Aberrant Protein Expression and Promoter Methylation of p16 Gene Are Correlated With Malignant Transformation of Salivary Pleomorphic Adenoma

2011 ◽  
Vol 135 (7) ◽  
pp. 882-889
Author(s):  
Yu-Hua Hu ◽  
Chun-Ye Zhang ◽  
Zhen Tian ◽  
Li-Zhen Wang ◽  
Jiang Li
Keyword(s):  
Protein Expression ◽  
Pleomorphic Adenoma ◽  
Malignant Transformation ◽  
Promoter Methylation ◽  
Intracellular Localization ◽  
Carcinoma Ex Pleomorphic Adenoma ◽  
P16 Gene ◽  
P16 Protein ◽  
Polymerase Chain ◽  
Lower Expression

Abstract Context.—The significance of promoter methylation of the p16 gene and intracellular localization of p16 protein in the carcinogenesis of salivary carcinoma ex pleomorphic adenoma (Ca-ex-PA) is not clear. The correlation of the promoter methylation of the p16 gene and the expression and localization of p16 protein in Ca-ex-PA need to be further clarified. Objective.—To investigate the p16 protein expression and promoter methylation of p16 gene in Ca-ex-PA and their roles in the malignant transformation of pleomorphic adenoma to Ca-ex-PA. Design.—The p16 protein expression and promoter methylation of the p16 gene were determined in both benign and malignant components of 50 primary salivary Ca-ex-PA tissues by immunohistochemistry and methylation-specific polymerase chain reaction. Expression of p16 protein and promoter methylation of the p16 gene between the benign and the malignant components was compared statistically. Results.—The tumor cells in the malignant components showed significantly higher p16 protein expression in the cytoplasm and lower expression in the nuclei than those in the benign components. Promoter methylation frequency of the p16 gene in the malignant components (36%) was significantly higher than that in the benign components (16%). There were no correlations between p16 protein expression and promoter methylation of the p16 gene in either benign or malignant components. Conclusions.—Overexpression of p16 protein in the cytoplasm and decreased expression of p16 protein in the nucleus may play important roles in the evolution of pleomorphic adenoma to Ca-ex-PA. Promoter methylation of the p16 gene may be correlated with the malignant transformation of pleomorphic adenoma.

Analysis of Amplified Genes in Samples of Pleomorphic Adenoma and Carcinoma Ex Pleomorphic Adenoma by CGH-Array Technique

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S51-S51
Author(s):  
Erika Egal ◽  
Welligton Sabino ◽  
João Scarini ◽  
Reydson Souza ◽  
Albina Altemani ◽  
...  
Keyword(s):  
Pleomorphic Adenoma ◽  
Malignant Transformation ◽  
Genetic Disorders ◽  
Benign Lesion ◽  
Carcinoma Ex Pleomorphic Adenoma ◽  
Low Grade ◽  
Cgh Array ◽  
Microsoft Excel ◽  
Histopathological Subtype ◽  
Common Target

Abstract Introduction Pleomorphic adenoma (PA) is a benign lesion of the salivary glands that can suffer malignant transformation to carcinoma ex adenoma pleomorphic (CXPA). The pathogenesis of CXPA has been attributed to the accumulation of genetic disorders in preexisting PAs. However, there is no confirmation whether there is a common target gene involved in all histopathological subtypes or the decisive factors for malignant transformation in a histopathological subtype are specific. Objectives To further analyze genes found in PA and CXPA using the CGH-array technique. The genes found were analyzed using the InteractiVenn virtual tool (http://www.interactivenn.net/) and grouped into a Microsoft Excel worksheet. Results: Of the 460 genes amplified in the studied samples, 287 (62.4%) were related only to CXPA, whereas 144 (31.3%) were related to residual PA. Twenty-nine (6.3%) of these genes were common between residual PA and CXPA. Regarding the degree of invasion of CXPA, there was an increase in the number of genes amplified as the degree of invasion and aggression increased: 8 genes related to intracapsular CXPA, 65 to minimally invasive CXPA, and 373 to weakly invasive. Moreover, when comparing residual AP and intracapsular CXPA, two genes were common to these groups: ERRB2 and GRB7. As for the histological subtype, the high-grade samples had more amplifications (320 amplified genes) than the low-grade ones (129 genes). Three of these genes were common among residual PAs and CXPA: HMGA2, RPSAP52, and LOC100129940. As for the replicates, MYNC, ERBB2, BRIP1, and HMGA2 were the most repeated amplified genes in the residual PAs. HMGA2, ERRBB2, CDK12, RPSAP52, LOC100129940, and LOC100507250 were the genes with the most replicates in CXPA. Conclusion HMGA2, ERRB2, and RPSAP52 may play a key role in PA carcinogenesis, whereas GRB7, CDK12, MYNC, and BRIP1 appear to act as coadjutants.

Loss of expression of Plag1 in malignant transformation from pleomorphic adenoma to carcinoma ex pleomorphic adenoma

2016 ◽  
Vol 57 ◽  
pp. 152-159 ◽  
Author(s):  
Beatriz Samara de Brito ◽  
Natália Giovanelli ◽  
Erika Said Egal ◽  
Celeste Sánchez-Romero ◽  
Juliana de Souza do Nascimento ◽  
...  
Keyword(s):  
Pleomorphic Adenoma ◽  
Malignant Transformation ◽  
Carcinoma Ex Pleomorphic Adenoma

scholarly journals Quantitative promoter methylation differentiates carcinoma ex pleomorphic adenoma from pleomorphic salivary adenoma

2010 ◽  
Vol 103 (12) ◽  
pp. 1846-1851 ◽  
Author(s):  
A G Schache ◽  
G Hall ◽  
J A Woolgar ◽  
G Nikolaidis ◽  
A Triantafyllou ◽  
...  
Keyword(s):  
Pleomorphic Adenoma ◽  
Promoter Methylation ◽  
Carcinoma Ex Pleomorphic Adenoma

Malignant transformation of the salivary gland pleomorphic adenoma in myoepithelial carcinoma – the report of two cases

2019 ◽  
Vol 8 (1) ◽  
pp. 52-55
Author(s):  
Paulina Szabelska ◽  
Anna Rzepakowska ◽  
Benedykt Szczepankiewicz ◽  
Elżbieta Niemczyk ◽  
Ewa Osuch-Wójcikiewicz ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Surgical Treatment ◽  
Salivary Glands ◽  
Pleomorphic Adenoma ◽  
Malignant Transformation ◽  
Benign Tumor ◽  
Complete Recovery ◽  
Surrounding Tissue ◽  
Carcinoma Ex Pleomorphic Adenoma ◽  
Myoepithelial Carcinoma

A multiform adenoma is the most commonly diagnosed benign tumor of the salivary glands. In the majority of patients, surgical resection of the tumor with the adequate surrounding tissue of salivary gland allows for complete recovery. A small percentage of the cases is a recurring pleomorphic adenoma. Even more rarely the diagnosis of carcinoma ex pleomorphic adenoma is made. The study presents two clinical cases of the malignant transformation of pleomorphic adenoma into the myoepithelial carcinoma. The surgical treatment and additional radiotherapy were performed in both cases.

scholarly journals Carcinoma ex Pleomorphic Adenoma in the Parapharyngeal Space

2013 ◽  
Vol 28 (1) ◽  
pp. 24-27
Author(s):  
Sudipta Pal ◽  
Sampurna Pati ◽  
Somnath Saha ◽  
Vedula Padmini Saha
Keyword(s):  
Salivary Gland ◽  
Pleomorphic Adenoma ◽  
Malignant Transformation ◽  
Parapharyngeal Space ◽  
Minor Salivary Gland ◽  
Salivary Gland Tumor ◽  
Carcinoma Ex Pleomorphic Adenoma ◽  
Gland Tumor ◽  
Mandibular Swing ◽  
Operative Recovery

Objective: To present a case of carcinoma ex pleomorphic adenoma in the parapharyngeal space and discuss its management.   Methods: Design:            Case Report Setting:           Tertiary Government Teaching Hospital Subjects:         One   Results:  A 40-year-old male patient with dysphagia for three months and a left-sided mucosa-covered oropharyngeal mass was found to have a prestyloid parapharyngeal lesion on CT Scans. Fine Needle Aspiration Cytology (FNAC) revealed a pleomorphic adenoma. With a past history of parapharyngeal pleomorphic adenoma excised transorally three years before, the present mass was excised by mandibular swing approach. Post-operative recovery was uneventful, but the final histopathological report was carcinoma ex pleomorphic adenoma.   Conclusion: Malignant transformation should be suspected in recurrent salivary tumors in the parapharyngeal space. Provided there was truly no pre-existing malignant focus in the originally-excised tumor, and that early recurrence was not due to inadequate initial excision, this patient had a rare condition where the same tumor underwent malignant transformation within 3 years only. To the best of our knowledge, such an early transformation to malignancy of a minor salivary gland tumor of the parapharyngeal space has not been reported in the English literature.   Keywords: carcinoma ex pleomorphic adenoma, pleomorphic adenoma, carcinoma,  parapharyngeal space, malignant, transformation, minor salivary gland tumor,  mandibular swing

Analysis of the Expression of Genes Related to Lipidic and Glycogenic Metabolism in Pleomorphic Adenomas and Carcinomas Ex Pleomorphic Adenomas

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S135-S136
Author(s):  
Erika Egal ◽  
Joao Scarini ◽  
Larissa Fernandes ◽  
Welligton Sabino ◽  
Reydson Souza ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Pleomorphic Adenoma ◽  
Malignant Transformation ◽  
Fatty Acid Synthase ◽  
Carcinoma Ex Pleomorphic Adenoma ◽  
Glut 1 ◽  
Significant Difference ◽  
Pleomorphic Adenomas

Abstract Introduction The carcinoma ex pleomorphic adenoma (CXPA) arises from a pleomorphic adenoma (PA) and is supposed to gain lipogenesis and glycogenesis during its malignant transformation. Increased lipogenesis is a characteristic of cancer cells, consisting of increased fatty acid synthesis by the enzyme fatty acid synthase (FASN) and by the accumulation of cytoplasmic lipid droplets, which express adipophilin. The increase in glycolytic metabolism has been associated with the activity of glycolytic enzymes and glucose transporters (GLUTs), whose expression is induced by HIF-1 (inducing factor of hypoxia 1). Objectives To analyze the gene expression of FASN, adipophilin, HIF-1α, and GLUT-1 in PA and CXPA samples. Methodology Gene expression analysis of the FASN, adipophilin, HIF1-α, and GLUT-1 genes was performed by the real-time PCR (qPCR) method. Fourteen cases of PA and 14 cases of CXAP were evaluated. Results FASN, adipophilin, HIF-1α, and GLUT-1 were more expressed in CXAP than in AP, although there was no significant difference between levels of adipophilin expression in CXPA and PA. Conclusion Increased expression of FASN, HIF1-α, and GLUT-1 in CXAP may be associated with malignant transformation of PA, while additional studies are needed to understand the role of adipophilin in PA carcinogenesis. Moreover, this is the first study to investigate the role of these genes in the malignant transformation of PA.

scholarly journals Expression of p16Ink4a protein in pleomorphic adenoma and carcinoma ex pleomorphic adenoma proves diversity of tumour biology and predicts clinical course

2021 ◽  
pp. jclinpath-2021-207440
Author(s):  
Ewelina Bartkowiak ◽  
Krzysztof Piwowarczyk ◽  
Magdalena Bodnar ◽  
Paweł Kosikowski ◽  
Jadzia Chou ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Pleomorphic Adenoma ◽  
Malignant Transformation ◽  
Normal Tissue ◽  
Slow Growth ◽  
Clinical Course ◽  
Carcinoma Ex Pleomorphic Adenoma ◽  
Significant Difference ◽  
Normal Salivary Gland ◽  
Worse Prognosis

AimsThe aim of the study is to correlate p16Ink4a expression with the clinical courses of pleomorphic adenoma (PA), its malignant transformation (CaexPA) and treatment outcomes.MethodsRetrospective analysis (1998–2019) of 47 CaexPA, 148 PA and 22 normal salivary gland samples was performed. PAs were divided into two subsets: clinically ‘slow’ tumours characterised by stable size or slow growth; and ‘fast’ tumours with rapid growth rate.ResultsPositive p16Ink4a expression was found in 68 PA and 23 CaexPA, and borderline expression in 80 and 20, respectively. All 22 (100%) normal salivary gland samples presented with no p16Ink4a expression. Significant difference in p16Ink4a expression was observed between normal tissue, PA and CaexPA (χ2 (4)=172,19; p=0.0001). The PA clinical subgroups were also evaluated separately, revealing additional statistical relations: ‘fast’ PA and CaexPA differed significantly in p16Ink4a expression (χ2 (2)=8.06; p=0.01781) while ‘slow’ PA and CaexPA did not (χ2 (2)=3.09; p=0.2129). 3-year, 5-year and 10-year survival among p16Ink4a positive CaexPA patients was 100%, 90.56% and 60.37%, respectively, and in CaexPA patients with borderline p16Ink4a expression was 90.0%, 73.64% and 22.20%, respectively. Statistically significant difference between expression pattern and survival rate was observed (F Cox test – F (16, 24)=2.31; p=0.03075).ConclusionsOur study confirms no p16Ink4a expression in normal tissue, but reveals differences in expression between ‘fast’ and ‘slow’ PA. We suggest that p16Ink4a overexpression is connected to PA proliferation and subsequent malignant transformation to CaexPA. Borderline p16Ink4a staining correlates with worse prognosis of CaexPA.

scholarly journals Loss of P16 in Esophageal Adenocarcinoma Detected by Fluorescence in situ Hybridization and Immunohistochemistry

2017 ◽  
Vol 44 (2) ◽  
pp. 14-19
Author(s):  
A. Kotzev ◽  
M. Kamenova
Keyword(s):  
In Situ Hybridization ◽  
Protein Expression ◽  
Fluorescence In Situ Hybridization ◽  
Esophageal Adenocarcinoma ◽  
Allelic Loss ◽  
P16 Gene ◽  
Gene Deletions ◽  
Male Predominance ◽  
P16 Protein

AbstractMolecular biology of esophageal adenocarcinoma (EAC) is not fully elucidated. The aim of this study was to assess the expression of cycle regulator and tumor suppressor p16 in esophageal adenocarcinoma. The expression of p16 at protein and gene level was investigated using immunohistochemistry and fluorescence in situ hybridization in thirteen EAC specimens obtained by endoscopic biopsies and surgical resections. The mean age of enrolled patients was 62 years and a male predominance was observed. Loss of p16 protein expression was detected in 77% of the cases and loss of p16 gene was found in 69% of cases as hemizygous deletion was the most common. Significant correlation was found between the absence of p16 protein expression and p16 allelic loss. Cell cycle disturbances seem to play role in the EAC carcinogenesis and probably p16 gene deletions are connected with the loss of p16 protein expression.

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