Hélder Antônio Rebelo Pontes

Immunoexpression of Ki67, proliferative cell nuclear antigen, and Bcl-2 proteins in a case of ameloblastic fibrosarcoma.

Ameloblastic fibrosarcoma (AFS), regarded as the malignant counterpart of the benign ameloblastic fibroma, is an extremely rare odontogenic neoplasm with only 68 cases reported in the English literature up to 2009. It is composed of a benign odontogenic epithelium, resembling that of ameloblastoma, and a malignant mesenchymal part exhibiting features of fibrosarcoma. Due to the rarity of the lesion, little is known about its molecular pathogenesis; therefore, in the current study, we sought to evaluate the immunoexpression of Ki67, proliferative cell nuclear antigen, and Bcl-2 proteins in AFS, comparing the results obtained with its benign counterpart, as well as to report a new case of this rare entity affecting a 19-year-old female patient. The results obtained revealed that all the proteins evaluated were overexpressed in the malignant mesenchymal portion of AFS if compared with ameloblastic fibroma, suggesting that nuclear proliferative factors such as Ki67 and proliferative cell nuclear antigen, in association to histopathologic features, may be useful markers for identifying the malignancy and that, despite the lack of molecular analysis in the case reported, Bcl-2 alteration may play a role in AFS pathogenesis.

Report of four cases of Ameloblastic fibro-odontoma in mandible and discussion of the literature about the treatment

The ameloblastic fibro-odontoma is defined as a tumour with the general features of the ameloblastic fibroma but that also contains enamel and dentine. AFO normally presents as a painless swelling in the posterior portion of the maxilla or mandible. Radiographs show a well-defined radiolucent area containing various amounts of radiopaque material of irregular size and form. The most appropriate treatment for a large AFO has not been completely determined. This paper reports four large AFO cases and reviews the relevant literature regarding the clinical and surgical features of this lesion.

Clinicopathological analysis of head and neck chondrosarcoma: three case reports and literature review

Chondrosarcoma (CHS) is a malignant neoplasm characterized by the formation of cartilaginous matrix by neoplastic cells, with a high propensity for local recurrences. Head and neck CHS is rare, accounting for less than 12% of all cases of CHS, usually affecting the maxilla. The majority of affected patients are in the fourth decade of life, with a slight predilection for male patients. A painless swelling is commonly the most frequent complaint. Surgery with wide en-bloc resection is the preferred treatment for CHS; radiotherapy and chemotherapy are usually palliative options. Owing to its rarity, there are few clinical series evaluating the biological behaviour of head and neck CHS. The aim of this study is to analyse the clinicopathological characteristics of head and neck CHS by reporting 3 new cases of this neoplasia affecting the jaw bones and reviewing the clinical series previously published in the English literature.

Nuclear factor κB and cyclooxygenase-2 immunoexpression in oral dysplasia and oral squamous cell carcinoma

Oral leukoplakia is the main potentially malignant oral lesion, and oral squamous cell carcinoma accounts for more than 95% of all malignant neoplasms in the oral cavity. Therefore, the aim of this study was to verify the immunoexpression of nuclear factor κB (NF-κB) and cyclooxygenase-2 (COX-2) proteins in dysplastic oral lesions and oral squamous cell carcinoma. Immunohistochemical reactions were performed on 6 inflammatory fibrous hyperplasia, 28 oral leukoplakia, and 15 oral squamous cell carcinoma paraffin-embedded samples. Immunoperoxidase reaction for NF-κB and COX-2 was applied on the specimens, and the positivity of the reactions was calculated for 1000 epithelial cells. Using the analysis of variance and the Tukey post hoc statistical analyses, a significantly increased immunoexpression for NF-κB was observed when oral squamous cell carcinoma samples were compared with the other groups studied. However, using the Kruskal-Wallis and the Dunn post hoc tests, a statistically significant result for COX-2 expression was obtained only when the moderate dysplasia group was compared with the inflammatory fibrous hyperplasia group. Nuclear factor κB may participate in the malignant phenotype acquisition process of the oral squamous cell carcinoma in its late stages, whereas COX-2 may be involved in the early stages of oral carcinogenesis process.

E-cadherin downregulation and Twist overexpression since early stages of oral carcinogenesis.

There is some evidence of Twist participation in oral carcinogenesis; however, little is known about its interaction with E-cadherin in oral squamous cell carcinoma (OSCC) development. This experimental study included an immunohistochemical analysis of Twist and E-cadherin proteins in paraffin-embedded specimens of oral leukoplakia (OL), OSCC, and normal oral mucosa. In addition, it was also performed a Western blot and double-immunofluorescence analysis of Twist and E-cadherin expression in OSCC cell lines. Significant differences in Twist and E-cadherin immunoexpression were observed between normal oral mucosa and OL, with an inverse relation since the earliest stages of oral dysplasia (r = -0,512; P < 0.001). Western blot and double-immunofluorescence analysis showed differences in Twist and E-cadherin expression among human oral keratinocytes and OSCC cell lines suggesting that downregulation of E-cadherin occurs in a dependent manner of Twist in OSCC. Our results showed a possible value of Twist and E-cadherin in the prediction of risk of oral epithelium malignant transformation.

Squamous Cell Carcinoma of the Tongue and Floor of the Mouth: Analysis of Survival Rate and Independent Prognostic Factors in the Amazon Region

Oral squamous cell carcinoma (OSCC) accounts for more than 95% of all malignant neoplasms in the oral cavity. Although several studies have shown the epidemiology of this cancer in Brazil, there do not seem to be any studies that describe the prognostic factors related to OSCC in the Amazon region. Therefore, the aim of this study was to determine the survival rate and prognostic significance of different factors in patients from this region affected by OSCC. Data from 85 patients with histologically confirmed squamous cell carcinoma of the tongue and floor of the mouth identified from the Ofir Loyola Hospital archives were collected and analyzed using univariate (log-rank test) and multivariate (Cox proportional hazard model) tests. The overall 5-year survival rate was found to be 27%. Univariate analysis showed that the 5-year survival rate was significantly higher for younger (≤45 y) female patients, patients with T1-2 tumors and clinically clear neck nodes (N0), patients with early stage cancers (AJCC stage I-II), and patients treated with surgical procedures. However, multivariate analysis showed that the 5-year survival rate was significantly higher only in the younger patients and those who underwent surgical treatment. The age of the patient at the moment of diagnosis and treatment with surgical procedures were the only independent prognostic factors that affected the 5-year survival rate of the patients in this region.

MCM3 could be a better marker than Ki‐67 for evaluation of dysplastic oral lesions: an immunohistochemical study

BACKGROUND The aim of this study was to identify the expression of MCM3, Ki-67 and p27 in normal mucosa, leucoplakia and oral squamous cell carcinoma (OSCC) and determine whether altered expression could serve as a prognostic marker of a malignant progression of dysplastic lesions. METHODS The samples were collected from 37 patients with oral leucoplakia (13 with mild dysplasia - MLD, 12 with moderate dysplasia - MD and 12 with severe dysplasia - SD). Eleven samples of mouth floor mucocele (M) and 50 floor mouth and tongue samples OSCC of untreated patients were included in this study. Immunohistochemical expression of MCM3, Ki-67 and p27 of all the groups was analysed. Kruskal-Wallis and Dunns test were used to determine differences among groups, and a Pearsons correlation test was used to evaluate the correlation between the proteins. RESULTS Ki-67 expression was higher in OSCC than M (P < 0.001) and MLD (P < 0.01) groups, and there was a lower expression in M compared with MD and SD (P < 0.05). Regarding p27, its expression was lower in OSCC compared with M, MD and SD. MCM3 expression was lower in M compared with SD and OSCC (P < 0.001), and MLD showed a lower expression when compared SD (P < 0.01) and OSCC (P < 0.001). Moreover, a better correlation was observed between the proteins MCM3 and p27 than between Ki-67 and p27 proteins when all lesions were examined together. CONCLUSIONS This study showed that MCM3 could be a better marker than Ki-67 for evaluation of dysplastic oral lesions.

P63 expression in papillary cystadenoma and mucoepidermoid carcinoma of minor salivary glands

OBJECTIVE The aim of this study was to investigate the expression of p63 protein in mucoepidermoid carcinoma and papillary cystadenoma of the salivary glands, and to evaluate the usefulness of this protein in distinguishing these tumors. STUDY DESIGN Immunoexpression of p63 protein was studied and quantified in 9 formalin-fixed paraffin-embedded mucous retention cysts, 4 papillary cystadenomas, and 19 low-grade and 9 high-grade mucoepidermoid carcinomas. RESULTS All cases were positive for p63 immunoexpression; however, it was observed that p63 labeling in mucous retention cysts and papillary cystadenomas was limited to the basal layers of the cystic spaces, whereas in low-grade mucoepidermoid carcinomas, positive nuclear staining was also found diffusely in the suprabasal layers. Mucoepidermoid carcinoma presented increased immunoexpression of p63 compared with the other groups. CONCLUSIONS P63 immunohistochemical expression pattern can be helpful in distinguishing low-grade mucoepidermoid carcinoma from papillary cystadenoma of the salivary glands.

Ameloblastic carcinoma (secondary type) with extensive squamous differentiation areas and dedifferentiated regions

Ameloblastic carcinoma is rare, accounting for 1.5%-2.0% of all odontogenic tumors. Few small series are available, but data on its clinicopathologic characteristics derive mainly from single case reports; therefore, descriptions of new cases may help to better understand the biological characteristics of this rare odontogenic malignancy. In the current report we describe an ameloblastic carcinoma affecting a 27-year-old female patient who had a previous diagnosis of ameloblastoma 7 years before. The carcinoma featured extensive areas of squamous differentiation resembling a primary intraosseous squamous cell carcinoma, as well as areas of dedifferentiation, a poorly documented histologic characteristic of ameloblastic carcinoma. This case provides new insights on the microscopic spectrum of ameloblastic carcinoma, permitting a critical discussion of the current World Health Organization classification of this odontogenic tumor.

Mismatch repair system proteins in oral benign and malignant lesions

Different environmental agents may cause DNA mutations by disrupting its double-strand structure; however, even normal DNA polymerase function may synthesize mismatch nucleotide bases, occasionally demonstrating failure in its proofreading activity. To overcome this issue, mismatch repair (MMR) system, a group of proteins specialized in finding mispairing bases and small loops of insertion or deletion, works to avoid the occurrence of mutations that could ultimately lead to innumerous human diseases. In the last decades, the role of MMR proteins in oral carcinogenesis and in the development of other oral cavity neoplasms has grown, but their importance in the pathogenesis and their prognostic potential for patients affected by oral malignancies, especially oral squamous cell carcinoma (OSCC), remain unclear. Therefore, in this manuscript we aimed to review and critically discuss the currently available data on MMR proteins expression in oral potentially malignant lesions, in OSCC, and in other oral neoplasms to better understand their relevance in these lesions.