Published online Sep 28, 2018. doi: 10.3748/wjg.v24.i36.4164
Peer-review started: July 16, 2018
First decision: July 24, 2018
Revised: August 15, 2018
Accepted: August 24, 2018
Article in press: August 24, 2018
Published online: September 28, 2018
In Poland, colorectal carcinoma (CRC) is the second most common cancer in men and woman, with the third leading causes of cancer deaths in Greater Poland Region. Altered mucin expression is correlated with the prognosis of this cancer. In vivo as well as in vitro studies on the expression of mucins may have also therapeutic implications.
The role of mucin expression at various stages of the colon carcinogenesis is incomplete. The prognostic role of mucins in the mucinous subtypes of CRC is poorly known. Research into the role of mucins in pathogenesis and CRC clinical studies (especially in mucinous subtypes) are also current topics from a methodological point of view. The lack of standardized methods of quantitative evaluation of mucins expression (especially at tissue level) and/or frequent lack of control groups, are a great difficulty in comparative analysis.
Current research determines tissue expression (mRNA, protein) of membrane-bound mucin [mucin 1 (MUC1)] and secretory mucin [mucin 2 (MUC2)] in healthy and colorectal cancer tissue samples and evaluates the relationship between tissue expression of both mucins and selected clinicopathological data of the patients with CRC.
The research on tissue expression of two types of mucins (MUC1 and MUC2) in cancerous and normal colorectal tissue samples was performed using real-time quantitative polymerase chain reaction (RT-qPCR) to evaluate expression of transcripts, immunohistochemistry (IHC) for demonstrating apomucins localization, and the morphometric analysis of intensity of IHC reaction using modern HSV filter software.
Significantly higher expression of the MUC1 mRNA in the CRC, while MUC2 transcript expression was comparable with the control colorectal samples. Using immunohistochemistry, we observed lower MUC2 protein as compared to control tissue. MUC2 protein expression correlated negatively with cellular proliferation (Ki-67 antigen expression) and expression of mutated form of p53. In neoplastic tissue of CRC it was observed also higher MUC1/MUC2 ratio as compared with healthy colorectal tissue. Higher expression of MUC2 was a feature of mucinous CRC subtypes, and characterized higher histological stage of tumors. Future study is required to explain molecular mechanisms of CRC carcinogenesis including mucins and TP53 pathway.
Our study confirmed that the colorectal carcinogenesis is closely related to overexpression of MUC1 and the decline in MUC2 expression. The use of increasingly repetitive and reliable method for the quantitative evaluation of mucins expression may prove useful to evaluate different patterns of IHC reaction (membranous, cytoplasmic, etc.) and can be useful in various subtype of colorectal cancer, as our research shows (mucinous vs nonmucinous CRC). Both the microscopic demonstration of evident MUC1 expression, especially in healthy colorectal tissue (control), and morphometric quantitative evaluation (Filter HSV program) of membranous (MUC1) and secreted (MUC2) expression is the novelty of the present work. The quantitative method used in the current study, can be used for further comparative research and to evaluate tissue expression of other types of mucins in CRC. The use of quantitative methods in immunocytochemistry can improve the detection of tissue markers in CRC and assess their true value in daily medical practice.
This study proposed, that the examination of the tissue expression of MUC1 and MUC2 (mRNA, protein), should use modern methods of quantitative assessment of transcripts (e.g. RT-qPCR), and more reliable morphometric methods (e.g. HSV filter software). Only these methods could improve the diagnostic/prognostic usefulness of mucins as tissue biomarkers in CRC patients. A better explanation of molecular mechanisms in the colorectal carcinogenesis with mucin involvement requires further testing, also on an in vitro model. These results could be the basis for further studies to understand the carcinogenesis of colorectal cancer.