ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
This article is part of the Research TopicAdvances in Gastrointestinal CancersView all 6 articles
Mucinous Cystic Neoplasms of The Pancreas Demonstrate In-Situ Production of Estrogen
Provisionally accepted
Aswath Chandrasekar1*
Jinyong Kim1
Benjamin J. Van Treeck1Maria C. Olave1
Maryam Shahi1Roger K. Moreira1Seul Kee Byeon1Gunveen S. Sachdeva1Justin E. Juskewitch1Jamie N. Bakkum-Gamez1
Scott H. Kaufmann1Sun-Hee Lee1Michelle D. Reid2Maria Westerhoff3Daniela S. Allende4
Akhilesh Pandey1
Rondell Graham1- 1Mayo Clinic, Rochester, United States
- 2Emory University Hospital, Atlanta, United States
- 3University of Michigan, Ann Arbor, United States
- 4Cleveland Clinic, Cleveland, United States
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Mucinous cystic neoplasms (MCNs) are rare cystic tumors that may occur in the liver, pancreas, or retroperitoneum, defined histologically by the presence of an "ovarian type stroma." While this morphology has been well characterized, it remains unknown whether the tumor stroma is functionally active. In our current study, we describe the detection of estrogen and its metabolites in the ovarian-type stroma of MCN tumors of the pancreas, using a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique. We performed LC-MS/MS on 14 cases of MCN, with and without dysplasia, following macro dissection from formalin fixed tissue, and 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. These findings establish the functional capability of the ovarian type of stroma in MCN tumors in endogenous hormone production and establish that the levels of estrogen in the stroma of MCN tumors approaches that 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 in tumor metastatic to the ovary.
Keywords: Pancraetic cancer, estrogen, Tumor Microenvironment, Mass Spectromelry, Tumor biology
Received: 12 Aug 2025; Accepted: 28 Oct 2025.
Copyright: © 2025 Chandrasekar, Kim, Van Treeck, Olave, Shahi, Moreira, Byeon, Sachdeva, Juskewitch, Bakkum-Gamez, Kaufmann, Lee, Reid, Westerhoff, Allende, Pandey and Graham. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Aswath Chandrasekar, apadmanabhanchandrasekar@bwh.harvard.edu
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