Nectins constitute a family of Ca(2+)-independent immunoglobulin-like adhesion molecules. They are involved in cell proliferation, morphogenesis, growth, development, and immune modulation. Due to their broad involvement in physiological processes, extensive research is being conducted on the expression of individual nectins in a variety of cancers and their potential in diagnosis, prognosis, and treatment. The overexpression of nectin-1 may be a poor prognostic factor in gastrointestinal cancers (intestine and pancreas). Similarly, the overexpression of nectin-2 is a worse prognostic factor (greater tumor advancement and shorter patient survival) in cancers such as gallbladder, esophagus, and breast cancer. Changes in nectin-3 expression also affect the advancement of, e.g., colorectal cancer. Additionally, a significant factor here seems to be the change in the localization of nectin-3 expression within cellular structures. The most extensively studied nectin-4 also shows prognostic potential in many cancers. Most often, its high expression correlates with poor prognosis (e.g., gastric cancer), but it may also be a positive prognostic factor, e.g., in salivary gland cancer. Therapy based on nectin-4 is already known and used in the case of urothelial cancers. The expression of nectin-like protein 5 (necl-5) also shows prognostic and therapeutic potential in pancreatic and lung cancers, as well as in multiple myeloma.

Reliable indicators of cancer advancement have actively been sought recently. The detection of colorectal cancer progression markers is essential in improving diagnostic and therapeutic protocols. The aim of the study was to investigate the profile of E-cadherin expression in colorectal cancer tissue depending on the TNM staging and its correlation with several clinical and histopathological features. The study included 55 colorectal cancer patients admitted to the surgical ward for elective surgery. Tissue samples were obtained from resected specimens. Different distributions of E-cadherin expression within tumors were observed; the highest percentage of positive E-cadherin expression was found in the invasive front and in the tumor center. Additionally, the different cellular distribution of E-cadherin expression was noticed; weak membranous E-cadherin expression was the highest in the invasive front and in the budding sites, but a strong membranous pattern was most frequent in the tumor center. Various distributions of E-cadherin expression depending on cancer progression were also found; E-cadherin expression in node-positive patients was lower in the tumor center and in the tumor invasive front, whereas, in patients with distant metastases, the expression of E-Cadherin was lower in the budding sites. In patients with higher TNM stages, E-cadherin expression was lower within the tumor (in the budding sites, tumor center, and invasive front). In tumors with lymphoid follicles, E-cadherin expression was higher in all localizations within the primary tumor. E-cadherin expression in the tumor center was also lower in tumors with some higher tumor budding parameters (areas of poorly differentiated components and poorly differentiated clusters). E-cadherin expression was found to be lower at the tumor center in younger individuals, at the budding sites in men, and at the surrounding lymph nodes in rectal tumors. Low E-cadherin expression appears to be a reliable indicator of higher cancer staging and progression. When assessing the advancement of cancer, apart from the TNM classification, it is beneficial to also consider the expression of E-cadherin. High tumor budding, the poverty of lymphoid follicles, and low E-cadherin expression analyzed simultaneously may contribute to a reliable assessment of colorectal cancer staging. These three histopathological features complement each other, and their investigation, together with conventional tumor staging and grading, may be very helpful in predicting the prognosis of colorectal cancer patients and qualifying them for the best treatment. The role of E-cadherin in the diagnosis and treatment of colorectal cancer, as a part of a personalized medicine strategy, still requires comprehensive, prospective clinical evaluations to precisely target the optimal therapies for the right patients at the right time.

Background: Remodeling of epithelial junctional architecture contributes to colorectal cancer (CRC) progression; however, the spatial organization linking tight-junction components to early dissemination remains incompletely characterized. Claudin-2 (CLDN-2) is frequently upregulated in CRC, yet whether it is associated with compartment-specific epithelial remodeling has not been systematically examined. Methods: In a retrospective single-center cohort of 54 surgically resected CRCs, we integrated clinicopathological variables, quantitative tumor budding counts, compartment-specific membranous E-cadherin expression, lymphovascular invasion, lymphoid follicles, and immune-cell densities. Analyses focused on spatial structural relationships within the tumor. Results: Higher CLDN-2 expression was enriched among node-positive tumors and advanced TNM stages. CLDN-2–higher tumors exhibited increased tumor budding and spatially selective adhesion remodeling, characterized by reduced membranous E–cadherin at the invasive front and budding sites, with more preserved membranous epithelial organization within metastatic lymph-node deposits. Descriptive co-occurrence and correlation analyses demonstrated concordant spatial relationships among CLDN-2 expression, tumor budding, nodal involvement, lymphovascular invasion, and compartment-specific E-cadherin patterns. In contrast, immune-related parameters showed weaker differentiation across CLDN-2 strata. Conclusions: CLDN-2 expression is associated with spatial epithelial remodeling in colorectal cancer, characterized by compartment-specific adhesion changes and increased microinvasive activity. The findings support a model in which CLDN-2 expression aligns with an invasion-associated epithelial configuration linked to tumor budding and nodal dissemination. These observations warrant validation in independent cohorts with outcome data.