Expression Profiling as Biomarkers in Colorectal Serrated Carcinoma

  • Mari Carmen Turpín Sevilla
  • José García Solano
  • Claudio Navarre
  • Miguel Pérez-Guillermo García
  • Ana Conesa
  • Pablo Conesa Zamora
Reference work entry
Part of the Biomarkers in Disease: Methods, Discoveries and Applications book series

Abstract

Serrated adenocarcinoma (SC) is a recently recognized colorectal cancer (CRC) subtype, accounting for 7.2–9.2 % of CRC. SC has a worse prognosis than conventional carcinoma (CC) probably due to specific features at the invasive front including high-grade tumor budding and cytoplasmic pseudofragments, infiltrating growth pattern, and a weak peritumoral lymphocyte response. SCs also have a different profile of mutations in KRAS or BRAF oncogenes, expression of DNA repair proteins, and MSI status. Histological and immunohistochemical protein expression criteria have been proposed for SC diagnosis. Molecular profile studies have revealed that in agreement with previous observations, SCs have several cellular functions differentially regulated, such as hypoxia-, cytoskeleton-, vesicle transport-, and apoptosis-related pathways, among others. Expressions of several genes that participate in these pathways, like ephrin receptor B2, hippocalcin, and fascin1, have been proposed as biomarkers for differential SC diagnosis. miRNA expression and methylome signatures seem to corroborate these functions. All these findings suggest that the correct SC diagnosis may have important clinical implications and that the identified pathways and molecular targets could be exploited in the interest of SC specific patient follow-up and treatment.

Keywords

Molecular profiling Colorectal cancer Serrated carcinoma Conventional carcinoma Microsatellite instability CpG island methylation phenotype 

List of Abbreviations and Genes

Abbreviations

CC

Conventional Carcinoma

CIMP

CpG island Methylation Phenotype

CRC

Colorectal Carcinoma

CyPs

Cytoplasmic Pseudofragments

EMT

Epithelial-Mesenchymal Transition

HH

Hedgehog Signaling Pathway

IHC

Immunohistochemistry

LOH

Loss of Heterozygosity

miRNA

MicroRNA

MSI

Microsatellite Instability

MSI-H

High Microsatellite Instability

MSI-L

Low Microsatellite Instability

PLI

Peritumoral Lymphocytic Infiltrate

SA

Serrated Adenoma

SC

Serrated Carcinoma

SSA

Sessile Serrated Adenoma

TB

Tumor Budding

TGP

Tumor Growth Pattern

TILs

Tumor Infiltrating Lymphocytes

Genes

APC

Adenomatous Polyposis Coli

EGFR

Epidermal Growth Factor Receptor

EPHB2

Ephrin Receptor B2

FSCN1

Fascin 1

HIF-1α

Hypoxia-Inducible Factor 1 α

HPCA

Hippocalcin

MGMT

O-6-Methylguanine-DNA Methyltransferase

MLH1

DNA Mismatch Repair Protein Mlh1

MSH2 and MSH6

DNA Mismatch Repair Protein MSH2 and MSH6

NAIP

Neuronal Apoptosis Inhibitory Protein

PTCH1

Patched

SMO

Smoothened

VEGF

Vascular Endothelial Growth Factor

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Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Mari Carmen Turpín Sevilla
    • 1
    • 2
  • José García Solano
    • 3
    • 4
  • Claudio Navarre
    • 5
  • Miguel Pérez-Guillermo García
    • 3
  • Ana Conesa
    • 5
  • Pablo Conesa Zamora
    • 3
    • 4
  1. 1.Department of Pathology(HGUSL)CartagenaSpain
  2. 2.University Francisco of VitoriaMadridSpain
  3. 3.Department of PathologyHospital General Universitario Santa Lucia (HGUSL)CartagenaSpain
  4. 4.Facultad de Ciencias de la SaludCatholic University of Murcia (UCAM)MurciaSpain
  5. 5.Genomics of Gene Expression LaboratoryCentro de Investigación Príncipe Felipe (CIPF)ValenciaSpain

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