Poster Presentation 31st Annual Lorne Proteomics Symposium 2026

Molecular Determinants of Lymph Node Metastasis in Endometrial Cancer: A Spatial Proteomics Investigation (#118)

Krisha H Chokshi 1 , Manuela Klingler-Hoffmann 1 , Parul Mittal 1 , Peter Hoffmann 1 , Martin Oehler 2
  1. University of South Australia, Adelaide , SA, Australia
  2. Department of Gynaecological Oncology, Royal Adelaide Hospital, Adelaide, SA, Australia

Endometrial cancer (EC) is the most prevalent gynaecological malignancy in developed countries and is the sixth most common cancer among women globally. Both incidence and mortality rates associated with this disease are increasing lymph node metastasis (LNM) is a critical prognostic factor, but current preoperative assessment techniques often lack the requisite sensitivity and specificity for accurate risk stratification. While only 10% of patients develop LNM, it remains standard practice for all patients to undergo lymph node (LN) dissection, which frequently results in chronic lymphedema. This complication adversely affects mobility and quality of life, which necessitates a new method to identify which patients require an LN dissection.

Our previous studies have shown that we can use matrix-assisted laser desorption/ ionisation mass spectrometry imaging (MALDI-MSI) to detect molecular markers that are specific to the LN status of the patient. Here, we have employed a deep visual proteomics (DVP) approach to the same cancer malignancy with different patient samples to gain a more detailed insight into the tumours. As part of this research, we have established laser capture microdissection (LMD) to precisely isolate tumour and stromal compartments, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis using a bottom -up proteomics approach. This approach has led to a significant increase in protein coverage from formalin-fixed and paraffin-embedded (FFPE) tissue and to the identification of additional molecular determinants of metastatic progression in EC.

The identified biomarkers and precursors will serve as potential tools for assessing the metastatic capability of primary tumours, enhancing the accuracy of preoperative risk assessments for LN metastasis, informing targeted treatment strategies, and optimising surgical planning. This may help minimise patient morbidity by reducing overtreatment and limiting invasive procedures.

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