BACKGROUND Tumor budding is a readily detectable histopathological feature and has been recognized as an adverse prognostic factor in several human cancers. However, the prognostic value of tumor budding in tongue squamous cell carcinoma (TSCC) has not been reported. The purpose of this study is to assess the correlation of tumor budding with the clinicopathologic features, and the known molecular biomarkers (E-cadherin and Vimentin), as well as to evaluate its prognostic significance for TSCC. METHODS Archival clinical samples of 230 patients with TSCC were examined for tumor budding. Immunohistochemistry analyses were performed to examine the expression of E-cadherin and Vimentin. Statistical analyses were carried out to assess the correlation of tumor budding with clinicopathologic parameters and patient survival. The potential association between tumor budding and alterations of E-cadherin and Vimentin expression was also assessed. RESULTS Of the 230 TSCC cases examined, tumor budding was observed in 165 cases (71.7%), with a mean tumor bud count of 7.5 (range from 1 to 48 buds). High-intensity budding (≥ 5 tumor buds) was observed in 111 cases (48.3%). Statistical analysis revealed that tumor budding was associated with tumor size (P<0.05), differentiation (P<0.05), clinical stage (P<0.05), lymph node metastasis (P<0.01), and correlated with reduced overall survival. In addition, significant associations were observed among tumor budding and the deregulation of E-cadherin (P<0.001) and Vimentin (P<0.001). CONCLUSIONS Tumor budding, which associates with epithelial-mesenchymal transition, is a frequent event and appears to be an independent prognostic factor in TSCC.

White matter hyperintensities (WMHs) are a frequent finding on T2-weighted MRI of the brain in elderly individuals, but their prevalence and severity in younger asymptomatic populations is less well studied. We report the topography of WMHs on T2-weighted fluid inversion recovery (FLAIR) MRI in 428 individuals aged 44-48 years recruited randomly from a healthy community sample. WMHs were delineated from FLAIR and T1-weighted scans by using a computer algorithm, further verified and then classified using k-nearest neighbor (kNN) algorithm into deep WMH (DWMH), and periventricular WMH (PVWMH), which included extended periventricular "rims" and frontal and occipital "caps". Small caps and pencil-thin rims were not taken as WMHs for this analysis. The new computer algorithm was validated and compared with the scores of visual rating, and the correspondence between the two methods was high. We found that 218 (50.9%) subjects had WMHs. 146 of the 218 (34.1% of whole sample population of 428) subjects had deep white matter hyperintensities (DWMHs). The average number of WMH clusters (occurrences) per brain was 1.37 (0.94 for DWMH and 0.43 for pathological PVWMH) and the mean WMH tissue volume was 0.278 ml. There was no significant sex difference in the severity and distribution of WMHs. The study suggests that small punctate or focal WMHs are common in the brains of individuals in their 40s, and may represent an early stage of development of these lesions.

Background Tumor budding is a valuable prognostic marker in oral tongue squamous cell carcinoma (OTSCC) but lacks a standardized scoring system. The aim of this study was to evaluate the prognostic value of tumor budding for OTSCC patients based on the scoring system recommended by the International Tumor Budding Consensus Conference (ITBCC) 2016. Methods Tumor budding was scored as ITBCC recommended in 255 patients with OTSCC. Then, associations between tumor budding and clinicopathologic parameters were examined. Among them, 136 patients with follow‐up data available were used to evaluate overall survival (OS) by the Kaplan‐Meier method. Prognostic value of tumor budding was assessed by Cox regression analysis. The inter‐observer and intra‐observer agreement was calculated by the kappa statistic. Results Tumor budding score was associated with lymph node metastasis, differentiation, invasive pattern, lymphoid infiltrate, tumor relapse, invasive depth, and reduced OS in OTSCC patients. The Cox analysis showed high budding score was an independent prognostic factor in patients with all clinical stage and patients with clinical early‐stage OTSCC. The high kappa values were achieved in intra‐observer and inter‐observer. Conclusions International Tumor Budding Consensus Conference scoring system is a simple, reliable, and reproducible method to measure tumor budding in OTSCC, which should be included in the routine pathological report.

New imaging techniques present an opportunity to examine white matter pathology in great detail in younger populations. Standardized methods to examine such pathology and its determinants will help inform strategies for their prevention, which is an important component of a healthy ageing agenda.

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Abnormal expression of β-catenin contributes to tumor development, progression, and metastasis in various cancers. However, little is known about the relationship between abnormal expression of β-catenin and cisplatin chemotherapy in oral squamous cell carcinoma (OSCC). The present study aimed to investigate the effect of β-catenin on OSCC cisplatin resistance and evaluated the drug susceptibility of stable cell lines with β-catenin knockin and knockdown. In this study, we found that higher expression level of β-catenin can be observed in CDDP-treated cell lines as compared with the control group. Furthermore, the expression levels of β-catenin increased in both a concentration- and time-dependent manner with the cisplatin treatment. More importantly, the nuclear translocation of β-catenin could also be observed by confocal microscope analysis. Stable cell lines with CTNNB1 knockin and knockdown were established to further investigate the potential role and mechanism of β-catenin in the chemoresistance of OSCC in vitro and in vivo. Our findings indicated that overexpression of β-catenin promoted cisplatin resistance in OSCC in vitro and in vivo. We confirmed that GSK-3β, C-myc, Bcl-2, P-gp, and MRP-1 were involved in β-catenin-mediated drug resistance. Our findings indicate that the Wnt/β-catenin signaling pathway may play important roles in cisplatin resistance in OSCC.

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