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.

The role of intratumoral lymphovascular density in distinguishing primary from secondary mucinous ovarian tumors

OBJECTIVE: Ovarian mucinous metastases commonly present as the first sign of the disease and are capable of simulating primary tumors. Our aim was to investigate the role of intratumoral lymphatic vascular density together with other surgical-pathological features in distinguishing primary from secondary mucinous ovarian tumors. METHODS: A total of 124 cases of mucinous tumors in the ovary (63 primary and 61 metastatic) were compared according to their clinicopathological features and immunohistochemical profiles. The intratumoral lymphatic vascular density was quantified by counting the number of vessels stained by the D2-40 antibody. RESULTS: Metastases occurred in older patients and were associated with a higher proportion of tumors smaller than 10.0 cm; bilaterality; extensive necrosis; extraovarian extension; increased expression of cytokeratin 20, CDX2, CA19.9 and MUC2; and decreased expression of cytokeratin 7, CA125 and MUC5AC. The lymphatic vascular density was increased among primary tumors. However, after multivariate analysis, the best predictors of a secondary tumor were a size of 10.0 cm or less, bilaterality and cytokeratin 7 negativity. Lack of MUC2 expression was an important factor excluding metastasis. CONCLUSIONS: The higher intratumoral lymphatic vascular density in primary tumors when compared with secondary lesions suggests differences in the microenvironment. However, considering the differential diagnosis, the best discriminator of a secondary tumor is the combination of tumor size, laterality and the pattern of expression of cytokeratin 7 and MUC2. .