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Expression Profiling as Biomarkers in Colorectal Serrated Carcinoma

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Biomarkers in Cancer

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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.

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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

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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    Authors and Affiliations

    1. Department of Pathology (HGUSL) Cartagena, Spain; , University Francisco of Vitoria, Mezquita SN, 30202, Madrid, Spain

      Mari Carmen Turpín Sevilla

    2. Department of Pathology, Hospital General Universitario Santa Lucia (HGUSL), Mezquita SN, 30202, Cartagena, Spain

      José García Solano, Miguel Pérez-Guillermo García & Pablo Conesa Zamora

    3. Facultad de Ciencias de la Salud, Catholic University of Murcia (UCAM), Murcia, Spain

      José García Solano & Pablo Conesa Zamora

    4. Genomics of Gene Expression Laboratory, Centro de Investigación Príncipe Felipe (CIPF), Eduardo Primo Yúfera 3, Valencia, 46012, Spain

      Claudio Navarre & Ana Conesa

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    1. Mari Carmen Turpín Sevilla
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    2. José García Solano
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    3. Claudio Navarre
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    4. Miguel Pérez-Guillermo García
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    5. Ana Conesa
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    6. Pablo Conesa Zamora
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    Correspondence to Pablo Conesa Zamora .

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    Editors and Affiliations

    1. Department of Nutrition and Dietetics Division of Diabetes & Nutritional Sciences, Faculty of Life Sciences & Medicine King’s College London, London, United Kingdom

      Victor R. Preedy

    2. Department of Biomedical Sciences Faculty of Science and Technology, University of Westminster, London, United Kingdom

      Vinood B. Patel

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    Sevilla, M.C.T., Solano, J.G., Navarre, C., García, M.PG., Conesa, A., Zamora, P.C. (2014). Expression Profiling as Biomarkers in Colorectal Serrated Carcinoma. In: Preedy, V., Patel, V. (eds) Biomarkers in Cancer. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7744-6_4-1

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    • DOI: https://doi.org/10.1007/978-94-007-7744-6_4-1

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