Prognostic Significance of Histopathological Parameters for Salivary Gland Adenoid Cystic Carcinoma.

Adenoid cystic carcinoma (ACC) is a rare salivary gland tumor that accounts for approximately 1% of all head and neck cancers. Despite its initial indolent behavior, long-term survival is poor due to locoregional recurrence in approximately 40% and distant metastasis in up to 60% of patients who undergo radical treatment. The histological parameters of ACC and the combination of these parameters in histopathological grading systems provide valuable prognostic information about the clinical course of the disease. Within this context, this review aims to analyze the impact of histopathological parameters, individual or combined in histopathological grading systems of malignancy, on ACC prognosis. Individual histopathological parameters such as solid pattern, presence of tumor necrosis, high-grade transformation, dominance of the epithelial component, presence of perineural and lymphovascular invasion, and positive surgical margins have negative impacts on the survival of patients with ACC. There are currently four histopathological grading systems for ACC; however, few studies have validated these systems and most of them explored small cohorts with short follow-up. Considering that the application of grading systems has been associated with ACC prognosis, a broader validation will allow not only their use for prognostic prediction but also assist in treatment planning.

A Systematic Review of Adenoid Ameloblastoma: A Newly Recognized Entity.

BACKGROUND: Recently, a new odontogenic tumor has been described, the so-called adenoid ameloblastoma (AdAM). The aim of this review was to determine the clinical and imaging features of AdAM and to describe its main histopathological findings. METHODS: The systematic review included published cases with a diagnosis of AdAM in the gnathic bones, which had sufficient clinical, imaging, and histopathological data to confirm its diagnosis. The following histopathological diagnostic criteria were adopted: presence of ameloblastoma-like components, duct-like structures, spiral cellular condensations, and a cribriform architecture. RESULTS: Fifteen articles, corresponding to 30 cases of AdAM, were selected. Most cases affected men (63.3%), with a slight preference for the mandible (16:14) and the posterior region of gnathic bones was the most commonly affected site. The mean age at diagnosis was 40.8 years. Clinically, the lesions usually presented as a swelling (53.3%) and, radiographically, as a well-defined radiolucency (33.4%). Surgical resection (40%) was the most frequently adopted treatment and recurrence occurred in 30% of cases. Microscopic examination showed cribriform areas in most AdAM cases (93.3%); duct-like structures and spiral cellular condensations were seen in 100% of the cases. CONCLUSION: The small number of reported cases, the existence of erroneous diagnoses, and the adoption of initial conservative management make it difficult to determine whether AdAM has a higher risk of recurrence or more aggressive biological behavior than conventional ameloblastomas.

TWIST1 regulates proliferation, migration, and invasion and is a prognostic marker for oral tongue squamous cell carcinoma.

BACKGROUND: Epithelial-mesenchymal transition is one of the main mechanisms for tumor progression and metastasis. Transcription factors such as TWIST1 are key regulators of the epithelial-mesenchymal transition and are regarded as potential therapeutic targets for the treatment of cancer. The purpose of this study was to examine TWIST1 as a possible epithelial-mesenchymal transition-related prognostic biomarker in oral epithelial dysplasia and oral tongue squamous cell carcinomas, as well as the biological behavior of TWIST1-silencing in oral tongue squamous cell carcinomas cell lines. METHODS: Immunohistochemical analysis of TWIST1, E-cadherin, and N-cadherin was carried out in 47 samples representing oral epithelial dysplasia and 41 oral tongue squamous cell carcinomas. The suppression of TWIST1 expression was performed using shRNA-expression vectors in HSC-3 and SCC-9 cells to investigate in vitro the impact of TWIST1 on proliferation, apoptosis, viability, migration, and invasion of SCC-9 and HSC-3 cells. RESULTS: The expression of nuclear TWIST1 was significantly higher in oral tongue squamous cell carcinomas than in oral epithelial dysplasis (p < 0.0001), whereas TWIST1 in the cytoplasm was more expressed in oral epithelial dysplasis (p = 0.012). The high cytoplasmic expression of TWIST1 was significantly associated with shortened overall survival (p < 0.05), and increased nuclear TWIST1 expression was significantly related to high risk of recurrence (p = 0.03). Knockdown of TWIST1 in oral tongue squamous cell carcinomas cells induced the expression of E-cadherin and inhibited N-cadherin, which were followed by decreased proliferation, migration, and invasion. CONCLUSIONS: Our research suggests that TWIST1 is linked to the development of oral tongue carcinogenesis and may be used as a prognostic indicator and therapeutic target for oral tongue squamous cell carcinomas patients.

Epithelial-mesenchymal transition modulates lower lip carcinogenesis and promotes cancer progression.

OBJECTIVE: To investigate and compare the immunoexpression of E-cadherin, α-SMA, TGF-ß and Snail proteins between cases of actinic cheilitis (AC) and squamous cell carcinoma of the lower lip (LLSCC). STUDY DESIGN: E-cadherin, α-SMA, TGF-ß and Snail antibody immunostaining was analyzed semiquantitatively in 54 AC cases and in 49 LLSCCs. The cases were classified as low and high expression for analysis of the association with clinicopathological variables and overall survival (OS) and disease-free survival (DFS) rates. RESULTS: High expression of E-cadherin (cytoplasmic) (p = 0.001) and α-SMA (p < 0.001) was identified in LLSCCs, as well as low expression of TGF-ß in LLSCCs (p < 0.001) and high expression of Snail in AC cases (p = 0.006). Survival analysis revealed that high expression of α-SMA at the tumor invasion front, a network immunostaining pattern of this protein, and high expression of TGF-ß in tumor buds were significantly associated with poor OS (p < 0.05). There was a higher risk of death among LLSCC cases with high expression of α-SMA (HR = 5.90, p = 0.03). High expression of TGF-ß in tumor buds was significantly associated with poor DFS (p = 0.007) and with a higher risk of negative outcomes for DFS (HR = 4.44, p = 0.014). CONCLUSIONS: The present results suggest the potential involvement of dysregulation of proteins associated with epithelial-mesenchymal transition in the modulation of lip carcinogenesis and greater aggressiveness of LLSCC.

Primary Intraosseous Squamous Cell Carcinoma Involving the Jaw Bones: A Systematic Review and Update.

Primary intraosseous oral squamous cell carcinoma (PIOSCC) is a rare malignant neoplasm that affects the jaws. Despite its aggressive biological behavior, there are no studies that evaluated the clinicopathological features of this tumor and parameters associated with its prognosis. The objective of the present study was to conduct a systematic review of the available data on oral and maxillofacial PIOSCC in order to determine its clinicopathological characteristics and biological behavior. We conducted a systematic review in May 2020 in multiple databases using a specific search strategy. Cases diagnosed as PIOSCC in the oral cavity and maxillofacial complex that had sufficient histopathological data, absence of ulceration in the oral mucosa, a negative result for a distant primary tumor, and radiographic evidence of an osteolytic lesion that was entirely or mostly surrounded by the jaw bones were included. A total of 109 published articles were included in our systematic review, corresponding to 257 cases. PIOSCC showed a male predilection (69.3%) and a preference for the mandible (7:1), with the posterior region being the most commonly affected site. The mean age at diagnosis was 57.3 years. Cortical expansion, pain, and lip/facial paresthesia were the most common clinical features. Regarding histopathological features, most PIOSCC were well-differentiated and the solid subtype was the most common. Statistical analysis showed that PIOSCC located in the mandible (p = 0.03) and recurrence (p < 0.01) were significantly associated with a higher mortality rate. PIOSCC has a poor prognosis, with high rates of mortality.

Biological role of epithelial-mesenchymal-transition-inducing transcription factors in head and neck squamous cell carcinoma: A systematic review.

OBJECTIVE: The aim of this systematic review was to explore the biological functions and mechanisms of epithelial-mesenchymal transition-inducing transcription factors in head and neck squamous cell carcinoma-derived cell lines. In addition, we analyzed the possible usefulness of epithelial-mesenchymal transition-inducing transcription factors as a future therapeutic target. DESIGN: An electronic search was performed in EMBASE, Medline/PubMed, Chinese BioMedical Literature Databases, and Cochrane Collaboration Library. Articles evaluating the relationship between epithelial-mesenchymal transition-inducing transcription factors and the biological behavior of head and neck squamous cell carcinoma cell lines were selected for this systematic review. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. RESULTS: After application of the previously established inclusion/exclusion criteria, 23 articles were included in the qualitative synthesis. Our study showed that epithelial-mesenchymal transition-inducing transcription factors are essential components during the progression of head and neck squamous cell carcinomas and their overexpression is associated with a greater capacity of dissemination and survival of the tumor and resistance to cancer treatment. The inhibition of epithelial-mesenchymal transition-inducing transcription factors is able to reverse the epithelial-mesenchymal transition process and to increase the sensitivity of head and neck squamous cell carcinoma cell lines to radio/chemotherapy. CONCLUSIONS: Analysis of the expression of epithelial-mesenchymal transition-inducing transcription factors for the prediction of prognosis and response to cancer treatment may have a significant clinical impact.