Markers of Epithelial–Mesenchymal Transition and Mucinous Histology Are Significant Predictors of Disease Severity and Tumor Characteristics in Early-Onset Colorectal Cancer

Author:

Djikic Rom Aleksandra1ORCID,Dragicevic Sandra2ORCID,Jankovic Radmila3ORCID,Radojevic Skodric Sanja3,Sabljak Predrag45,Markovic Velimir45,Stojkovic Jovana Rosic4ORCID,Barisic Goran45,Nikolic Aleksandra2ORCID

Affiliation:

1. Department of Pathology, Pathohistology and Medical Cytology, University Clinical Center of Serbia, Pasterova 2, 11000 Belgrade, Serbia

2. Gene Regulation in Cancer Group, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11000 Belgrade, Serbia

3. Institute of Pathology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia

4. Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia

5. Clinic for Digestive Surgery—First Surgical Clinic, University Clinical Center of Serbia, 11000 Belgrade, Serbia

Abstract

Approximately 20% of patients with colorectal cancer (CRC) are diagnosed with a mucinous subtype of this tumor, have a worse prognosis, and often show resistance to available therapies. Molecules from the mucin family are involved in the regulation of epithelial–mesenchymal transition (EMT), which significantly determines the cancer aggressiveness. This study aimed to examine the diagnostic and prognostic significance of mucinous histology and EMT markers in patients with early-onset CRC and their association with disease severity and tumor characteristics. This study included tumor tissue samples from 106 patients diagnosed with CRC before the age of 45, 53 with mucinous and 53 with non-mucinous tumors. The EMT status was determined by immunohistochemical analysis of E-cadherin and Vimentin in tissue sections. Mucinous tumors had significantly higher Mucin-1 (p < 0.001) and cytoplasmic E-cadherin (p = 0.043) scores; they were significantly less differentiated (p = 0.007), more advanced (p = 0.027), and predominately affected right the colon (p = 0.039) compared to non-mucinous tumors. Epithelial tumors were significantly better differentiated (p = 0.034) and with less prominent tumor budding (p < 0.001) than mesenchymal tumors. Mucin-1 and Vimentin were independent predictors of tumor differentiation (p = 0.006) and budding (p = 0.001), respectively. Mucinous histology and EMT markers are significant predictors of disease severity and tumor characteristics in early-onset colorectal cancer.

Funder

Serbian Academy of Sciences and Arts

Ministry of Education, Science and Technological Development of the Republic of Serbia

Publisher

MDPI AG

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