Microvascular density and tumor budding in oral squamous cell carcinoma

Background: Oral squamous cell carcinoma (OSCC) is the most prevalent malignant head and neck tumor, excluding the nonmelanoma skin cancer. Despite recent advances in the diagnosis and treatment, the disease's mortality rate is nonetheless high. The presence of isolated neoplastic cells or small clusters of up to four cells at the tumor's invasive front, named tumor budding, is associated with a worse prognosis in OSCC. Angiogenesis has also been recognized as a determining factor in the progression of malignancies and in the development of metastases. Several studies have investigated the assessment of microvascular density (MVD) as a potential prognostic factor in OSCC. This study aimed to evaluate, in OSCC, differences in MVD between tumors with high-intensity tumor budding and tumors with low-intensity or no tumor budding. In samples with high-intensity tumor budding, differences in MVD between the budding area and the area outside the budding were also evaluated. Moreover, the study assessed differences in MVD concerning clinicopathological characteristics such as sex, age, tobacco smoking, tumor location and tumor size. Material and methods: One hundred and fifty [150] samples of OSCC were subjected to immunohistochemistry to assess the intensity of tumor budding (by immunostaining for multi-cytokeratin) and MVD (by immunostaining for CD34 and CD105, independently). The data were treated using descriptive and analytical statistics. (AU)

Lymphatic Vascular Density, the Expression of Podoplanin and Tumor Budding in Oral Squamous Cell Carcinoma.

BACKGROUND: Notwithstanding recent advances in oral squamous cell carcinoma (OSCC) management, its mortality rate is still high. It is imperative to investigate new parameters that are complementary to clinical staging for OSCC to provide better prognostic insight. The presence of isolated neoplastic cells or small clusters of up to four cells at the tumor's invasive front, called tumor budding, is a morphological marker of OSCC with prognostic value. Increased lymphatic vascular density (LVD) and a high expression of podoplanin in neoplastic cells have also been associated with worse prognosis in OSCC. To investigate these markers in OSCC, we evaluated differences in LVD and the expression of podoplanin in neoplastic cells between tumors with high-intensity tumor budding versus low-intensity or no tumor budding. In the samples of high-intensity budding, differences in those parameters between the​​ budding area and the area outside the budding were also evaluated. Furthermore, the study assessed differences in LVD and in the expression of podoplanin in neoplastic cells concerning OSCC clinicopathological characteristics. METHODS: To those ends, we subjected 150 samples of OSCC to immunohistochemistry to evaluate the intensity of tumor budding (via multi-cytokeratin immunostaining). Moreover, the 150 samples of OSCC and 15 specimens of normal oral mucosa (used as a control) were employed to assess LVD and the expression of podoplanin (in neoplastic cells of OSCC and in the lining epithelium of normal oral mucosa), both via podoplanin immunostaining. Data were processed into descriptive and analytical statistics. RESULTS: No differences were observed neither in the LVD nor in the expression of podoplanin in neoplastic cells concerning sex, age, tobacco smoking, tumor location and tumor size. The LVD was greater in OSCC and in tumors with high-intensity budding than in normal mucosa but did not differ between normal mucosa and tumors with low-intensity or no tumor budding. The data analyses also revealed that LVD was greater in tumors with high-intensity tumor budding than in tumors with low-intensity or no budding and showed no difference in LVD between the budding area and the area outside the budding. When compared to the lining epithelium of the normal mucosa, the expression of podoplanin was greater in neoplastic cells of OSCC, tumors with high-intensity budding and tumors with low-intensity or no tumor budding. The expression of podoplanin in neoplastic cells was also greater in tumors with high-intensity budding and, within those tumors, greater in the budding area than in the area outside de budding. CONCLUSION: Those findings support the hypothesis that tumor budding is a biological phenomenon associated with the progression and biological behavior of OSCC.