From Dukes-MAC Staging System to Molecular Classification: Evolving Concepts in Colorectal Cancer

Abstract

This historical review aimed to summarize the main changes that colorectal carcinoma (CRC) staging systems suffered over time, starting from the creation of the classical Duke’s classification, modified Astler–Coller staging, internationally used TNM (T—primary tumor, N—regional lymph nodes’ status, M—distant metastases) staging system, and ending with molecular classifications and epithelial–mesenchymal transition (EMT) concept. Besides currently used staging parameters, this paper briefly presents the author’s contribution in creating an immunohistochemical (IHC)-based molecular classification of CRC. It refers to the identification of three molecular groups of CRCs (epithelial, mesenchymal and hybrid) based on the IHC markers E-cadherin, β-catenin, maspin, and vimentin. Maspin is a novel IHC antibody helpful for tumor budding assessment, which role depends on its subcellular localization (cytoplasm vs. nuclei). The long road of updating the staging criteria for CRC has not come to an end. The newest prognostic biomarkers, aimed to be included in the molecular classifications, exert predictive roles, and become more and more important for targeted therapy decisions.

Molecular subtyping in colorectal cancer: A bridge to personalized therapy (Review)

“…For example, based on the CCS typing of CRC, five markers (CDX2, FRMD6, HTR2B, ZEB1 and KER) were selected from a total of 146 characteristic genes in the CCS classifier, and were subjected to IHC staining and further classified in combination with MSI status (158). The accuracy of molecular diagnostic tests largely depends on the quality of paraffin-embedded tissues and the identification of tumor-rich regions, which pose an additional task for pathologists (159,160).…”

“…A comprehensive analysis of muscle-infiltrating bladder cancer showed that multi-omics classification was more effective than mRNA-based clustering analysis for guiding clinical decision-making (157,168). Banias et al (159) described three molecular subtypes of CRC (epithelial, mesenchymal and mixed) based on the IHC markers E-cadherin, β-catenin, maspin and vimentin. A novel relationship between intracellular maspin expression and MSI, tumor budding and prognosis has far-reaching clinical significance.…”

Serum Selenium Concentration as a Potential Diagnostic Marker for Early-Stage Colorectal Cancer: A Comparative Study

“…The clinical advancement of CRC was based on the Dukes’ classification as modified by Astler and Coller [ 25 ]. The number of samples corresponding to stage I – T1N0M0 (group A according to Dukes’ original classification and as modified by Astler and Coller) was 21 samples; for stage I – T2N0M0 (group A according to Dukes’ original classification and as modified by Astler and Coller), 19 samples; for stage IIA – T3N0M0 (group B according to Dukes’ original classification and B2 in the classification as modified by Astler and Coller), 7 samples; for stage IIB – T4aN0M0 (group B according to Dukes’ original classification and B2 in the classification as modified by Astler and Coller), 5 samples; for stage IIC – 4N0M0 (group B according to Dukes’ original classification and B3A in the classification as modified by Astler and Coller), 4 samples.…”

Use of Oleuropein and Hydroxytyrosol for Cancer Prevention and Treatment: Considerations about How Bioavailability and Metabolism Impact Their Adoption in Clinical Routine

“…It is characterized by high rates of acquired multidrug resistance, leading to chemotherapy failure, relapse, and development of lethal disease [ 186 , 187 ]. The classical Dukes’ classification distinguishes between “type A” and “type B” tumors, according to the absence or presence of tumor infiltration in extra-rectal tissues, respectively, and designates as “type C” those tumors with regional lymph node metastasis, and as “type C1” and “type C2” those malignancies exhibiting involvement of more distant lymph nodes [ 188 ].…”