Molecular Imaging of Endometriosis Tissues using Desorption Electrospray Ionization Mass Spectrometry

Feider, Clara L.; Woody, Spencer; Ledet, Suzanne; Zhang, Jialing; Sebastian, Katherine R.; Breen, Michael T.; Eberlin, Lívia S.

doi:10.1038/s41598-019-51853-y

Cited by 26 publications

(21 citation statements)

References 58 publications

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“…Furthermore, EMT of the ectopic endometrium might also be partially responsible at least for the diversity in the three entities. Similarly, Feider et al [ 112 ] and Guo [ 113 ] also mentioned that the differences between eutopic and ectopic endometrium might be due to their immediate environment rather than inherent differences between eutopic and ectopic endometrium. This does not exclude the possibility of inherited (somatic) mutations with additional genetic and epigenetic incidents in cystic ovarian endometriosis and DIE, as proposed by the genetic/epigenetic theory [ 26 ]; however, it remains unclear whether these changes occur preferentially in the endometrial epithelial or stromal cells.…”

Section: Discussionmentioning

confidence: 99%

Epithelial–Mesenchymal Transition in Endometriosis—When Does It Happen?

Konrad

Dietze

Riaz

et al. 2020

JCM

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Epithelial–mesenchymal transition (EMT) is an important process of cell remodeling characterized by the gradual loss of the epithelial phenotype and progressive gain of a mesenchymal phenotype. EMT is not an all-or-nothing process, but instead a transition of epithelial to mesenchymal cells with intermediate cell states. Recently, EMT was described in endometriosis, and many EMT-specific pathways like Twist, Snail, Slug, Zinc finger E-box-binding homeobox 1/2 (ZEB1/2), E/N-cadherin, keratins, and claudins are involved. However, as pointed out in this review, a comparison of the eutopic endometrium of women with and without endometriosis yielded only subtle changes of these EMT markers. Furthermore, only very few alterations in cell–cell contacts could be found but without changes in the epithelial phenotype. This suggests only a partial EMT which is not a prerequisite for the detachment of endometrial cells and, thus, not critical for the first step(s) in the pathogenesis of endometriosis. In contrast, the majority of changes in the EMT-related marker expression were found in the ectopic endometrium, especially in the three endometriotic entities, ovarian, peritoneal, and deep infiltrating endometriosis (DIE), compared with the eutopic endometrium. In this review, we examine the most important EMT pathways described in endometriosis and propose that partial EMT might result from the interaction of endometrial implants with their surrounding microenvironment.

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Section: Discussionmentioning

confidence: 99%

Epithelial–Mesenchymal Transition in Endometriosis—When Does It Happen?

Konrad

Dietze

Riaz

et al. 2020

JCM

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“…2, 4 and 5A ). This species had been previously described in ex vivo tissues as a heavy fluorinated compound (C 3 HF 6 SO 4 - ) of possible anesthetic origin (36). The detection of m/z 246.951 in the mass spectra collected intraoperatively provided evidence of the identification of this species as hexafluoroisopropyl sulfonate (HFIPS), a suspected secondary metabolite of sevoflurane, the anesthetic compound used during the surgical procedures.…”

Section: Resultsmentioning

confidence: 93%

Direct Molecular Analysis of In Vivo and Freshly Excised Tissues in Human Surgeries with the MasSpec Pen Technology

Zhang

Sans

et al. 2020

Preprint

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Intraoperative tissue analysis is critical to guide surgical procedures and improve patient outcomes. Here, we describe the clinical translation and intraoperative use of the MasSpec Pen technology for direct molecular analysis of in vivo and freshly excised tissues in the operating room. In this study, the MasSpec Pen was used by surgeons and surgical staff during 100 surgeries over a 12-month period, allowing rapid detection of rich mass spectral profiles from 715 in vivo and ex vivo analyses performed on thyroid, parathyroid, lymph node, breast, pancreatic, and bile duct tissues during parathyroidectomies, thyroidectomies, breast, and pancreatic neoplasia surgeries. The MasSpec Pen enabled gentle extraction and sensitive detection of various molecular species including small metabolites and lipids using a droplet of sterile water without causing apparent tissue damage. Notably, effective molecular analysis was achieved while no limitations to sequential histologic tissue analysis were identified and no device-related complications were reported for any of the patients. Collectively, this study shows that the MasSpec Pen system can be successfully incorporated into the operating room, allowing direct detection of rich molecular profiles from tissues with a seconds-long turnaround time that could be inform surgical and clinical decisions without disrupting tissue analysis workflows.

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“…We employed the Lasso method to build classification models for discriminating normal and PDAC based on a sparse set of m/z features characteristic of disease state (30). To maximize robustness of the Lasso model in detecting PDAC or normal pancreas, we used a training set of 78 tissue analyses with clear histologic regions of normal and tumor cells (>70%) within the area sampled.…”

Section: Resultsmentioning

confidence: 99%

Rapid diagnosis and tumor margin assessment during pancreatic cancer surgery with the MasSpec Pen technology

King

Zhang

Lin

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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Intraoperative delineation of tumor margins is critical for effective pancreatic cancer surgery. Yet, intraoperative frozen section analysis of tumor margins is a time-consuming and often challenging procedure that can yield confounding results due to histologic heterogeneity and tissue-processing artifacts. We have previously described the development of the MasSpec Pen technology as a handheld mass spectrometry–based device for nondestructive tissue analysis. Here, we evaluated the usefulness of the MasSpec Pen for intraoperative diagnosis of pancreatic ductal adenocarcinoma based on alterations in the metabolite and lipid profiles in in vivo and ex vivo tissues. We used the MasSpec Pen to analyze 157 banked human tissues, including pancreatic ductal adenocarcinoma, pancreatic, and bile duct tissues. Classification models generated from the molecular data yielded an overall agreement with pathology of 91.5%, sensitivity of 95.5%, and specificity of 89.7% for discriminating normal pancreas from cancer. We built a second classifier to distinguish bile duct from pancreatic cancer, achieving an overall accuracy of 95%, sensitivity of 92%, and specificity of 100%. We then translated the MasSpec Pen to the operative room and predicted on in vivo and ex vivo data acquired during 18 pancreatic surgeries, achieving 93.8% overall agreement with final postoperative pathology reports. Notably, when integrating banked tissue data with intraoperative data, an improved agreement of 100% was achieved. The result obtained demonstrate that the MasSpec Pen provides high predictive performance for tissue diagnosis and compatibility for intraoperative use, suggesting that the technology may be useful to guide surgical decision-making during pancreatic cancer surgeries.

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Molecular Imaging of Endometriosis Tissues using Desorption Electrospray Ionization Mass Spectrometry

Cited by 26 publications

References 58 publications

Epithelial–Mesenchymal Transition in Endometriosis—When Does It Happen?

Epithelial–Mesenchymal Transition in Endometriosis—When Does It Happen?

Direct Molecular Analysis of In Vivo and Freshly Excised Tissues in Human Surgeries with the MasSpec Pen Technology

Rapid diagnosis and tumor margin assessment during pancreatic cancer surgery with the MasSpec Pen technology

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