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dc.contributor.authorShiraishi, Takehiro
dc.contributor.authorShinto, Eiji
dc.contributor.authorNearchou, Ines P
dc.contributor.authorTsuda, Hitoshi
dc.contributor.authorKajiwara, Yoshiki
dc.contributor.authorEinama, Takahiro
dc.contributor.authorCaie, Peter D
dc.contributor.authorKishi, Yoji
dc.contributor.authorUeno, Hideki
dc.identifier.citationShiraishi , T , Shinto , E , Nearchou , I P , Tsuda , H , Kajiwara , Y , Einama , T , Caie , P D , Kishi , Y & Ueno , H 2020 , ' Prognostic significance of mesothelin expression in colorectal cancer disclosed by area-specific four-point tissue microarrays ' , Virchows Archiv , vol. First Online .
dc.identifier.otherPURE: 266677894
dc.identifier.otherPURE UUID: 5b22e8f6-f2e3-4faf-9dda-d2b583380621
dc.identifier.otherPubMed: 32107600
dc.identifier.otherORCID: /0000-0002-0031-9850/work/70234019
dc.identifier.otherScopus: 85080133384
dc.identifier.otherORCID: /0000-0002-1863-5413/work/75610529
dc.identifier.otherWOS: 000518134600001
dc.descriptionI.P.N. is the recipient of a Medical Research Scotland PhD Studentship awarded to P.D.C.en
dc.description.abstractMesothelin (MSLN) is a cell surface glycoprotein present in many cancer types. Its expression is generally associated with an unfavorable prognosis. This study examined the prognostic significance of MSLN expression in different areas of individual colorectal cancers (CRCs) using tissue microarrays (TMAs) by enrolling 314 patients with stage II (T3-T4, N0, M0) CRCs. Using formalin-fixed paraffin-embedded tissue blocks from patients, TMA blocks were constructed. Tissue core specimens were obtained from submucosal invasive front (Fr-sm), subserosal invasive front (Fr-ss), central area (Ce), and rolled edge (Ro) of each tumor. Using these four-point TMA sets, MSLN expression was immunohistochemically surveyed. The area-specific prognostic significance of MSLN expression was evaluated. A deep learning convolutional neural network algorithm was used for imaging analysis and evaluating our judgment's objectivity. MSLN staining ratio was positively correlated between the manual and machine-learning analyses (r = 0.71). The correlation coefficient between Ro and Ce, Ro and Fr-sm, and Ro and Fr-ss was r = 0.63, r = 0.54, and r = 0.61, respectively. Disease-specific survival curves for the MSLN-positive and MSLN-negative groups in Fr-sm, Fr-ss, and Ro were significantly different (five-year survival rates 88.1% and 95.5% (P = 0.024), 85.0 and 96.2% (P = 0.0087), 87.8 and 95.5% (P = 0.051), and 77.9 and 95.8% (P = 0.046) for Fr-sm, Fr-ss, Ce, and Ro, respectively). The analysis performed using area-specific four-point TMAs clearly demonstrated that MSLN expression in stage II CRC was relatively homogeneous within tumors. Additionally, high MSLN expression showed or tended to show unfavorable prognostic significance regardless of the tumor area.
dc.relation.ispartofVirchows Archiven
dc.rightsCopyright © 2020 Springer-Verlag GmbH Germany, part of Springer Nature. This work has been made available online in accordance with publisher policies or with permission. Permission for further reuse of this content should be sought from the publisher or the rights holder. This is the author created accepted manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at
dc.subjectColorectal canceren
dc.subjectTissue microarrayen
dc.subjectArtificial intelligenceen
dc.subjectDeep learningen
dc.subjectQA75 Electronic computers. Computer scienceen
dc.subjectRB Pathologyen
dc.subjectRC0254 Neoplasms. Tumors. Oncology (including Cancer)en
dc.titlePrognostic significance of mesothelin expression in colorectal cancer disclosed by area-specific four-point tissue microarraysen
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.contributor.institutionUniversity of St Andrews.Cellular Medicine Divisionen
dc.contributor.institutionUniversity of St Andrews.Sir James Mackenzie Institute for Early Diagnosisen
dc.contributor.institutionUniversity of St Andrews.Centre for Biophotonicsen
dc.description.statusPeer revieweden

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