Márcia Cristina da Costa Miguel

Clinicopathological prognostic factors of oral tongue squamous cell carcinoma: A retrospective study of 202 cases

Although several histopathological parameters and grading systems have been described as predictive of the treatment response and outcome of oral squamous cell carcinoma (OSCC), none is universally accepted. A new scoring system, the histological risk model, was recently described to be a powerful predictive tool for recurrence and overall survival in OSCC. The aim of this study was to verify the predictive role of the histological risk model in a cohort of 202 patients at all stages of oral/mobile tongue squamous cell carcinoma (OTSCC). Demographic and clinical data were collected from the medical records and the tumours were evaluated using the histological risk model. Statistical analyses were performed using the χ(2) test, the Kaplan-Meier method, and the Cox regression model. The histological risk model showed no statistical correlation with demographic or clinical parameters and did not Predict the outcome of the OTSCC patients. However, multivariate regression analysis revealed a significant correlation of the clinical disease stage with the disease outcome. Despite major efforts to identify new predictive parameters and histological systems, clinical features are still the most reliable prognostic factors for patients with OTSCC.

Activin A immunoexpression as predictor of occult lymph node metastasis and overall survival in oral tongue squamous cell carcinoma.

The presence of regional lymph node metastasis has an important impact on clinical management and prognostication of patients with oral tongue squamous cell carcinoma (SCC). Approximately 30% to 50% of patients with oral tongue SCC have regional metastasis at diagnosis, but the limited sensibility of the current diagnostic methods used for neck staging does not allow detection of all cases, leaving a significant number of undiagnosed metastasis (occult lymph node metastasis). In this study, we evaluated whether clinicopathologic features and immunohistochemical detection of carcinoma‐associated fibroblasts (CAFs) and activin A could be predictive markers for occult lymph node metastasis in oral tongue SCC.

Epidemiology and correlation of the clinicopathological features in oral epithelial dysplasia: analysis of 173 cases

Oral epithelial dysplasias (OEDs) are potentially malignant disorders characterized by diverse degrees of cellular atypia. The early and careful diagnosis has extreme importance, allowing prevention of the progression to the oral squamous cell carcinoma. This study aimed to determine the epidemiology and then correlate it with the clinicopathological features of OED. One hundred seventy-three cases of oral lesions retrieved from the files of a Service of Pathological Anatomy, covering a 38-year period, were submitted to descriptive statistical analysis through the Pearson χ(2) test. The majority of cases were from affected females (57.9%), with a peak of occurrence in the age group of 41 and 55 years (37.3%), white patients (64.8%), and those with lesions located on the gingiva/alveolar ridge (25.1%). The lesions predominantly presented with white color (56.8%) and were described as nodules (27.4%), with a rough surface (76.7%), an exophytic growth (79.1%), and a sessile base (95.6%). The majority of the lesions with degree of mild (34.6%) and moderate (34.9%) OED had clinical diagnosis of leukoplakia, whereas 33.3% of the lesions with degree of severe had clinical diagnosis of squamous cell carcinoma (P < .05). Tobacco use was the risk habit more related with OED (42.6%) (P > .05). The knowledge of OED epidemiology and clinical features provide a better understanding of the factors that possibly are associated with the malignant transformation of OED. Furthermore, these results contribute to supporting a prompt and accurate recognition of these lesions in clinical practice.

Immunoexpression of cyclooxygenase-2 and p53 in oral squamous cell carcinoma

PURPOSE Cyclooxygenase-2 (COX-2) is an induced proinflammatory enzyme involved in various steps of carcinogenesis such as cell proliferation, reduction in apoptosis rates, and promotion of tumor angiogenesis. Mutation or inactivation of the tumor suppressor gene p53 is frequently observed in malignant neoplasms and is known to be involved in the early stages of carcinogenesis. Recent studies reveal a possible correlation between COX-2 and p53 expression in several malignant neoplasms. The present study analyzed the correlation between the expression of COX-2 and p53 in oral squamous cell carcinoma (OSCC) and evaluated the differences in the expression of these 2 proteins according to the histologic grade of malignancy of the tumor. MATERIALS AND METHODS Thirty-four cases of OSCC were graded according to the histologic grading system proposed by Bryne [Oral Dis 4(2) (1998) 70-77]. Immunoexpression of COX-2 and p53 was analyzed by counting 1000 neoplastic cells in 5 different fields at the deep invasive front of the tumor under a light microscope. On the basis of the number of immunopositive cells, the labeling index expressed as the percentage of positively stained cells was established for each marker. RESULTS Increased COX-2 expression in most specimens was observed, although no significant correlation was observed between COX-2 and p53 labeling indices (P > .05). Moreover, there were no significant differences in the expression of these proteins between high- and low-grade tumors (P > .05). CONCLUSION The increased expression of COX-2 in OSCC suggests a role for this protein in the pathogenesis and progression of oral cancer.

Analysis of local immunity in squamous cell carcinoma of the tongue and lower lip.

Antitumor immunity plays an important role in the development of and protection against malignancy. In general, patients with cancer are known to be immunologically compromised. The objective of this study was to evaluate local immunity in squamous cell carcinomas (SCCs) of the tongue and lower lip by immunohistochemistry, using anti-CD3, -CD4, -CD8, -CD25 and -zeta antibodies. Immunoexpression at the invasive front was compared considering anatomical tumor location and metastasis. The CD4/CD8 ratio was calculated for each case and associated with the variables. CD3+, CD4+, CD8+ and CD25+ cell counts were higher in SCCs of the lower lip and anti-zeta immunostaining was more evident in non-metastatic cases. CD8+ and CD25+ cell counts were also significantly correlated with tumor location (p=0.004 and p=0.004, respectively), with the observation of a larger number of these cells in SCCs of the lower lip. The CD4/CD8 ratio showed no significant association with metastasis or anatomical location. In conclusion, the clinical behavior of the oral SCC cases studied might be partially related to the immunohistochemical profile of the inflammatory infiltrate present at the invasive front.

Low miR-143/miR-145 Cluster Levels Induce Activin A Overexpression in Oral Squamous Cell Carcinomas, Which Contributes to Poor Prognosis.

Deregulated expression of activin A is reported in several tumors, but its biological functions in oral squamous cell carcinoma (OSCC) are unknown. Here, we investigate whether activin A can play a causal role in OSCCs. Activin A expression was assessed by qPCR and immunohistochemistry in OSCC tissues. Low activin A-expressing cells were treated with recombinant activin A and assessed for apoptosis, proliferation, adhesion, migration, invasion and epithelial-mesenchymal transition (EMT). Those phenotypes were also evaluated in high activin A-expressing cells treated with follistatin (an activin A antagonist) or stably expressing shRNA targeting activin A. Transfections of microRNA mimics were performed to determine whether the overexpression of activin A is regulated by miR-143/miR-145 cluster. Activin A was overexpressed in OSCCs in comparison with normal oral mucosa, and high activin A levels were significantly associated with lymph node metastasis, tumor differentiation and poor survival. High activin A levels promoted multiple properties associated with malignant transformation, including decreased apoptosis and increased proliferation, migration, invasion and EMT. Both miR-143 and miR-145 were markedly downregulated in OSCC cell lines and in clinical specimens, and inversely correlated to activin A levels. Forced expression of miR-143 and miR-145 in OSCC cells significantly decreased the expression of activin A. Overexpression of activin A in OSCCs, which is controlled by downregulation of miR-143/miR-145 cluster, regulates apoptosis, proliferation and invasiveness, and it is clinically correlated with lymph node metastasis and poor survival.

Changes in immunoexpression of E-cadherin and β-catenin in oral squamous cell carcinoma with and without nodal metastasis

The aim of this study is to analyze the immunohistochemical expression of E-cadherin and beta-catenin in oral squamous cell carcinoma to better understand the biological behavior of this lesion. The sample consisted of 15 cases of the tongue and 15 of the lower lip. The pattern and intensity of the labeling and the analysis of the percentage of tumor cells immunopositive in membrane for E-cadherin and beta-catenin were related to the anatomic location of the lesion, the presence or absence of nodal metastasis, and the histological gradation of malignancy in the tumor invasion front. The presence or absence of cytoplasmic and nuclear labeling was also recorded. The membrane expression for E-cadherin and beta-catenin predominately displayed a heterogeneous pattern in the carcinomas studied. No significant difference was observed between the expression pattern and the quantity of cells immunopositive for E-cadherin and beta-catenin and the anatomic location of the lesion or the presence or absence of nodal metastasis. However, a statistically significant difference was found between the reduced expressio\n of these proteins and the high malignancy score. The reduced immunoexpression of these proteins in the membrane may be related to the high degree of cell indifferentiation in cases of oral squamous cell carcinoma with high scores.

Sialolipoma of minor salivary glands

Sialolipoma is a recently described histologic variant of lipoma and is characterized by well-demarcated proliferation of mature adipocytes with secondary entrapment of salivary gland elements. These tumors have been observed in both the major and minor salivary glands, with more than 20 cases being reported in the English literature. In general, the clinical presentation of sialolipomas of the minor salivary glands suggests a diagnostic hypothesis of salivary gland lesions, commonly neoplasms. In the major salivary glands, the clinical features suggest either a salivary gland neoplasm or a lipoma. Surgical excision is the treatment of choice for sialolipomas, with no reports of recurrence or malignant transformation. The present article reports 4 additional cases of sialolipoma, all of them affecting the minor salivary glands, and reviews the literature regarding clinicopathologic aspects, differential diagnosis, and therapeutic management of this recently recognized histologic variant of lipoma.

Origin of stellate giant cells in oral fibrous lesions determined by immunohistochemical expression of vimentin, HHF-35, CD68 and factor XIIIa

Aims: To determine the origin of mono‐, bi‐ and multinucleate stellate giant cells in giant cell fibroma, fibrous hyperplasia and fibroepithelial polyp of the oral mucosa. Methods: Ten cases of each lesion were studied immunohistochemically using anti‐vimentin, ‐HHF‐35, ‐CD68 and ‐factor XIIIa antibodies. Immunoreactivity of the cells was determined in the papillary and reticular lamina propria of these lesions. Results: Vimentin positivity in both the papillary and reticular lamina propria was observed for most samples, especially giant cell fibroma cases. Conclusions: The immunohistochemical findings of the present study suggest that the mono‐, bi‐ or multinucleate stellate giant cells observed in the lesions studied derived from the fibroblastic lineage.

Actinic cheilitis: clinicopathologic profile and association with degree of dysplasia

Actinic cheilitis (AC) is a potentially malignant disorder of the lip caused by exposure to solar radiation.