Exploring the combination of tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding with WHO histopathological grading on early-stage oral squamous cell carcinoma prognosis.

BACKGROUND: While the relevance of the World Health Organization histopathological grading system as a prognostic tool for oral squamous cell carcinoma has received many critics, other histopathological features such as tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding are displaying promising results. Here, we evaluated the prognostic impact of the incorporation of tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding into World Health Organization histopathological grading for patients with oral squamous cell carcinoma. METHODS: A total of 95 patients with early-stage oral squamous cell carcinoma were enrolled in the study, and World Health Organization tumor grading, tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding were evaluated in surgical slides stained with hematoxylin and eosin. Survival analyses for cancer-specific survival and disease-free survival were performed using Cox regression models, and receiver operating characteristic curves were applied for assessment of the performance of the combinations. RESULTS: Tumor-stroma ratio (stroma-rich) was significantly and independently associated with both shortened cancer-specific survival and poor disease-free survival, individually and in combination with World Health Organization histopathological grading. The combination of tumor-stroma ratio with World Health Organization grading did not improve the discriminatory ability compared to tumor-stroma ratio alone. Although low tumor-infiltrating lymphocytes were associated with shortened cancer-specific survival, the association did not withstand multivariate analysis. However, in combination with World Health Organization grading, low tumor-infiltrating lymphocytes were independently associated with poor cancer-specific survival. The combination of tumor-infiltrating lymphocytes and World Health Organization histopathological grading displayed a better discrimination of poor cancer-specific survival than tumor-infiltrating lymphocytes alone, but not at a significant level. CONCLUSION: Our findings support tumor-stroma ratio as a potential prognostic marker for patients with oral squamous cell carcinoma, and the incorporation of tumor-infiltrating lymphocytes into the World Health Organization grading system improves the prognostic ability of the tumor grading alone.

Impact of Bifidobacterium animalis subsp. lactis HN019 probiotic in the prevention of periodontitis associated with immunosuppression.

BACKGROUND: This study evaluated the effects of the probiotic Bifidobacterium animalis subsp. lactis HN019 (HN019) in the development of experimental periodontitis (EP) in rats submitted to chemotherapy (5-fluorouracil [5FU]). METHODS: Eighty male rats were divided into the following groups: control (C); treated with 5FU (60 mg/kg at day 30 and 40 mg/kg at day 32); treated with probiotic (HN019) (daily, for 44 days, starting at day 0); treatment with 5FU and probiotic (5FU-HN019); only EP (EP) (ligature placed on lower first molars at day 30, maintained for 14 days); EP and treatment with 5FU (EP-5FU); EP and treatment with probiotic (EP-HN019); and EP and treatment with 5FU and probiotic (EP-5FU-HN019). Euthanasia occurred at day 44. Morphometric, histomorphometric, microtomographic, immunohistochemical, immunoenzymatic, and gene expressions analyses were performed. The data obtained were statistically analyzed (p < 0.05). RESULTS: The EP-5FU-HN019 group showed less bone and connective tissue loss when compared with EP-5FU group, while EP-HN019 and EP-5FU-HN019 groups had greater bone volume than EP and EP-5FU groups, respectively (p < 0.05). A decrease in immunostaining for tartrate-resistant acid phosphatase and RANKL, an increase for osteoprotegerin and lower interleukin-1ß levels were observed in EP-5FU-HN019 group, when compared with EP-5FU group (p < 0.0001). Probiotic therapy led to an increase in the proportions of B. lactis in the feces (p = 0.0018), but not in the biofilm, and reduced the expression of Fusobacterium nucleatum and Prevotella intermedia in the biofilm (p < 0.0001). CONCLUSION: B. lactis HN019 reduced the severity of EP in rats submitted to chemotherapy, modulating immunoinflammatory parameters in periodontal tissues and reducing periodontopathogens expression on biofilm in rats submitted to chemotherapy.