The helicase-like transcription factor (HLTF) belongs to the SWI/SNF family of chromatin-remodeling factors. Several SWI/SNF genes are disrupted in cancer, suggesting their possible role as tumor suppressors. Similarly, the HLTF gene was found to be inactivated by hypermethylation in a significant number of colon, gastric and uterine tumors, indicating that HLTF silencing may confer a growth advantage and that HLTF could be considered as a tumor suppressor gene. However, 20-fold HLTF overexpression was detected in various transformed cell lines, suggesting that HLTF could be associated with neoplastic transformation and act more like an oncogene. Moreover, HLTF activation was recently linked to the initial steps of carcinogenesis in an experimental model of estrogen-induced kidney tumors. Those apparently contradictory observations suggest that HLTF might play various roles in cancer. In this review, we will try to reconcile all these data in order to specify the role of HLTF in cancer progression.

Our data reveal an association between level of presence of galectin-3 and neoplastic progression of HSCCs and LSCCs.

Our results demonstrate, for the first time, that hypopharyngeal SCCs presenting high levels of HLTF have a worse prognosis. The quantitative determination of HLTF in hypopharyngeal SCCs was an independent prognostic marker alongside tumour node metastasis staging. HNSCCs expressed the truncated HLTF variant lacking the domains involved in DNA repair.

The helicase-like transcription factor (HLTF) belongs to the SWI/SNF family of proteins that use the energy from adenosine triphosphate hydrolysis to remodel chromatin during a variety of cellular processes. HLTF is also involved in DNA repair. Using computer-assisted microscopy, the immunohistochemical expression of HLTF was determined using a series of 100 hypopharyngeal and 56 laryngeal squamous cell carcinomas (SCCs) compared to tumor-free epithelia (60 cases) and dysplasias (92 cases). In hypopharyngeal SCC tumor progression, increased HLTF expression was associated with the percentage of immunopositive epithelial tissue areas (p=0.02) and the staining intensity of the positive area (p=0.0005). In the cases of laryngeal lesions, the immunolabeling intensity of HLTF significantly decreased with malignancy (p=0.01). We also observed a significant shift of HLTF expression from the cytoplasm toward the nuclear compartment (p=0.0007). Our data reveal an association between the presence of HLTF and neoplastic progression of hypopharyngeal and laryngeal SCCs.

Abstract. The enzymatic activity of matrix metalloproteinase-9 (MMP-9) suggests that its presence in hypopharyngeal and laryngeal squamous cell carcinomas (HSCCs, LSCCs) could have prognostic value. We tested this hypothesis by quantitative morphometric analysis of immunohistochemical staining in histological sections of 73 stage IV HSCCs and 45 LSCCs (30 cases of stage I/II, 15 cases of stage IV). As compared to tumour-free epithelium an increase for the labelling index in LSCCs reached statistical significance (p=0.04). Specimens of Reinke's edema were strongly higher in this parameter compared to tumour-free tissue area (p=0.000001), underscoring an association between the level of MMP-9 expression and inflammation. Focusing on patients' recurrence status we identified thresholds for the labelling index of 10% for HSCCs and 18% for LSCCs, both indicating rapid recurrence and dismal prognosis unless surpassed. When relating data for MMP-9 to those for three adhesion/growth-regulatory galectins, a positive correlation with galectin-7 expression was detected in LSCCs. This finding suggests a possible potential role of this endogenous lectin as inducer of MMP-9 gene expression in situ. Of note, galectin-1 expression was negatively correlated with and that of galectin-3, a substrate of MMP-9, not related. In conclusion our study delineated a prognostic role of MMP-9 immunodetection in high-stage HSCCs and in LSCCs when separating patients by a distinct threshold for the labelling index. Moreover, it indicated associations between MMP-9 and multifunctional galectins-1 and -7 in situ.