title: Morphoproteomic Characterization of Lung Squamous Cell Carcinoma Fragmentation, a Histological Marker of Increased Tumor Invasiveness.
abstract: Accurate stratification of tumors is imperative for adequate cancer management. In addition to staging, morphologic subtyping allows stratification of patients into additional prognostic groups. In this study, we used an image-based computational method on pan-cytokeratin IHC stainings to quantify tumor fragmentation (TF), a measure of tumor invasiveness of lung squamous cell carcinoma (LSCC). In two independent clinical cohorts from tissue microarrays (TMA:n= 208 patients) and whole sections (WS:n= 99 patients), TF was associated with poor prognosis and increased risk of blood vessel infiltration. A third cohort from The Cancer Genome Atlas (TCGA:n= 335 patients) confirmed the poor prognostic value of TF using a similar human-based score on hematoxylin-eosin staining. Integration of RNA-seq data from TCGA and LC-MS/MS proteomics from WS revealed an upregulation of extracellular matrix remodeling and focal adhesion processes in tumors with high TF, supporting their increased invasive potential. This proposed histologic parameter is an independent and unfavorable prognostic marker that could be established as a new grading parameter for LSCC.Cancer Res; 77(10); 2585-93. ©2017 AACR.
authors.affiliation: Institute of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland. ruben.casanova@usz.ch.
authors.forename: Ruben
authors.initials: R
authors.lastname: Casanova
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.|Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Daniel
authors.initials: D
authors.lastname: Xia
authors.affiliation: Institute of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Undine
authors.initials: U
authors.lastname: Rulle
authors.affiliation: Functional Genomics Center Zurich, University/ETH Zurich, Zurich, Switzerland.
authors.forename: Paolo
authors.initials: P
authors.lastname: Nanni
authors.affiliation: Functional Genomics Center Zurich, University/ETH Zurich, Zurich, Switzerland.
authors.forename: Jonas
authors.initials: J
authors.lastname: Grossmann
authors.affiliation: Institute of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Bart
authors.initials: B
authors.lastname: Vrugt
authors.affiliation: Department of Informatics, University of Zurich, Zurich, Switzerland.
authors.forename: Reto
authors.initials: R
authors.lastname: Wettstein
authors.affiliation: Department of Informatics, University of Zurich, Zurich, Switzerland.
authors.forename: Rafael
authors.initials: R
authors.lastname: Ballester-Ripoll
authors.affiliation: TOMCAT Beamline, Swiss Light Source, Paul Scherrer Institute, Villigen, Switzerland.
authors.forename: Alberto
authors.initials: A
authors.lastname: Astolfo
authors.affiliation: Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Walter
authors.initials: W
authors.lastname: Weder
authors.affiliation: Institute of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
authors.affiliation: TOMCAT Beamline, Swiss Light Source, Paul Scherrer Institute, Villigen, Switzerland.|Institute for Biomedical Engineering, University/ETH Zurich, Zurich, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Stampanoni
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School Boston, Massachusetts.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Beck
authors.affiliation: Institute of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Alex
authors.initials: A
authors.lastname: Soltermann
mesh_terms: D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D013058:Mass Spectrometry; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D040901:Proteomics / Q000379:methods; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor