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Morphoproteomic characterization of lung squamous cell carcinoma fragmentation, a histological marker of increased tumor invasiveness


Casanova, Ruben; Xia, Daniel; Rulle, Undīne; Nanni, Paolo; Grossmann, Jonas; Vrugt, Bart; Wettstein, Reto; Ballester, Rafael; Astolfo, Alberto; Weder, Walter; Moch, Holger; Stampanoni, Marco; Beck, Andrew H; Soltermann, Alex (2017). Morphoproteomic characterization of lung squamous cell carcinoma fragmentation, a histological marker of increased tumor invasiveness. Cancer Research, 77(10):2585-2593.

Abstract

Accurate stratification of tumors is imperative for adequate cancer management. In addition to staging, morphological subtyping allows stratification of patients into additional prognostic groups. In this study, we used an image-based computational method on pan-cytokeratin immunohistochemical (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 haematoxylin-eosin (H&E) 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.

Abstract

Accurate stratification of tumors is imperative for adequate cancer management. In addition to staging, morphological subtyping allows stratification of patients into additional prognostic groups. In this study, we used an image-based computational method on pan-cytokeratin immunohistochemical (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 haematoxylin-eosin (H&E) 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:31 March 2017
Deposited On:27 Apr 2017 06:40
Last Modified:16 May 2017 01:03
Publisher:American Association for Cancer Research
ISSN:0008-5472
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1158/0008-5472.CAN-16-2363
PubMed ID:28364001

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Embargo till: 2018-03-31