Endometrial cancer constitutes the most prevalent gynaecological malignancy in developed countries and ranks as the sixth most common cancer among women globally. Both incidence and mortality rates associated with this disease are on the rise. Lymph node (LN) metastasis is a critical prognostic factor; however, current preoperative assessment techniques often lack the requisite sensitivity and specificity for accurate risk stratification. While only 10% of patients develop LN metastasis, it remains standard practice for all patients to undergo LN dissection, which frequently results in chronic lymphedema. This complication adversely affects mobility and quality of life, highlighting the limitations of existing preoperative assessment methodologies.
Our previous studies have shown that we can use Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) to detect molecular markers which are specific to the lymph node status of the patient. Here, we are employing a deep visual proteomics approach to the same tissue to gain a more detailed insight into the tumours. As part of this research, we have established Laser Capture Microdissection (LCM) to precisely isolate tumour and stromal compartments, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. This approach has led to a significant increase in protein coverage from FFPE tissue and to the identification of additional molecular determinants of metastatic progression.
The identified biomarkers and precursors will serve as essential 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.