cyclin-d1 and Carcinoma--Mucoepidermoid

Although mucoepidermoid carcinoma of the salivary gland is relatively common, mucoepidermoid carcinoma arising from the mucous glands of the bronchus is rare. Bronchial mucoepidermoid carcinoma usually presents as an intraluminal mass producing luminal occlusion. Symptoms are airway obstruction and recurrent pneumonia. Macroscopically, mucoepidermoid carcinoma appears as an exophytic intrabronchial mass with intact or ulcerated bronchial mucosa. Microscopically, the tumors are located in the submucosa of the large bronchi. The tumors are usually well differentiated and contain a combination of mucus-secreting, squamous, and intermediate cells. The increased frequency of this tumor in the pediatric population suggests a genetic abnormality. Recent genetic studies have demonstrated reciprocal chromosomal translocations including t(1;11)(p22;q13), t(11;19)(q14-21;p12), and t(11; 19)(q21;p13). Chromosome 11 in the first translocation appears to have been altered resulting in up-regulation of the cyclin D1 gene and overexpression of cyclin D1. The t(11;19)(q21;p13) encodes a novel fusion product capable of disrupting the Notch signaling pathway.

Topics: Bronchi; Bronchial Neoplasms; Carcinoma, Mucoepidermoid; Cyclin D1; Diagnosis, Differential; Gene Expression Regulation, Neoplastic; Humans; Respiratory Mucosa; Translocation, Genetic

Salivary gland tumors are complex and have a great histomorphological diversity; more than 30 histological subtypes are currently described and the study of proteins that help understand and differentiate these tumors is essential. We aimed to analyze the immunoexpression of cyclooxygenase-2 (COX-2) and cyclin D1 proteins in pleomorphic adenomas (PA), mucoepidermoid carcinomas (MEC) and adenoid cystic carcinomas (AdCC) of salivary glands.. A total of 38 PA, 12 AdCC and 12 MEC underwent immunohistochemical study by the polymeric biotin-free technique. Immunopositive cells were analyzed semi-quantitatively. For statistical analysis, a significance level was set at p ≤ 0.05.. Overall, these tumors were more prevalent in women (n = 37). The mean age of these patients was 58-year-old and the parotid gland was the most affected anatomic site (n = 33). All cases of AdCC and MEC showed immunopositivity to cyclin D1; however, 39.5% of the PAs were negative (p < 0.001). Regarding COX-2 immunoexpression, we observed that all cases of CME were positive, whereas 60.5% of the PA and 75% of the CAC analyzed were completely negative (p = 0.042).. The overexpression of COX-2, observed only in MEC, emphasizes that salivary gland tumors have different profiles. Cyclin D1 is more immunoexpressed in malignant tumors. Together, these immunohistochemical findings may be useful in differentiating the studied tumors.

Topics: Adenoma, Pleomorphic; Adult; Biomarkers, Tumor; Carcinoma, Adenoid Cystic; Carcinoma, Mucoepidermoid; Cyclin D1; Cyclooxygenase 2; Female; Humans; Male; Middle Aged; Salivary Gland Neoplasms

Primary lung tumors are rare in children, and mucoepidermoid carcinoma (MEC) represents less than 10% of them. Additionally, MEC arising from bronchogenic cysts (BC) is particularly unusual. We describe the clinical and genetic findings on a MEC occurring within a previous location of a BC in an adolescent. This particular association has not been previously reported. The lesion revealed normal karyotype without the typical t(11;19)(q21;p13) translocation. Cyclin D1 overexpression (165-fold increase) was demonstrated by real-time PCR although FISH assessment showed normal hybridization at 11q13. Information on these unusual clinical presentations may present relevant insight on tumorigenesis of infrequent pediatric pulmonary tumors.

Topics: Adolescent; Bronchogenic Cyst; Carcinoma, Mucoepidermoid; Child; Cyclin D1; Female; Gene Expression; Humans; Immunohistochemistry; Lung Neoplasms; Reverse Transcriptase Polymerase Chain Reaction

Cytoplasmic and nuclear accumulation of beta-catenin in mucoepidermoid carcinoma (MEC) is frequently noted, but the mechanism is unknown.. The methylation status of adenomatous polyposis coli (APC) and secreted frizzled-related proteins (SFRPs) was examined by methylation-specific polymerase chain reaction (MSP) assay. The association of SFRP1, beta-catenin, and cyclin D1 expression in MEC was evaluated by immunohistochemical staining.. A high percentage of methylation in APC and the SFRP genes was found in MEC compared with adjacent normal tissues, in which SFRP1 (58.6%) was the most frequent methylated gene. Moreover, abundant expression of SFRP1 was noted in normal tissues, whereas reduced SFRP1 expression was detected in 71.7% (33/46) of MECs. There was significant association between methylation and reduced expression of SFRP1. Cytoplasmic/nuclear (C/N) beta-catenin and high cyclin D1 expression were found in 13/55 (23.6%) and 36/55 (65.5%) of cases, respectively. There was significant correlation between C/N beta-catenin expression and reduced SFRP1 expression (P = 0.009). In addition, SFRP1 and beta-catenin expression correlated with tumor malignancy index such as tumor grade and stage. Overall patient survival was significantly worse in patients with reduced SFRP1 and C/N beta-catenin expression (P = 0.009 and P = 0.002, respectively).. Methylation of the SFRP1 gene was the major cause of reduced SFRP1 expression. Reduced SFRP1 led to C/N accumulation of beta-catenin and was associated with tumor malignancy. Therefore, examination of SFRP1 expression and beta-catenin location could be useful predictors of tumor progression and prognosis in patients with MEC.

Topics: Adenomatous Polyposis Coli; beta Catenin; Biomarkers, Tumor; Carcinoma, Mucoepidermoid; Cell Line, Tumor; Cyclin D1; Female; Humans; Intercellular Signaling Peptides and Proteins; Male; Membrane Proteins; Methylation; Neoplastic Processes; Polymerase Chain Reaction; Prognosis; Salivary Gland Neoplasms; Survival Analysis

Nuclear/cytoplasmic accumulation of beta-catenin is mainly regulated by its degradation, which is initiated by interaction with adenomatous polyposis coli (APC) protein. Accumulation of beta-catenin activates the transcription of 1 of the target oncogenic genes, cyclin D1, in the Wnt/Wingless pathway. The role of beta-catenin and cyclin D1 in this pathway has not been previously studied in head and neck mucoepidermoid carcinoma (MEC). This study investigates abnormalities of beta-catenin and the APC gene in MEC and correlates the patterns of cyclin D1 overexpression and nuclear/cytoplasmic accumulation of beta-catenin with the clinical outcome.. Mutations of the beta-catenin and APC genes, as well as overexpression of cyclin D1, were investigated by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) in tissue samples from 44 cases of MEC. In addition, we employed differential PCR method to detect amplification of the cyclin D1 gene. Furthermore, the overexpression of cyclin D1 and nuclear/cytoplasmic accumulation of beta-catenin was examined by immunohistochemistry, and any correlation with clinicopathologic parameters was evaluated.. Nuclear/cytoplasmic accumulation of beta-catenin was observed in 6 of 44 MEC cases (13.6%), 5 of which were high-grade MEC, while the other 1 case was intermediate-grade tumor. Mutational analysis of exon 3 of the beta-catenin gene revealed that 4 of 26 cases (15.4%) contained point mutations (3 in codon 32, GAC [Asp] to GGC [Gly]; 1 in codon 42, ACA [Thr] to ATA [Ile]), and all these 4 cases showed beta-catenin accumulation immunohistochemically. The nuclear/cytoplasmic accumulation of beta-catenin was significantly correlated with the adverse outcome of patients (p = .011). Two APC gene alterations were detected in 2 cases of low-grade MEC, where there was no beta-catenin nuclear accumulation. Amplification of the cyclin D1 gene was observed in 10 of 26 cases (38.5%). Cyclin D1 overexpression was recognized in 19 of 44 cases (43.2%) and was significantly correlated with beta-catenin accumulation (p = .003).. These findings suggest that beta-catenin, which, in cooperation with cyclin D1, plays crucial role in the Wnt-signaling pathway, may also contribute to the adverse outcome and high-grade tumor staging of MEC.

Topics: Adult; Aged; Aged, 80 and over; beta Catenin; Carcinoma, Mucoepidermoid; Codon; Cyclin D1; Disease Progression; Exons; Female; Genes, APC; Head and Neck Neoplasms; Humans; Immunohistochemistry; Male; Middle Aged; Point Mutation; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Survival Analysis

To analyze the expression of beta-catenin and cyclin D1 in mucoepidermoid carcinoma (MEC) of variable histologic grades to establish a correlation between the expression of these proteins and the different histopathologic grades of this neoplasia.. Immunohistochemical analysis of MEC.. Pathological Anatomy Service, Discipline of Oral Pathology, Department of Dentistry, Federal University of Rio Grande do Norte, Natal, Brazil.. Fifteen cases of MEC, graded and categorized according to criteria reported in the literature into 5 tumors with a low grade of malignancy, 4 with an intermediate grade, and 6 with a high grade.. Labeling patterns of beta-catenin and cyclin D1.. No significant difference in beta-catenin labeling patterns was observed between low- and intermediate-grade tumors or between low- and high-grade tumors (P = .60 and P = .06, respectively; Fisher exact test), despite a strong tendency toward a difference in the latter. In contrast, a significant difference was noted between intermediate- and high-grade tumors (P = .03). For cyclin D1, no labeling was observed in any high-grade cases, and only 3 cases showed overexpression of this protein. Comparison of the labeling patterns among the different histologic grades revealed no significant difference.. The reduced expression of beta-catenin observed in all high-grade MECs is probably due to the loss of its adhesion function, which confers a greater invasive potential to these tumors. The overexpression of cyclin D1 observed in only 3 MEC cases suggests that this protein does not participate in the etiopathogenesis of these tumors, which implies that other genes are likely responsible.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; beta Catenin; Carcinoma, Mucoepidermoid; Child; Cyclin D1; Cytoskeletal Proteins; Female; Humans; Immunoenzyme Techniques; Male; Middle Aged; Staining and Labeling; Statistics, Nonparametric; Trans-Activators

Topics: Adolescent; Bronchial Neoplasms; Carcinoma, Mucoepidermoid; Chromosomes, Human, Pair 11; Cyclin D1; Cytogenetic Analysis; DNA, Neoplasm; Female; Gene Expression Regulation, Neoplastic; Humans; In Situ Hybridization, Fluorescence; Up-Regulation