ARID4B is a good biomarker to predict tumour behaviour and decide WHO grades in gliomas and meningiomas

AimsAlthough ARID4B is known to promote tumour metastasis in breast cancer and inhibit transformation and progression in leukaemia, the possible effect of ARID4B on primary brain tumours (PBTs) is not well characterised. We tested the hypothesis that expression of ARID4B correlates with WHO grade and survival in patients with PBTs.MethodsWestern blot analysis was performed on protein lysates prepared from normal brain tissue and glioma cell lines (U87MG, LN229, GBM8401 and U118MG). Subsequently, immunohistochemical analysis of ARID4B was performed on 2 tissue microarrays, including 12 normal brain tissues, 63 meningiomas with different subtypes, 232 gliomas of various grades and degrees of differentiation, 8 central neurocytomas and 4 chordomas. The ARID4B immunostaining score was calculated by multiplying the intensity score by the percentage of tumour cells expressing ARID4B.ResultsIn vitro, ARID4B protein expression was increased in some glioma cell lines. In addition, the average ARID4B immunostaining score was 38.03, 79.09, 129.76 and 119.32, respectively, in gliomas of WHO grade I, II, III and IV. Higher ARID4B immunostaining score was significantly correlated with more advanced WHO grade of gliomas (p=7.4×10–6) and meningiomas. Finally, higher ARID4B expression tended to the shorter survival rates, but did not reach statistical significance.ConclusionsARID4B overexpression presented in most of PBTs, rather than non-neoplastic brain tissue, and correlated with WHO grades in meningiomas and gliomas. Therefore, ARID4B is a satisfactory biomarker to highlight tumour component and predict tumour behaviour in primary brain neoplasms.

Upregulation of human β-defensin-3 and cathelicidin LL-37 in Kaposi’s sarcoma

Background: Kaposi’s sarcoma (KS) is a rare neoplasm of lymphatic endothelial cells. Human herpes virus 8 (HHV-8) is considered to be a necessary, but not sufficient causal agent of KS and additional cofactors remain unknown. In this study we evaluated the expression of human β defensin (HBD)-3 and LL-37 in cutaneous lesions of KS in comparison to the healthy skin of normal subjects.Methods: We performed a quantitative immunohistochemical study of HBD-3 and LL-37 on skin lesions from 18 patients having KS, and on healthy skin from 12 normal controls.Results: HBD-3 and LL-37 were significantly upregulated in epidermal and dermal specimens of all KS patients in comparison to normal skin of healthy controls. The immunostaining score of dermal HBD-3 was significantly higher in nodular lesions (9.6 ± 2.4) versus plaque lesions (4.1 ± 2.2), P = 0.001. Also the immunostaining score of dermal LL-37 was significantly higher in nodular lesions versus plaque lesions (P = 0.001).Conclusions: We have demonstrated for the first time that HBD-3 and LL-37 are significantly upregulated in lesional skin of KS in comparison to the skin of healthy controls. The obtained data suggest a possible involvement of these antimicrobial peptides in the pathogenesis of KS. However, the biological significance of HBD-3 and LL-37 in KS lesions needs further research.

Expression of Survivin and Cortactin in Colorectal Adenocarcinoma: Association with Clinicopathological Parameters

Objective: Survivin and cortactin are factors that promote tumor progression. We tested the hypothesis that survivin and cortactin expressions correlate with the clinico-pathological parameters of colorectal adenocarcinomas and survival time. Methods: Immunohistochemical analysis of survivin and cortactin were performed using tissue microarrays of 119 specimens from 18 well, 50 moderately, and 27 poorly differentiated colorectal adenocarcinomas and 24 colorectal adenomas with dysplasia. As control, 10 specimens of normal colorectal epithelia were included.Results: The percentage of cells immunostained and the immunostaining scores for survivin and cortactin were all significantly higher in well-, moderately, and poorly differentiated colorectal adenocarcinomas than in normal colorectal epithelia. The survivin immunostaining score was significantly correlated with T, M, and AJCC/TNM stages (p `0.05). For cortactin, the score was significantly correlated with T and M stages (p ` 0.05). Higher survivin immunostaining score was associated with higher mortality.Conclusions: Higher expression of survivin and cortactin correlates significantly with tumor stages and shorter survival time. Survivin and cortactin may be good biomarkers of aggressiveness of colorectal adenocarcinomas. Our findings require validation in independent cohorts and these data support the potential targeting of survivin and cortactin for the development of novel therapeutic strategies.

Vascular endothelial growth factor gene and protein: strong expression in thyroiditis and thyroid carcinoma

Angiogenesis is implicated in several pathological conditions, such as inflammation and tumor growth. Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is a potent stimulator of endothelial cell proliferation in vitro and in vivo. The present work aimed to compare VEGF expression in human normal thyroid glands, thyroiditis tissue and thyroid carcinomas using immunohistochemistry and in situ hybridization (ISH). Both chronic lymphocytic thyroiditis and differentiated thyroid carcinomas were found to strongly express VEGF mRNA and encode larger amounts of VEGF than normal thyroid tissue as attested by a VEGF immunostaining score. In addition, tumor samples from patients with metastases showed a higher immunostaining score than their non-metastatic counterparts (P<0.05). Carcinomas with the greatest contents of VEGF mRNA and VEGF protein had the most intense mitogenic activity. Special focus on endothelial cells showed intense mitogenic activity in neoplastic tissues in contrast to the total quiescence of endothelial cells in non-tumoral tissues. An intense VEGF production by differentiated thyroid carcinoma, attested either by a higher immunostaining score or a strong VEGF mRNA expression using ISH, could be a promising marker of tumor aggressiveness and may also be useful as a predictor of metastatic potential.