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Oral squamous cell carcinoma is associated with decreased bcl-2/bax expression ratio and increased apoptosis

Expression of bcl-2 and bax and apoptosis were studied in fresh frozen samples of normal oral epithelium (OE, n = 7) and oral squamous cell carcinomas (OSCC, n = 16) by immunohistochemistry and the TUNEL method. In OE, bcl-2 was expressed in both basal (96.6% +/- 2.3% [mean +/- SD]) and suprabasal (91.8% +/- 6.2%) compartments. In OSCC, compared with OE, there was a marked reduction of bcl-2-positive cells in the basal part, and in the central parts of well-differentiated (33.0% +/- 19.7%, P < .001) and moderately differentiated (6.1% +/- 4.6%, P < .001) and also in poorly differentiated (1.9% +/- 0.2%, P < .001) tumors. More cells expressed bax in the suprabasal layer of OE (65.6% +/- 9.9%) and central parts of OSCC than in the basal layer of OE (19.1% +/- 4.1%) and basal parts of OSCC. A higher proportion of cells expressed bax in the central part of well-differentiated OSCC (74.3% +/- 8.2%) than in poorly differentiated OSCC (24.9% +/- 9.7%, P < .001). Apoptotic cell death was more pronounced in OSCC (1.5% +/- 0.9%) than in OE (0.4% +/- 0.1%, P < .05). We conclude that, in OSCC, compared with OE, there is a decreased bcl-2 expression, a lowered bcl-2/bax ratio and increased apoptosis. The expression of bax correlates with histological tumor grading in oral squamous cell carcinoma.

CD40, CD154, Bax and Bcl-2 Expression in Sjögren's Syndrome Salivary Glands: a Putative Anti-Apoptotic Role During its Effector Phases

Sjögrens syndrome (SS) is an autoimmune rheumatic disorder characterized by chronic lymphocytic infiltration and decreased secretion in the salivary glands (SGs). For some time, apoptosis has been suggested to constitute the major mechanism for acinar epithelial destruction during the effector phases; however, this is still controversial. We have recently demonstrated that despite the expression of Fas and FasL, the incidence of apoptosis is not increased in SS patients compared with control individuals. Our aim was therefore to further evaluate the expression of the pro‐ and anti‐apoptotic Bax and Bcl‐2 proteins. CD40 and CD154 expression was also investigated, as CD40 ligation has been suggested to protect cells from Fas‐mediated apoptosis. Immunohistochemical staining was performed on SG tissue from primary and secondary SS patients, a group of patients with non‐SS‐related degenerative changes as well as on healthy control individuals. The frequency of stained cells in the foci of infiltrating mononuclear cells (IMCs) and in the acinar and ductal epithelium was determined. We found the expression of Bcl‐2 but rarely Bax in SS SG IMCs. Bcl‐2 in epithelial cells was sparse, while Bax expression occurred frequently and with no significant difference between the patient groups. CD40 and CD154 expression was high among SS IMCs, while CD40 levels were slightly decreased in SS epithelium compared with controls. Elevated CD154 expression was found in SS epithelium, being significantly increased in the ducts. In conclusion, our study further supports the hypothesis about apoptosis resistance among SS focal IMCs and suggests a putative protective role of CD40 ligation in SS SG epithelium.

Decreased expression of bcl-2 in moderate and severe oral epithelia dysplasias

The bcl-2 gene family plays an important role in regulation of apoptosis. We previously reported loss of bcl-2 in peripheries of well and moderately differentiated oral squamous cell carcinoma tumour islands. We aimed to determine bcl-2 and bax gene expression in oral epithelial dysplasias (OED) in relation to apoptosis and proliferation. Samples of normal oral epithelium (OE, n=7), focal epithelial hyperplasia (n=9), mild (n=9), moderate (n=8) and severe (n=18) OED were evaluated by immunohistochemistry, the TUNEL method and in situ hybridisation for bcl-2 and bax mRNA. bcl-2 mRNA and protein were markedly decreased in the basal parts of moderate and severe OED compared with the basal layer of OE (P<0.001) and correlated with a 3-4 fold increase in apoptosis and increased proliferation. bax mRNA and protein were not significantly altered in normal, hyperplastic and dysplastic epithelia. From OE to severe OED, there was an inverse relationship between the bcl-2/bax ratio and apoptosis. Our results indicate that suppression of bcl-2 may have a role in oral tumourigenesis.

Loss of BCL-2 in the progression of oral cancer is not attributable to mutations

Background: BCL-2 and BAX are important in the regulation of apoptosis. There have been reports of loss of BCL-2 in basal cells of oral epithelial dysplasia (OED) and in oral squamous cell carcinoma (OSCC), and suppression of BAX in poorly differentiated OSCC. Aim: To investigate whether loss of BCL-2 in OED and OSCC, and of BAX in poorly differentiated OSCC could be attributed to BCL-2 and BAX mutations. Methods: Immunohistochemistry and in situ hybridisation were used to confirm BCL-2 and BAX expression. DNA was extracted from archival samples of OED (n  =  22) and OSCC (n  =  28). The connective tissue part from each section was collected separately and used as the normal reference. Results: No mutations were detected in BCL-2 or BAX that could explain their aberrant expression at the mRNA and protein levels in OED and OSCC. The reported A/G polymorphism at codon 7 of BCL-2 was detected in 18 of 50 samples and a novel C/T polymorphism at codon 100 was detected in three of 50 samples. Conclusions: No mutations were found that could explain loss of BCL-2 in oral dysplasia and carcinoma. An unreported C/T polymorphism in BCL-2 was detected. Downregulation of BCL-2 in OED and OSCC may be the result of transcriptional regulation.