Detecting Estrogen Signatures in MCN Tumors via Targeted LC-MS/MS

A collaborative study between researchers in the United States and India has revealed that the stroma of pancreatic mucinous cystic neoplasm (MCN) tumors is not just a structural component but is functionally active, capable of producing estrogen and its metabolites. The team also demonstrated that a novel liquid chromatography–tandem mass spectrometry (LC-MS/MS) technique can reliably detect estrogen signatures in formalin-fixed, paraffin-embedded (FFPE) tissue samples—offering a new approach for studying hormone activity in archival tumor specimens. The findings were recently published in Frontiers in Cell and Developmental Biology (1).

A group of rare cystic tumors that may occur in the liver, pancreas, or retroperitoneum (2,3), MCNs occur almost exclusively in women, with a large proportion diagnosed as benign, and surgical excision offering an excellent prognosis (2,4). However, it has been noted that tumors of higher grade and larger size are more frequently encountered in older patients (2), lending support to the supposition that these tumors exist on a spectrum and will eventually progress from benign to malignant lesions (5). The exact mechanisms underlying this progression, however, are unknown (1).

Several theories have been postulated to explain the origin of these tumors. It has been suggested that the cysts may form due to the abundance of endodermally-derived epithelium and mesenchyme in response to the stimulation of female sex hormones. It has been proposed that these tumors may result from local hormone secretion by ectopic ovarian stroma derived from primordial ovarian cells deposited during embryological development (6,7).

MS coupled with GC or liquid chromatography (LC) has traditionally been used to identify and quantify endogenous estrogen and estrogen metabolites in biological samples (8). While other metabolites have been detected in FFPE tissue (9,10), the authors of the study report that there have been no previous reports describing the detection of estrogen and estrogen metabolites from FFPE samples using MS (1). For this study, they developed a targeted LC-MS/MS method to detect estrogen and estrogen metabolites from pancreatic tissue, capable of detecting estrogen metabolites at low femtomole levels (11-13).

The method was performed on 14 cases of MCN following macro dissection from formalin fixed tissue. The researchers identified that, relative to histologically normal pancreas, and intraductal papillary mucinous neoplasm (IPMN), the stroma in MCN expresses significantly greater levels of estrone (E1), estradiol (E2), estriol (E3), 2-hydroxyestradiol (2-OHE2), 2-methoxyestrone (2-MeOE1), 2-methoxyestradiol (2-MeOE2) and 16α-hydroxyestrone (16α-OHE1), at levels similar to those seen in the stroma in the normal ovary (1).

“These findings,” the authors wrote, “establish the functional capability of the ovarian-type stroma in MCN tumors for endogenous hormone production and show that the levels of estrogen in the stroma of MCN tumors approach those of the ovary. These findings serve as a basis for future studies examining the systemic effects of estrogen and the effects of estrogen on tumor progression, both in MCN tumors and tumor metastatic to the ovary.” (1)

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References

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