The incidence of head and neck cancer (HNC), constituting approximately one in ten cancer cases worldwide, affects approximately 644,000 individuals annually. Managing this complex disease involves various treatment modalities such as systemic therapy, radiation, and surgery, particularly for patients with locally advanced disease. HNC treatment necessitates a multidisciplinary approach due to alterations in patients’ genomes affecting their functionality. Predominantly, squamous cell carcinomas (SCCs), the majority of HNCs, arise from the upper aerodigestive tract epithelium. The epidemiology, staging, diagnosis, and management techniques of head and neck squamous cell carcinoma (HNSCC), encompassing clinical, image-based, histopathological and molecular profiling, have been extensively reviewed. Lymph node metastasis (LNM) is a well-known predictive factor for HNSCC that initiates metastasis and significantly impacts HNSCC prognosis. Distant metastasis (DM) in HNSCC has been correlated to aberrant expression of cancer cell-derived cytokines and growth factors triggering abnormal activation of several signaling pathways that boost cancer cell aggressiveness. Recent advances in genetic profiling, understanding tumor microenvironment, oligometastatic disease, and immunotherapy have revolutionized treatment strategies and disease control. Future research may leverage genomics and proteomics to identify biomarkers aiding individualized HNSCC treatment. Understanding the molecular basis, genetic landscape, atypical signaling pathways, and tumor microenvironment have enhanced the comprehension of HNSCC molecular etiology. This critical review sheds light on regional and distant metastases in HNSCC, presenting major clinical and laboratory features, predictive biomarkers, and available therapeutic approaches.

To co-evaluate topoisomerase IIa (Topo IIa) protein expression and gene status in pancreatic ductal adenocarcinoma, determining the potential prognostic impact of its alterations. Using tissue microarrays, 50 sporadic, primary pancreatic ductal adenocarcinomas were cored twice and re-embedded into one paraffin block with a core diameter of 1 mm. Immunohistochemistry and chromogenic in situ hybridization were performed in serial tissue sections for the detection of protein expression levels, chromosome 17 and Topo IIa gene status, respectively. Finally using a semi-automated image analysis system we evaluated the levels of protein expression. A significant proportion of the tumors showed Topo IIa overexpression (32/50 or 64%). Gene amplification and deletion were detected in 9 and 4 cases, respectively, associated with protein overexpression. Aneuploidy regarding chromosome 17 was observed in 19/50 tumors and correlated with poor survival rate (Cox regression test: p = 0.001). Topo IIa protein expression was strongly correlated with stage (p = 0.021) and grade (p = 0.034). Topo IIa gene amplification correlates with protein overexpression, but not vice versa. This is a crucial observation for the application of targeted chemotherapies, such as anthracyclines, only in subgroups of patients, according to molecular deregulation criteria and not only to immunohistochemical results. Also, chromosome 17 and not Topo IIa gene instability can be used as a potential independent prognostic factor.

Aims: To investigate the potential role of caspase-3 and caspase-8 protein expression in the biological behaviour of tongue squamous cell carcinoma.Materials and methods: We conducted immunohistochemical analyses of 87 specimens of primary tongue squamous cell carcinoma, using monoclonal anti-caspase-3 and anti-caspase-8 antibodies. A digital image analysis assay was also performed in order to evaluate the results.Results: Reduced expression of caspase-8 and -3 proteins was observed in 30/87 (34.5 per cent) and 79/87 (90.5 per cent) cases, respectively. Cox regression analysis showed no prognostic significance for the association between overall protein expression of either marker and survival probability (p = 0.174 for caspase-3; p = 0.608 for caspase-8). Interestingly, the size of the examined tumours was strongly correlated with survival status (p = 0.024).Conclusions: Simultaneous deregulation of caspase-8 and -3 is a frequent event in tongue squamous cell carcinoma. Activation of caspase-3, which is predominantly down-regulated, may be a crucial process for induction of apoptosis and response to therapeutic strategies.