Heterogeneity of PLAG1 gene rearrangements in pleomorphic adenoma
ABSTRACT Pleomorphic adenoma (PA), a benign mixed salivary gland tumor, has been associated with abnormal karyotypes in up to 70% of cases, with nonrandom involvement of 8q12, the locus of the pleomorphic adenoma (PLAG1) gene. In this study, cytogenetics and fluorescence in situ hybridization (FISH) were used to investigate PLAG1 involvement in PA from seven patients. There were two males and five females ranging in age from 25 to 65 years. Samples of parotid gland tissue from the tumor sites, set up as solid tumor cultures, showed a normal karyotype in two cases [46,XY;46,XX] and cytogenetic abnormalities in five cases (71%). The abnormalities comprised one variant translocation [t(1;4;8)(p32;q35;q12)], two classic translocations [t(5;8)(p13;q12)], one novel deletion [del(12)(p11.2p12.1)], and a novel insertion [ins(9;8)(p22;q12q21.1)]. FISH was performed in all cases by using two probes from the RP11 library, flanking PLAG1; a sequence 1.48 megabases (Mb) upstream and another 2.27 Mb downstream, covering a total area of 3.8 Mb. The PLAG1 gene was intact and normally situated in four cases - the 46,XY, 46,XX, del(12p), and one t(5;8). PLAG1 was disrupted in three cases - one t(5;8), ins(9;8), and t(1;4;8). In addition, genomic instability was seen in two cases, one with PLAG1 amplification in the form of a homogeneously staining region, and the other in der(8) ring formation. The data provide further unique cases showing the complexity of PLAG1 gene rearrangements in PA.
Value in Health 11/2005; 8(6). DOI:10.1016/S1098-3015(10)67566-3 · 2.89 Impact Factor
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ABSTRACT: Pleomorphic adenoma (PA) is the most common, benign tumor of the major salivary glands. Surgical resection is the treatment of choice. Initial preoperative workup of major salivary gland neoplasms often includes fine needle aspiration biopsy (FNAB) and magnetic resonance imaging (MRI) of the head and neck. Our objective was to assess the positive predictive value of FNAB and MRI in the evaluation of PA arising from within the major salivary glands. Retrospective chart review. All patients with a FNAB diagnosis of PA of the major salivary glands and who underwent surgical excision at our institution from 2001 to 2011 were identified. FNAB slides from these cases were reviewed by a cytopathologist for findings suggestive of PA: fibrillary stroma, mesenchymal elements, plasmacytoid myoepithelial cells, epithelial cells forming ducts or tubules, and the absence of nuclear atypia. For those patients with a preoperative MRI, the MRI studies were reviewed by a neuroradiologist for findings suggestive of PA, including homogenous T2 hyperintensity, well-circumscribed borders, and solid contrast enhancement. Positive predictive value (PPV) of these specific FNAB and MRI findings were calculated using chi-squared testing. One hundred forty-six patients met inclusion criteria, and 68 had preoperative MRI. PPV of a FNAB diagnosis of PA was 97.8%. Characteristic features of PA on FNAB (fibrillary stroma, mesenchymal elements, plasmacytoid myoepithelial cells, epithelial cells forming ducts or tubules, and the absence of nuclear atypia) and MRI (homogenous T2 hyperintensity, well-circumscribed borders, and solid contrast enhancement) all demonstrated PPVs of 95% or greater in patients with FNA diagnosis of PA. PPV of a FNAB diagnosis of PA in the major salivary glands is high. Among patients with a FNAB diagnosis of PA, specific MRI characteristics also have a high PPV. The diagnostic accuracy of these studies in combination allows for the confident preoperative diagnosis of PA. 4. Laryngoscope, 2013.The Laryngoscope 12/2013; 123(12). DOI:10.1002/lary.24247 · 2.03 Impact Factor
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ABSTRACT: The aim of this study was to investigate the neoplastic potential of the PA of minor oral salivary glands measured by apoptosis (Bcl-2, Bax and p53), mucosecretory activity (MUC1), and cellular proliferation (Ki-67). Thirty-one cases of PA of the oral cavity and four controls (C) taken from normal oral minor salivary glands were analyzed using the immunohistochemistry technique. The proteins were detected utilizing a semi-quantitative method (scores) as follows: (-) negative ≤5%, (+) low 6-25%, (++) moderate 26-50% and (+++) high >50% of positive tumour cells. The apoptotic indices were evaluated by the ratio Bcl-2/Bax. Non-parametric comparison and correlation tests were used for analysis. The data showed high staining of anti-apoptotic protein Bcl-2 in both groups (PA=57.9%; C=67.7%) and a significantly lower expression of pro-apoptotic protein Bax (PA=22.7%; C=97.7%) and MUC1 (PA=14%; C=82.3%) in PA than in C (p<0.001). On the other hand, a similar expression of Ki-67 and p53 proteins (≤5%) was seen in both PA and C. In PA, only 2/31 cases showed the ratio Bcl-2/Bax<1.There was no difference in cellular expression with regard to clinical variables or clinical outcome (p>0.05). The neoplastic potential of PA could be associated with an imbalance in apoptotic processes and a lower index of cellular proliferation. Mucosecretory activity does not play a significant role in primary PA.Archives of oral biology 03/2014; 59(6):578-585. DOI:10.1016/j.archoralbio.2014.03.002 · 1.88 Impact Factor