Silencing of heat shock factor 1 (HSF1) inhibits proliferation, invasion, and epithelial-mesenchymal transition in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma is characterized by high rates of morbidity and mortality. Evidence obtained for different types of cancer shows that tumor initiation, progression, and therapeutic resistance are regulated by heat shock factor 1. This research aimed to analyze the effects of heat shock factor 1 on the biological behavior of oral squamous cell carcinoma. METHODS: Clinicopathological and immunoexpression study of heat shock factor 1 in 70 cases of oral tongue SCC and functional assays by gene silencing of this factor in an oral tongue SCC cell line. RESULTS: Heat shock factor 1 was overexpressed in oral tongue SCC specimens compared to normal oral mucosa (p < 0.0001) and in the SCC15 line compared to immortalized keratinocytes (p < 0.005). No significant associations were observed between overexpression of heat shock factor 1 and clinicopathological parameters or survival rates of the oral tongue SCC cases in the present sample. In vitro experiments showed that heat shock factor 1 silencing inhibited cell proliferation (p < 0.005) and cell cycle progression, with the accumulation of cells in the G0/G1 phase (p < 0.01). In addition, heat shock factor 1 silencing reduced cell invasion capacity (p < 0.05) and epithelial-mesenchymal transition, characterized by a decrease in vimentin expression (p < 0.05) and an increase in E-cadherin expression (p < 0.001). CONCLUSION: Heat shock factor 1 may exert several functions that help maintain cell stability under the stressful conditions of the tumor microenvironment. Thus, strategies targeting the regulation of this protein may in the future be a useful therapeutic tool to control the progression of oral squamous cell carcinoma.

Teratocarcinoma-derived growth factor-1 (Cripto-1) is overexpressed in epithelial odontogenic lesions displaying more aggressive behaviour.

PURPOSE: Cripto-1 also known as teratoma-derived growth factor 1 (TDGF-1) belongs to the EGF-CFC family of growth factor-like molecules. Cripto-1 is involved with embryonic development and not expressed in adult tissue, but some tumours are accompanied by reactivation. METHODS: The aim of this study was to evaluate the immunohistochemical expression of Cripto-1 in most common odontogenic cysts and tumours. Thirty ameloblastomas, 30 keratocysts, 30 dentigerous cysts and two ameloblastic carcinomas were evaluated using the polymeric immunoperoxidase technique. Immunohistochemical expressions were analysed by the IRS (immunoreactive score). Statistical analyses were performed by the Kruskal-Wallis and Mann-Whitney tests (p ≤ 0.05). RESULTS: Age ranged from 9 to 75 years old, with a prevalence of females (n = 49/53.3%). The mandible was the most affected anatomical site (n = 69/75.0%). Cripto-1 immunoexpression was observed in all ameloblastoma, keratocyst and ameloblastic carcinoma cases, although nine dentigerous cyst cases (30%) were negative. Expression scores were higher in ameloblastoma, keratocyst and ameloblastic carcinoma cases (median ranging from 8 to 11) when compared with dentigerous cyst cases (median of 2), with a statistically significant difference (p < 0.001). CONCLUSIONS: Cripto-1 is critically important in the progression of several tumours since it is related to significant cell survival and differentiation pathways. The high expression of Cripto-1 in more aggressive odontogenic lesions suggests that this molecule may be involved in the activation of important pathways related to the etiopathogenesis of these lesions.

Peripheral compound odontoma: A rare case report and literature review.

Peripheral odontoma is a very rare odontogenic hamartoma arising in soft tissues. Here, we report a case of peripheral odontoma in a pediatric patient and review the cases published in the literature. An 11-year-old male patient presented a nodular lesion in the anterior region of the palate for over 1 year. Under the clinical hypothesis of fibroma, an excisional biopsy was performed. Histopathological examination revealed the presence of tooth-like structures, formed by enamel, and dentin matrix, occasionally associated with the dental papilla and surrounding pulp tissue, thus, the histopathological diagnosis of peripheral odontoma was established. The patient has been undergoing follow-up for 6 months without any signs of lesion recurrence. Peripheral odontomas are uncommon lesions that usually affect young patients and display a preference for the maxilla and limited growth potential. The recognition of the clinical and histopathological features of the peripheral odontoma is indispensable for the establishment of its diagnosis.

Oral benign neoplasms: A retrospective study of 790 patients over a 14-year period.

INTRODUCTION AND OBJECTIVE: Oral benign neoplasms (OBNs) exhibit some features that can guide the professionals to the correct diagnosis and best treatment. Through retrospective studies, medical records can be reviewed to better describe a given population and, furthermore, help clinicians in routine practice. In this context, the objective of this paper was to analyze the cases of OBNs of an oral pathology referral department, from 2003 to 2017, in order to better understand their epidemiological and clinicopathological characteristics. METHODS: A total of 8355 histopathological reports were analyzed. Lesions diagnosed as OBNs were selected and the following variables were recorded: gender, age, histological type of the lesion, anatomical location, rate and pattern of growth, type of base, color, symptomatology and diagnostic hypotheses on clinical examination. RESULTS: OBNs represented 9.4% of all lesions diagnosed. The most frequent histopathological types were fibroma (39.9%), papilloma (22%), fibroblastoma (13.1%), lipoma (10.2%) and hemangioma (6.1%). Overall, most cases affected females (n=518; 65.6%) and in the fifth decade of life (n=148; 18.7%). The oral mucosa was the most common site (n=265; 33.5%). The most common features of each OBN were also highlighted. CONCLUSION: The most common OBNs were fibroma, papilloma, fibroblastoma, lipoma and hemangioma. Overall, the OBN presented common clinical features; however, in particular cases, there are some characteristics that can lead the professionals to the correct diagnosis. Nevertheless, in general, histopathological analysis must be performed to confirm diagnosis. Intraosseous tumors and large lesions may require imaging tests to help diagnosis.

Cripto-1 is overexpressed in carcinoma ex pleomorphic adenoma of salivary gland.

INTRODUCTION: Cripto-1 is a member of the epidermal growth factor-Cripto-1/FRL-1/Cryptic family. Besides being critical for early embryonic development, Cripto-1 is also associated with the development and behavior of several cancers. OBJECTIVE: We analyzed the immunoexpression of Cripto-1 in normal salivary glands (NSGs), pleomorphic adenomas (PAs), and carcinoma ex pleomorphic adenomas (CaExPAs) of salivary glands. METHODS: A total of 12 NSGs, 16 PAs and 12 CaExPAs underwent immunohistochemical study by the polymeric biotin-free technique. Immunopositive cells were evaluated semiquantitatively (scores 0-3). For statistical analysis, Mann-Whitney and Kruskal-Wallis tests were performed and a significance level of p ≤ 0.05 was established. RESULTS: Most CaExPAs (n = 10) were strong positive (score 3) for Cripto-1, and only three cases of PAs and two specimens of NSGs exhibited some expression (score 1), being statistically significant these findings (p < 0.001). No difference between the expression of this protein in tumors of major and minor salivary glands was observed. Overexpression was found mainly in cases of CaExPAs with invasive growth (n = 8) when compared to those without capsular invasion (intracapsular pattern) (p = 0.036). Patients with or without lymph node metastasis showed no difference (p = 0.294). CONCLUSION: The results revealed a significantly higher expression of Cripto-1 in CaExPA compared to PA and NSG, suggesting this protein is possibly deregulated in PA malignant transformation. Furthermore, the increased expression of this protein is associated with a more aggressive behavior (invasive growth) in salivary gland tumors.

Central mucoepidermoid carcinoma radiographically mimicking an odontogenic tumor: A case report and literature review.

Central mucoepidermoid carcinoma (CMC) of the jaw bones is a rare malignant salivary gland tumor of unknown pathogenesis, comprising about 4% of all mucoepidermoid carcinomas (MECs). Most cases are histologically classified as a low-grade tumor and radiographically appear as a well-defined unilocular or multilocular radiolucent lesion. Block resection or wide local excisions are the treatment of choice and patients usually show a good overall prognosis although a long-term follow-up is necessary. This report describes a case of a 28-year-old male with MEC in the posterior region of the mandible and discusses its clinical, radiographic and histopathological findings. Although rare, CMC may be considered a differential diagnosis in cases of proliferative and osteolytic lesions in the oral cavity even when its clinical and/or radiographic findings do not suggest malignancy.