Are Stem Cell Marker Expression and Cd133 Analysis Relevant to Differentiate Colorectal Cancer?

Abstract

Background: CD133 and AXL have been described as cancer stem cell markers, and c-MYC as a key regulatory cellular mechanism in colorectal cancer (CRC). Aim: Evaluate the prognostic role of the biomarkers CD133, AXL and c-MYC and their association with clinicopathologic characteristics in colorectal adenocarcinomas and adenomas. Methods: A total of 156 patients with UICC stage I-IV adenocarcinomas (n=122) and adenomas (n=34) were analyzed. Tissue microarrays (TMA) from primary tumors and polyps for CD133, c-MYC and AXL expression were performed and analyzed for their significance with clinicopathologic characteristics. Results: Poorly differentiated adenocarcinomas and disease progression were independent risk factors for poor overall survival. The median overall survival time was 30 months. Positive CD133 expression (35.9% of all cases), particularly of right-sided CRCs (44.8% of the CD133+ cases), was negatively correlated with death in the univariate analysis, which did not reach significance in the multivariate analysis. c-MYC (15.4% of all cases) was predominantly expressed in advanced-stage patients with distant (non-pulmonary/non-hepatic) metastasis. AXL expression was found only occasionally, and predominantly dominated in adenomas, with less penetrance in high-grade dysplasia. Conclusions: CD133 expression was not associated with inferior overall survival in CRC. While AXL showed inconclusive results, c-MYC expression in primary CRCs was associated with distant metastasis.

Stemness, Inflammation and Epithelial–Mesenchymal Transition in Colorectal Carcinoma: The Intricate Network

“…First, immunohistochemistry is influenced by technological variations regarding: (1) fixation (none versus formalin, pH, time of fixation and cold ischemia); (2) features of the primary antibody (clonality (monoclonal versus polyclonal), clone, concentration, incubation temperature and time); (3) mode (heat-induced versus enzymatic versus none) and features (pH, microwave, temperature, timing) of antigen retrieval; (4) choice of visualisation system; (5) scoring, among others. An indirect hint of technological reasons in the given case is the high proportion of CD133-positive cases observed by immunohistochemistry: 35.9% of all studied cancers and even 44.8% of right-sided carcinomas, as reported by Czeczko et al 2021 [ 30 ]. Further, the inherent complexity of tumour tissues can provide the background for redundant regulatory links.…”

“…correlation between CD133 expression and death rate, confirmed by univariate analysis. Although the correlation did not reach significance in the multivariate analysis, the trend was opposite to the expected association between stemness and worse prognosis [ 30 ]. In addition, Ilie et al concluded that CD133 alone cannot be used to show CSCs.…”

“…In experimental models of CRC, CD133 + CD44 + cells are able to initiate tumours in nude mice [ 29 ]. However, some immunohistochemical studies strongly contradict the value of CD133 as a stem cell marker [ 30 , 31 ]. Thus, Czeczko et al recently reported on a negative ( sic !)…”

Carnoy’s Solution Increases Lymph Nodes Count in Colon Cancer Specimens When Compared to Formalin Fixation: A Randomized Trial

“…Colorectal cancer is one of the most diagnosed cancers worldwide 2 . Surgical resection is the main therapeutic option, and the analysis of at least 12 lymph nodes (LNs) is required to determine staging and prognosis 1 , 3 , 13 . The detection of LN in colorectal specimens is laborious and time-consuming.…”

Which Lesions Are at Higher Risk of Developing Colorectal Carcinomas: Superficially Elevated Serrated Lesions or Depressed Lesions?

“…In recent years, serrated lesions have come to be considered as one of the important pathways of colorectal carcinogenesis and may represent, according to several authors, from 6.0 to 30% of all colorectal carcinomas; however, the percentage of each pathway in this carcinogenesis is not yet known for certain 2 , 12 , 25 . However, they have the potential, yet to be defined, to evolve into invasive cancer, with a molecular profile different from each other and from carcinomas in conventional adenomas 2 , 6 , 7 , 25 , 31 , 32 . A high risk of cancer in sessile serrated adenomas is reported in patients with serrated polyposis syndrome 13 and in the elderly with sessile or protruding components associated with it 18 , 21 .…”