Abnormal expression of bcl-2 and bax in rat tongue mucosa during the development of squamous cell carcinoma induced by 4-nitroquinoline 1-oxide

4-Nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis is a useful model for studying oral squamous cell carcinoma. The aim of this study was to investigate the expression of bcl-2 and bax during tongue carcinogenesis induced by 4NQO. Male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution through their drinking water for 4, 12 or 20 weeks. Ten animals were used as negative control. Although no histological changes were induced in the epithelium after 4 weeks of carcinogen exposure, bcl-2 and bax were over-expressed (P < 0.01) in all layers of the 'normal' epithelium. The expression levels were the same in all layers of epithelium for both the antibodies used (bcl-2 or bax). In dysplastic lesions at 12 weeks following carcinogen administration, the levels of bcl-2 and bax expression did not increase when compared to negative control with the immunoreactivity for bcl-2 being restricted to the superficial layer of epithelium. In well-differentiated squamous cell carcinoma induced after 20 weeks of treatment with 4NQO, bcl-2 was expressed in some cells of tumour islands. on the other hand, immunostaining for bax was widely observed at the tumour nests. The labelling index for bcl-2 and bax showed an increase (P < 0.05) after only 4 weeks of 4NQO administration. In conclusion, our results suggest that abnormalities in the apoptosis pathways are associated with the development of persistent clones of mutated-epithelial cells in the oral mucosa. Bcl-2 and bax expression appears to be associated with a risk factor in the progression of oral cancer.

Detection of HPV in mouth floor squamous cell carcinoma and its correlation with clinicopathologic variables, risk factors and survival

The human papillomavirus (HPV) has been historically associated with head and neck cancers, although its role in oral carcinogenesis remains poorly defined. The purpose of this study was to investigate the prevalence of HPV in mouth floor squamous cell carcinoma and correlate it with clinicopathologic variables, risk factors and survival. HPV presence was evaluated by nested polymerase chain reaction (nPCR) in 29 paraffin-embedded specimens of mouth floor squamous cell carcinoma. HPV DNA was detected in 17.2% (5 of 29) of the specimens; the highest prevalence was observed in non-smoking patients over the age of 60 years. All HPV DNA positive specimens were detected in men with clinical stage III and IV lesions, being most of which were moderately differentiated. Despite this correlation there were no statistically significant differences observed among the analyzed variables, including patients' survival. The relatively low incidence of HPV DNA present in these tumors suggests that this virus does not, by itself, have a significant role in the development of mouth floor squamous cell carcinoma. J Oral Pathol Med (2008) 37: 593-598

Cholangiocarcinoma and Squamous Cell Carcinoma of the Stratified Epithelial Portion of the Stomach in a Horse: A Case Report

Both cholangiocarcinoma and squamous cell carcinoma of the stomach stratified squamous epithelial portion are rarely found in equine medicine despite being more common in human beings, dogs, and cats. The objective of the present article was to report the simultaneous occurrences of these two types of neoplasias in an 11-year-old mare. Numerous firm, whitish nodules were distributed throughout the liver parenchyma and those protruding over its surface were umbilicated in their appearance. It was verified that the nodules adhered to the peritoneum and omentum, diaphragm, spleen, and stomach serosa compressed the adjacent structures. The stomach stratified squamous epithelial portion, particularly originating in the margo plicatus toward the cardia, was covered by numerous smooth, whitish spherules. Microscopic examination allowed the liver, tumor, and the abdominal implants to be identified as a cholangiocarcinoma, and the stomach neoplasia as a carcinoma of its stratified squamous epithelial portion. Considering this as an uncommon finding, although when considered individually, the presence of a cholangiocarcinoma and a squamous cell carcinoma of the stratified squamous epithelial portion of the equine stomach in the same specimen is worthy of reporting. (C) 2011 Elsevier B.V. All rights reserved.

Squamous cell carcinoma in a residual mandibular cyst

Described is a case of squamous-cell carcinoma arising in a residual cyst in a 60-year-old edentulous woman. The clinical and radiographic diagnosis was residual cyst, and the treatment employed was conservative surgical enucleation. The cause of these changes is unknown. Theoretically, the inflammatory reaction may have been a predisposing factor.

Homeobox gene expression profile indicates HOXA5 as a candidate prognostic marker in oral squamous cell carcinoma

The search for molecular markers to improve diagnosis, individualize treatment and predict behavior of tumors has been the focus of several studies. This study aimed to analyze homeobox gene expression profile in oral squamous cell carcinoma (OSCC) as well as to investigate whether some of these genes are relevant molecular markers of prognosis and/or tumor aggressiveness. Homeobox gene expression levels were assessed by microarrays and qRT-PCR in OSCC tissues and adjacent non-cancerous matched tissues (margin), as well as in OSCC cell lines. Analysis of microarray data revealed the expression of 147 homeobox genes, including one set of six at least 2-fold up-regulated, and another set of 34 at least 2-fold down-regulated homeobox genes in OSCC. After qRT-PCR assays, the three most up-regulated homeobox genes (HOXA5, HOXD10 and HOXD11) revealed higher and statistically significant expression levels in OSCC samples when compared to margins. Patients presenting lower expression of HOXA5 had poorer prognosis compared to those with higher expression (P=0.03). Additionally, the status of HOXA5, HOXD10 and HOXD11 expression levels in OSCC cell lines also showed a significant up-regulation when compared to normal oral keratinocytes. Results confirm the presence of three significantly upregulated (>4-fold) homeobox genes (HOXA5, HOXD10 and HOXD11) in OSCC that may play a significant role in the pathogenesis of these tumors. Moreover, since lower levels of HOXA5 predict poor prognosis, this gene may be a novel candidate for development of therapeutic strategies in OSCC.

Unusual presentation of oral squamous cell carcinoma in a young woman

Oral squamous cell carcinoma (OSCC) is the most common oral malignant neoplasm, mainly affecting individuals over 50 years old with a history of tobacco and alcohol use. The occurrence of this oral cancer in individuals under 40 years old is unusual and, when it does occur, shows a weaker relation to those risk factors and a more aggressive clinical course. Due to the paucity of reports in this population, it is difficult to prove its increasing trend. A case of oral squamous cell carcinoma in a 39-year-old woman with no history of tobacco or alcohol use is reported. Clinical and histopathological findings, aetiology, and treatment are discussed. The increasing trend of oral squamous cell carcinoma in young women without known risk factors highlights the need for clinicians to be prepared to diagnose this lesion quickly and precisely, providing a better prognosis, chance of survival, and quality of life for the patient.

The expression of chemokines CCL19, CCL21 and their receptor CCR7 in oral squamous cell carcinoma and its relevance to cervical lymph node metastasis

The purpose of this study is to determine the expression of CCL19, CCL21, and CCR7 in samples of oral squamous cell carcinoma (OSCC) and their relationship with clinical and microscopic parameters. A comparative analysis was made of the mRNA expression of these chemokines and receptor in OSCC and normal oral mucosa. The immunoexpression of CCR7, CCL19, and CCL21 was also verified in OSCC and lymph nodes. Statistical significance was accepted at P < 0.05. Similar levels of CCR7, CCL19, and CCL21 mRNA in OSCC and normal oral mucosa were seen. A low expression of CCL19 and CCL21 in the intra- and peritumoral regions was observed. Scarce CCL19+ and CCL21+ cells were also noted in metastatic and non-metastatic lymph nodes. No association was found between the expression of these chemokines and clinical and microscopic parameters. Our findings would suggest that CCL19 and CCL21 may not be associated with cervical lymph node metastasis or other clinical and microscopic factors in OSCC. © 2012 International Society of Oncology and BioMarkers (ISOBM).

Tumor-associated macrophages and the profile of inflammatory cytokines in oral squamous cell carcinoma

Objective: To evaluate and characterize macrophage populations (M1/M2) in the tumor microenvironment of oral cavity squamous cell carcinoma (OCSCC). The relationship between macrophages and clinicopathological factors, such as survival data, lymph node metastasis, tumoral proliferation, and WHO histological grading are also analyzed. Materials and methods: The samples consisted of surgically excised specimens from patients with non-metastatic and metastatic OCSCC and normal oral mucosa (control). Immunohistochemistry, flow cytometry, and qRT-PCR were used to evaluate macrophage populations and the expression of pro- (IL-12, IL-23, and INF-γ) and anti-inflammatory (IL-10 and TGF-β) cytokines. The level required for statistical significance was defined as p < 0.05. Results: The data showed a predominance of M2 phenotype (high percentage of IL-10+TGF-β+) macrophages in the tumor microenvironment of OCSCC. A higher percentage of macrophages expressing TGF-β was seen in the OCSCC group when compared with healthy individuals. The assessment of mRNA expression also presented a greater expression of anti-inflammatory cytokines TGFβ and IL10 in OCSCC when compared with the control group. The percentage of macrophages, demonstrated by immunohistochemistry, was significantly higher in the metastatic OCSCC group than in the non-metastatic and control groups. The log-rank test also showed that the mean survival time for patients with high levels of macrophages was less (44 months) when compared with patients with a low percentage of such cells (93 months). Conclusion: A predominance of the M2 phenotype in the tumor microenvironment of OCSCC could contribute to local immunosuppression, via TGF-β production, and consequently greater lymph node involvement and reduced patient survival time. © 2012 Elsevier Ltd. All rights reserved.