Tumor volume of colon carcinoma is related to the invasive pattern but not to the expression of cell adhesion proteins

Abstract

Tumor volume increases during growth and due to tumor progression various mutations appear that may cause phenotypic changes. The invasive pattern may thus be affected resulting in a more disorganized growth. This phenomenon might be due to mutations in the genome of the adhesion proteins, which are responsible for the structural integrity of epithelial tissue. Tumor volume was assessed in whole mount sections of 33 colon carcinomas using Cavalieri's principle. Images from the entire invasive border were captured and used for calculating the irregularity of the border (Complexity Index). The expression of the adhesion proteins E‐cadherin, β‐catenin, Claudin 2 and Occludin was assessed after immunohistochemical staining of two randomly selected areas of the invasive front of the tumor. Statistical significance for differences in volume was obtained for tumor Complexity Index, tumor stage (pT) and lymph node status (pN). Expression of adhesion proteins was significantly perturbed in the tumors compared with normal mucosa but only infrequently correlated to tumor differentiation or invasive pattern. The results show that when tumor volume increases the invasive pattern becomes more irregular which is compatible with tumor progression. A direct contribution of adhesion protein derangement to this process appears to be insignificant.

Down-regulation of μ-protocadherin expression is a common event in colorectal carcinogenesis

“…In fact, a number of observations have described a decrease of E-cadherin expression in such neoplastic conditions [2,27,28], whereas other studies failed to demonstrate this finding [29,30,31]. In our study, only 4 tumors showed absence or marked reduction of E-cadherin expression in complete accordance with a recent article that observed this pattern in only 4 of 33 CRCs examined [32]. It is worth underlining that loss of E-cadherin expression was exclusively detected in the μ-protocadherin-positive set of CRCs and, therefore, it did not interfere with subcellular localization of β-catenin, which always exhibited a membranous staining in such samples.…”

Characterization of Clinical and Molecular Features Related to the Downregulated Expression of μ-Protocadherin in Colorectal Cancer

“…These findings confirmed the data that have been previously published by our and other research groups, indicating a controversial role of E-cadherin in CRC [4,[18][19][20] The expression changes detected for some of the other cadherin superfamily members, exhibiting a down-regulated (PCDH24) or upregulated (CDH3) expression in the tumor progression process from normal colorectal mucosa to colorectal adenoma and carcinoma, have been already observed by other authors [21,22], demonstrating the reliability of our bioinformatic analysis conditions. Based on previous reports evidencing that the lack of expression of cadherin genes is rarely due to gene mutations [23] and it is more frequently the consequence of epigenetic changes [24,25] we perfomed a methylation analysis of μ-protocadherin promoter region in colorectal adenomas/carcinomas and CRC cell lines.…”

Effects of supplemental calcium and vitamin D on tight‐junction proteins and mucin‐12 expression in the normal rectal mucosa of colorectal adenoma patients

“…OCLD seals TJs and is involved in paracellular permeability . OCLD has also been implicated in nonbarrier roles, such as cell proliferation regulation, and was found to be less highly expressed in colorectal tumors than in the normal colon mucosa . The mucus layer of the colon consists of high molecular weight glycoproteins called mucins, which are synthesized mostly by goblet cells in the colon epithelium .…”

“…roles, such as cell proliferation regulation, 9 and was found to be less highly expressed in colorectal tumors than in the normal colon mucosa. [10][11][12] The mucus layer of the colon consists of high molecular weight glycoproteins called mucins, which are synthesized mostly by goblet cells in the colon epithelium. 13 One type of mucin, transmembrane mucins, is also expressed by colonocytes, 14 and, in addition to providing a physical barrier and the first layer of defense against invasive pathogens, may activate signal transduction pathways that regulate inflammation, cell differentiation, and apoptosis.…”