Refined prognostic evaluation in colon carcinoma using immunohistochemical galectin fingerprinting

Abstract

BACKGROUND Knowledge of the expression of the galectins in human colon carcinomas is mainly restricted to galectin‐3 and, to a lesser extent, galectin‐1. The current study analyzed the prognostic values contributed by galectin‐1, galectin‐3, galectin‐4, and galectin‐8 in cases of colon carcinoma. METHODS The authors selected 55 colon carcinomas (including 10 Dukes A, 16 Dukes B, 15 Dukes C, and 14 metastatic tumors that the authors labeled “Stage D”). The immunohistochemical levels of expression of the four galectins were determined quantitatively by means of computer‐assisted microscopy. RESULTS The data from the current study indicate that the four galectins under study are associated with significant and separate prognostic values that depend on the Dukes stage of the colon tumor. In particular, the authors observed a significant prognostic value associated with galectins‐1, ‐3, and ‐4 in Dukes A and B colon tumors. In addition, significant prognostic value also was associated with galectin‐8 in Dukes C and D colon tumors. The prognostic values associated with the levels of expression of galectin‐1 and galectin‐4 in Dukes A and B tumors appear to be independent of the Dukes stage. The same feature was observed when galectin‐4 and galectin‐8 were analyzed in the complete series. CONCLUSIONS The data from the current study strongly suggest that galectins‐1, ‐3, and ‐4 may be involved in the early stages of human colon carcinoma development and that galectin‐8 is involved in the later stages. Cancer 2003;97:1849–58. © 2003 American Cancer Society. DOI 10.1002/cncr.11268

C4.4A as a candidate marker in the diagnosis of colorectal cancer

“…Importantly, C4.4A expression was also largely absent in inflamed colonic mucosa and liver. C4.4A expression was compared with the expression of EpCAM, galectin-3 and CO-029, which have been described as reliable markers in colorectal cancer (Sela et al, 1989;Armstrong and Eck, 2003;Nagy et al, 2003). With respect to sensitivity, EpCAM (liver metastases, only) and CO-029 were superior to C4.4A.…”

“…However, C4.4A expression was also seen in 40% of chronic pancreatitis tissue (Table 2A). To validate the reliability of C4.4A as a tumour marker, particularly for colorectal cancer, expression of C4.4A was compared with galectin-3, EpCAM and CO-029 expression, that all three have been described to be upregulated in colorectal cancer (Sela et al, 1989;Armstrong and Eck, 2003;Nagy et al, 2003). In primary colorectal cancer, the sensitivity for C4.4A was 0.85 (95% CI: 0.73 -0.84) and the specificity 1.00 (95% CI: 0.94 -1.00).…”

Surface profiles of live colorectal cancer cells and tumor infiltrating lymphocytes from surgical samples correspond to prognostic categories

“…An absence of TIL may enable metastatic invasion, as CRC cells transition to a more invasive, metastatic mesenchymal phenotype (Gout and Huot, 2008). We detected evidence of epithelial to mesenchymal transitioning indicated by the replacement of the epithelial adhesion marker, CD49d (Stallmach et al, 1992), with the endothelial adhesion and migration antigens, CD24, CA19-9 and Galectin-4 (Yamada et al, 1995;Nagy et al, 2003;Sagiv et al, 2006) on CRC cells in the systemic relapse group.…”

Nuclear galectin-3 expression is an independent predictive factor of recurrence for adenocarcinoma and squamous cell carcinoma of the lung

“…18 The specificity of the galectin-3 antibody was checked by immunoblotting and ELISA assays with controls to exclude any crossreactivity to other galectins (especially galectin-1, which is abundant in human lungs), as previously detailed. [18][19][20]33 An internal positive control consisted in the expression of galectin-3 (also labeled Mac-2) by alveolar macrophages. The negative control sections were immunostained under the same conditions, but with the omission of the primary antibody.…”

“…15,16 Galectins are involved in cell growth, apoptosis and cell migration features. [17][18][19][20] Of these 14 galectins, galectin-3, a chimera-type galectin, is of special interest since its structure harbors a sugar-combining site, a collagensensitive stalk and a short N-terminated section, acting as a target for phosphorylation. 21 What is particularly intriguing about this sole chimera-type galectin is its presence in nuclear, cytoplasmic and extracellular sites, 22 its ability to interact with a variety of carbohydrate and protein ligands and to form pentamers with unique crosslinking abilities, 23 its strong antiapoptotic activity coupled with the nuclear export of the phosphorylated form (for example in chemotherapeutic treatment), 24 and its effect on promoter activity of cyclin D1, 25 which is a prognostic marker in the adenocarcinoma subgroup of lung carcinomas.…”