age of the cohort was 59,9 ± 0,64 years (range, 39–87), and most of the patients had early stage (Stage I or II), grade 2 tumors with less than 50% myometrial invasion. The mean tumor size was 4,2 cm and the mean deapth of invasion 0,5cm. Myometrial lymphatic/vascular space and perineural invasion was present in nearly half the tumors and was much more common in stage II cases. Overall, 80% of the patients with EC had intact tumors, while 20% had hypermethylation of MLH1 (table 2). The presence of MLH1 epimutation was observed in 22.0% of EC patients in stage I and only in 2 patients in stage II.

Conclusion Recent developments in the field of epigenetics, especially studies of DNA methylation, have provided valuable insights for understanding the role of epigenetic alterations in normal cellular processes and abnormal changes leading to endometrial carcinogenesis. Promoter hypermethylation of MLH1 displayed a direct correlation with increasing age, poor differentiation of tumor, presense of myometral and limphovascular invasion. These phenotypes may underlie the different developmental pathways that are known to occur in endometrial cancer.

Abstract #103 Figure 1/Table 1, 2
Abstract #103 Figure 1/Table 1, 2

Disclosures None

https://doi.org/10.1136/ijgc-2023-ESGO.272

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