Changes in Galectin-7 and Cytokeratin-19 Expression during the Progression of Malignancy in Thyroid Tumors: Diagnostic and Biological Implications

Abstract

Galectin-7 is associated with p53-dependent onset of apoptosis and proliferation control/differentiation in keratinocyte development. It is also upregulated in chemically induced rat mammary carcinogenesis. Because the levels of expression of galectin-7 have never been investigated in thyroid tumors (in contrast to those of galectin-1 and -3 associated with malignancy), we initiated analysis of the expression of galectin-7 in benign and malignant thyroid lesions together with that of cytokeratin-19 (CK19), a marker already demonstrated to be useful in diagnosing this kind of lesion. The immunohistochemical expression levels were quantitatively determined by means of computerassisted microscopy on a series of 84 thyroid lesions including 10 multinodular goiters, 32 adenomas, and 42 carcinomas. Our data clearly indicate a marked down-regulation of galectin-7 expression in a large proportion of adenomas (including the normomacrofollicular, microfollicular, and trabecular variants) if compared with carcinomas. In accordance with results of previous studies, a marked up-regulation of CK19 expression was observed in the thyroid carcinomas, and this contrasted in particular with the low CK19 expression observed in the microfollicular adenomas. Of importance for diagnostic implications, the combination of these two markers enabled our series of microfollicular adenomas (characterized by low galectin-7 and CK19 expression) to be efficiently distinguished from the encapsulated follicular variant of papillary thyroid carcinomas (high galectin-7 and CK19 expression).

Galectin-7 in Lymphoma: Elevated Expression in Human Lymphoid Malignancies and Decreased Lymphoma Dissemination by Antisense Strategies in Experimental Model

“…Galectin-7 is expressed in human malignant thyroid tumors and type IV hypopharyngeal squamous cell carcinoma (13,25). We have also shown that galectin-7 is expressed in murine aggressive lymphoma cells but not in normal lymphocytes (14).…”

“…At first glance, because galectin-7 functions as a regulator of differentiation and apoptosis in several cell types (16,(28)(29)(30), one would expect that galectin-7 should favor the elimination of tumor cells during cancer progression. However, in addition to aggressive lymphoma cells, high levels of galectin-7 expression have been reported in chemically induced rat mammary tumors (12), in human malignant thyroid tissues (13), and in type IV hypopharyngeal squamous cell carcinoma (25). This apparent discrepancy can be explained by the fact that, depending on the cell types, galectin-7 could be preferentially found in the cytoplasm, in the nucleus, or in the extracellular space, thereby having distinct functions according to its cellular localization (29).…”

“…Lu et al (12) have first reported that galectin-7 was overexpressed in rat mammary carcinomas induced by 7,12-dimethylbenz(a)anthraacene. Rorive et al (13) have subsequently observed that galectin-7 expression was markedly down-regulated in benign thyroid tumors compared with malignant ones. Using an approach based on genomic analysis of an aggressive lymphoma variant and its nonaggressive parental cells, we found that the most prominent change among the genes tested was the strong up-regulation of galectin-7 (14).…”

Overexpression of Galectin-7, A Myoepithelial Cell Marker, Enhances Spontaneous Metastasis of Breast Cancer Cells

“…They reported that galectin-7 expression was restricted to mammary carcinomas and was not detected in any other normal tissues examined in the adult rat, providing the first indication that galectin-7 could be associated with tumor progression. Rorive et al 11 later observed that galectin-7 expression was markedly higher in different forms of papillary carcinomas than in benign thyroid tumors. Recent work in lymphoma further supported the idea that galectin-7 may promote tumorigenesis.…”

Roles of Galectin-7 in Cancer

“…Immuno-histochemical studies revealed higher percentage of galectin-7 positive cells as well as its elevated expression in carcinomas in comparison to adenomas (Rorive et al, 2002;Than et al, 2008). In contrast, immuno-histochemical study showed no significant difference in galectin-7 expression between benign and malignant forms of thyroid cancer (Than et al, 2008).…”