High level of galectin-1 expression is a negative prognostic predictor of recurrence in laryngeal squamous cell carcinomas

Abstract

Monitoring of gene-expression profiles is assumed to refine tumor characterization of laryngeal squamous cell carcinomas (LSCCs) with a therapeutic perspective. This is especially expected for adhesion/growth-regulatory effectors such as galectins, a class of endogenous lectins. Using computer-assisted microscopy, we investigated the prognostic value contributed by the quantitative determination of the immunohistochemical levels of expression of galectin-1,-3 and-7 in a series of 62 LSCCs including 42 low-and 20 highstage LSCCs. As galectin-1 may have a key role leading to a tumor escape from immune surveillance, we also investigated whether or not the level of galectin-1 expression correlated with lymphocyte infiltration in LSCCs. The immunohistochemical determination of expression of galectin-1 is of prognostic value in human squamous laryngeal cancers. LSCCs that display high levels of galectin-1 have worse prognoses than laryngeal cancers with low levels of galectin-1 expression. Elevation of galectin-1 levels in laryngeal cancers can contribute to the process of tumor immune escape by killing the activated T-cells and other protumoral activities such as promoting motility or activity of oncogenic H-Ras proteins. The quantitative determination of galectin-1 in LSCCs is an independent prognostic marker when opposed to TNM staging. It has the potential to identify patients unlikely to benefit from T-cell-mediated immunotherapy, although the definitive effector function from its pro-and antitumoral activity profile has not been delineated.

Helicase-like transcription factor exhibits increased expression and altered intracellular distribution during tumor progression in hypopharyngeal and laryngeal squamous cell carcinomas

“…This point relates directly to the fact that cancers of the upper aerodigestive tract are heterogeneous in their neoplastic processes, each of which requires its own unique set of epidemiologic, anatomic, pathologic, and therapeutic considerations. Laryngeal and hypopharyngeal CAs present several significant clinical and biological differences which could be considered to partly explain the observed divergence in HLTF expression: (1) most hypopharyngeal CA patients (70-80% of cases) presented advanced stages (III and IV) at the time of diagnosis, whereas laryngeal CA patients were most frequently diagnosed at early stages (70-90% of cases presented stages I and II) [25]; (2) at a similar stage, hypopharyngeal CAs were associated with worse prognosis than laryngeal CAs, [25]; (3) well-differentiated CAs were common in larynx, whereas poorly differentiated tumors were more frequently located in hypopharynx [26], (4) in laryngeal CAs, there was a significant relationship between the presence of intratumoral lymphatics and nodal metastases which was not the case for hypopharyngeal CAs [27]; (5) the relationship of galectin-7 (an endogenous lectin with a wide range of extra-and intra-cellular functions mediated by protein-carbohydrate and protein-protein interactions) expression to aggressiveness appeared to depend on the location in the upper aerodigestive tracts: in hypopharyngeal CAs, galectin-7 overexpression was associated with worse prognosis, while this was not observed in laryngeal CAs [28,29]. Previous studies described HLTF promoter hypermethylation in a significant number of cases of colorectal and gastric carcinomas, whereas only one case of esophageal carcinoma presented this silencing [4][5][6][7][8][9][10][11][12][13].…”

Mechanism of tumor cell-induced T-cell apoptosis mediated by galectin-1

“…In tumors, Gal-1 is produced by tumor cells and/or tumorassociated stroma cells [4,[39][40][41] and cell-free ECM absorbs locally secreted Gal-1 as well [36]. Moreover, it has been previously shown that tumor-associated blood vessel endothelium (TABVE) expresses high levels of Gal-1 in contrast to healthy endothelial cells [42,43].…”

Increased expression and altered intracellular distribution of adhesion/growth‐regulatory lectins galectins‐1 and ‐7 during tumour progression in hypopharyngeal and laryngeal squamous cell carcinomas

“…These data suggest that the immunohistochemical determination of galectin‐7 expression in the case of high‐risk hypopharyngeal cancers is a meaningful tool to identify patients who might benefit from aggressive postsurgical adjuvant therapy 24 . Moreover, the level of expression of galectin‐1 contributes to the prognosis of the recurrence of laryngeal tumours and, to a lesser extent, of pharyngeal tumours after surgery, and to patients’ survival prospects 24,25 . Elevation of galectin‐1 levels in LSCCs could contribute to the process of tumour development by killing activated T cells and by promoting motility or activity of oncogenic H‐Ras proteins 25 .…”

“…Our previous report concerning stage IV hypopharyngeal squamous cell carcinoma (HSCC) was the first to demonstrate that high levels of galectin‐7 expression could be associated with rapid recurrence rates and a dismal prognosis, features weakly observed with galectin‐1 24 . We have also previously investigated the prognostic value of these same galectins in a series of laryngeal squamous cell carcinomas (LSCCs) and shown that high levels of galectin‐1 expression are associated with a poor relapse‐free and overall survival rate 25 . In the present study we have used quantitative immunohistochemistry in a series of 78 cases of stage IV HSCC and 56 cases of LSCC (stages I, II and IV) in comparison with normal controls and dysplastic tissues from peritumoral regions to address the following questions: do the levels of expression of galectins‐1 and ‐7 change with the course of the disease?…”