PMID- 28364001
OWN - NLM
STAT- MEDLINE
DCOM- 20170906
LR  - 20181219
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 77
IP  - 10
DP  - 2017 May 15
TI  - Morphoproteomic Characterization of Lung Squamous Cell Carcinoma Fragmentation, a 
      Histological Marker of Increased Tumor Invasiveness.
PG  - 2585-2593
LID - 10.1158/0008-5472.CAN-16-2363 [doi]
AB  - 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. (c)2017 AACR.
CI  - (c)2017 American Association for Cancer Research.
FAU - Casanova, Ruben
AU  - Casanova R
AD  - Institute of Pathology and Molecular Pathology, University Hospital Zurich, 
      Zurich, Switzerland. ruben.casanova@usz.ch.
FAU - Xia, Daniel
AU  - Xia D
AD  - Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
FAU - Rulle, Undine
AU  - Rulle U
AD  - Institute of Pathology and Molecular Pathology, University Hospital Zurich, 
      Zurich, Switzerland.
FAU - Nanni, Paolo
AU  - Nanni P
AD  - Functional Genomics Center Zurich, University/ETH Zurich, Zurich, Switzerland.
FAU - Grossmann, Jonas
AU  - Grossmann J
AD  - Functional Genomics Center Zurich, University/ETH Zurich, Zurich, Switzerland.
FAU - Vrugt, Bart
AU  - Vrugt B
AD  - Institute of Pathology and Molecular Pathology, University Hospital Zurich, 
      Zurich, Switzerland.
FAU - Wettstein, Reto
AU  - Wettstein R
AD  - Department of Informatics, University of Zurich, Zurich, Switzerland.
FAU - Ballester-Ripoll, Rafael
AU  - Ballester-Ripoll R
AD  - Department of Informatics, University of Zurich, Zurich, Switzerland.
FAU - Astolfo, Alberto
AU  - Astolfo A
AD  - TOMCAT Beamline, Swiss Light Source, Paul Scherrer Institute, Villigen, 
      Switzerland.
FAU - Weder, Walter
AU  - Weder W
AD  - Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.
FAU - Moch, Holger
AU  - Moch H
AD  - Institute of Pathology and Molecular Pathology, University Hospital Zurich, 
      Zurich, Switzerland.
FAU - Stampanoni, Marco
AU  - Stampanoni M
AD  - TOMCAT Beamline, Swiss Light Source, Paul Scherrer Institute, Villigen, 
      Switzerland.
AD  - Institute for Biomedical Engineering, University/ETH Zurich, Zurich, Switzerland.
FAU - Beck, Andrew H
AU  - Beck AH
AD  - Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical 
      School Boston, Massachusetts.
FAU - Soltermann, Alex
AU  - Soltermann A
AD  - Institute of Pathology and Molecular Pathology, University Hospital Zurich, 
      Zurich, Switzerland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170331
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Biomarkers, Tumor)
SB  - IM
EIN - Cancer Res. 2018 Feb 1;78(3):841. PMID: 29437123
MH  - *Biomarkers, Tumor
MH  - Carcinoma, Squamous Cell/*metabolism/mortality/*pathology
MH  - Extracellular Matrix/metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Kaplan-Meier Estimate
MH  - Lung Neoplasms/*metabolism/mortality/*pathology
MH  - Mass Spectrometry
MH  - Neoplasm Grading
MH  - Neoplasm Invasiveness
MH  - Neoplasm Staging
MH  - Prognosis
MH  - *Proteomics/methods
MH  - Retrospective Studies
EDAT- 2017/04/02 06:00
MHDA- 2017/09/07 06:00
CRDT- 2017/04/02 06:00
PHST- 2016/08/31 00:00 [received]
PHST- 2017/01/13 00:00 [revised]
PHST- 2017/03/08 00:00 [accepted]
PHST- 2017/04/02 06:00 [pubmed]
PHST- 2017/09/07 06:00 [medline]
PHST- 2017/04/02 06:00 [entrez]
AID - 0008-5472.CAN-16-2363 [pii]
AID - 10.1158/0008-5472.CAN-16-2363 [doi]
PST - ppublish
SO  - Cancer Res. 2017 May 15;77(10):2585-2593. doi: 10.1158/0008-5472.CAN-16-2363. 
      Epub 2017 Mar 31.