ABSTRACT
CONTEXT: Inflammatory pseudotumor is a rare benign lesion that can occur at a wide variety of primary sites. It is usually worrisome for the patient and the medical staff, since it cannot be clinically or radiologically distinguished from malignant entities. CASE REPORT: We report on a case of splenic inflammatory pseudotumor presenting with concomitant renal cell carcinoma. Despite the alarming macroscopic appearance of pseudotumors, their microscopic features usually confirm the inflammatory nature of such lesions. Evidence regarding the etiology of pseudotumors is still lacking, but hypotheses have been created.
Subject(s)
Carcinoma, Renal Cell/pathology , Granuloma, Plasma Cell/pathology , Kidney Neoplasms/pathology , Neoplasms, Multiple Primary/pathology , Splenic Diseases/pathology , Aged , Diagnosis, Differential , Humans , Immunohistochemistry , Male , Photomicrography , Tomography, X-Ray ComputedABSTRACT
Epigenetic change such as DNA methylation is one important mechanism for regulating gene expression as genetic change, such as mutation or loss of heterozygosity. Methylation of cancer-related genes has been shown to play an important role in carcinogenesis and tumor progression. Using methylated CpG island amplification (MCA)/representational difference analysis (RDA), we identified four CpG islands in neurotrophin tyrosine kinase receptor type 2 (NTRK2), Protocadherine Flamingo1 and MFPC (Methylated Fragments in Prostate Cancer) 7 and 8. Bisulfite sequencing revealed that 2 regions of NTRK2 as well as MFPC7 and MFPC8 were aberrantly methylated in prostate cancer cell lines, and COBRA showed that 48 (76.24%), 37 (58.7%) and 14 (22.2%) of 63 prostate cancer tissues were methylated, respectively, for these sites. On the other hand, none of 13 benign prostate samples were methylated, except for 1 (7.7%) with NTRK2. For NTRK2, mRNA expression was negative in prostate cancer cell lines (LNCaP and DU145) but was recovered on a methyltransferase inhibitor (5-Aza-CdR) treatment. The role of NTRK2 within NTRK remains unclear. Our results suggest that these 3 hypermethylated DNA fragments also may be markers of prostate cancer detection.
Subject(s)
CpG Islands/genetics , DNA Methylation , Gene Expression Regulation, Neoplastic , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Animals , Biomarkers, Tumor/analysis , Gene Amplification , Male , Tumor Cells, CulturedABSTRACT
Carcinogenesis of the prostate involves androgen influences, and associations between genetic polymorphisms of androgen receptor and metabolizing enzymes and prostate cancer risk have been reported. Roles for non-androgenic hormones are not well defined, but they also may have an impact judging from epidemiological and animal experimental alphalambda zeta of data. The purpose of the study was to determine whether hormone-related polymorphisms are associated with prostate cancer risk. A case-control study was performed with 147 Japanese prostate cancer patients and 266 urological controls. Polymorphisms of target genes [cytochrome P450 (CYP) 1B1, Leu432Val; debrisoquine hydroxylase, (CYP2D6)*4; aromatase (CYP19), Arg264Cys; estrogen receptor (ER)alpha-Xx (Xba I) and Pp (Pvu II); ERbeta-Rr (Rsa I); progesterone receptor (PR) Alu in intron 7] were examined by PCR-based methods. The capital and small letters signify the absence and presence of restriction sites, respectively. Odds ratios (OR) were adjusted for age using multiple logistic regression analysis with SPSS Medical Pack. Among the seven examined genetic polymorphisms, significant associations between CYP1B1 Leu432Val (OR 4.80; 95% confidence interval (CI), 1.21-19.05) and Alu in intron 7 of PR (OR 4.17; 95%CI, 1.26-13.85) were found. As for combined effects, the CYP1B1 polymorphisms (Leu/Val+Val/Val) together with heterozygosity for Alu in the PR were more frequent among prostate cancer patients (1.45%) than controls (0.41%), although without significance (OR, 3.99; 95%CI, 0.36-44.8). The combination of ERalpha (P/p+p/p) polymorphisms with heterozygosity for Alu in the PR demonstrated an OR of 4.56 (95%CI, 1.01-20.6). This pilot study showed that CYP1B1 and PR polymorphisms, alone or in combination, might be associated with prostate cancer risk. They might, therefore, have potential as a tool for identifying high-risk individuals.
Subject(s)
Cytochrome P-450 Enzyme System/genetics , Prostatic Neoplasms/genetics , Receptors, Estrogen/genetics , Receptors, Progesterone/genetics , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Alleles , Case-Control Studies , Genetic Predisposition to Disease , Genotype , Humans , Isoenzymes , Japan , Male , Polymerase Chain Reaction , Polymorphism, Genetic , Prostatic Neoplasms/pathologyABSTRACT
CONTEXTO: Pseudotumor inflamatório é uma lesão benigna rara que pode se desenvolver em uma grande variedade de órgãos. Sua grande importância na prática médica reside na enorme dificuldade de distingui-lo tanto clinicamente quanto radiologicamente de condições malignas. RELATO DE CASO: Os autores relatam um caso de pseudotumor envolvendo o baço e apresentando-se concomitantemente a um carcinoma renal de células claras. Apesar da semelhança macroscópica a tumores malignos, as características inflamatórias do pseudotumor são facilmente evidenciadas à microscopia. Apesar de hipóteses terem sido formuladas, os mecanismos patogenéticos relacionados ao pseudotumor ainda não estão bem estabelecidos.
Subject(s)
Humans , Male , Aged , Carcinoma, Renal Cell/pathology , Granuloma, Plasma Cell/pathology , Kidney Neoplasms/pathology , Splenic Diseases/pathology , Carcinoma, Renal Cell/complications , Diagnosis, Differential , Granuloma, Plasma Cell/complications , Immunohistochemistry , Kidney Neoplasms/complications , Photomicrography , Splenic Diseases/complications , Tomography, X-Ray ComputedABSTRACT
Transcriptional silencing of cancer-related genes by DNA methylation is observed in various cancers. To identify genes controlled by methylation in prostate cancer, we used cDNA microarray analysis to investigate gene expression in prostate cancer cell lines LNCaP and DU145 treated with a methyltransferase inhibitor alone or together with a histone deacetylase inhibitor. We detected significant changes (3.4-5.7%) in gene expression in prostate cancer cell lines with the drug treatments. Among the affected genes, that for the vascular endothelial growth factor receptor 1 (VEGFR-1) was re-expressed in LNCaP and DU145 after the drug treatments. Bisulfite sequencing revealed the promoter and exon 1 of the VEGFR-1 to be hypermethylated in the cell lines. These results support the idea that methylation is associated with loss of VEGFR-1 mRNA expression in prostate cancer cell lines. Combined bisulfite restriction analysis (COBRA) showed the gene to be methylated in 24 (38.1%) of 63 primary local prostate cancer samples, while in all 13 benign prostate samples it was not. These findings indicate that methylation of VEGFR-1 is related with prostatic carcinogenesis.
Subject(s)
Azacitidine/analogs & derivatives , DNA Methylation , Gene Expression Regulation, Neoplastic , Prostatic Hyperplasia/genetics , Prostatic Neoplasms/genetics , Vascular Endothelial Growth Factor Receptor-1/genetics , Antimetabolites, Antineoplastic/pharmacology , Azacitidine/pharmacology , Decitabine , Enzyme Inhibitors/pharmacology , Gene Expression Profiling , Gene Expression Regulation, Neoplastic/drug effects , Histone Deacetylase Inhibitors , Humans , Hydroxamic Acids/pharmacology , Male , Oligonucleotide Array Sequence Analysis , Polymerase Chain Reaction , Promoter Regions, Genetic , Prostatic Hyperplasia/pathology , Prostatic Neoplasms/pathology , Sulfites , Tumor Cells, CulturedABSTRACT
The expression of c-myc and p-ras-21 oncogenes was studied using an immunohistochemical method with monoclonal antibodies in 126 samples of gallbladder carcinoma (103 primary tumors and 23 metastatic lesions). Twenty five gallbladder samples without tumor evidence were used as controls. C-myc oncoprotein was positive in one control sample and p-ras-21 oncoprotein was negative in all. Among primary carcinomas c-myc was positive in 9 (9 per cent) and 4 (4 per cent); among metastatic carcinomas c-myc was positive in 6 (26 per cent, p=0.03 vs primary carcinoma) and p-ras-21 in 11 (48 per cent, p <0.001 vs primary carcinoma). There was a non significant association between c-myc and p-ras-21 expression and degree of histological differentiation and levelñ of tumoral infiltration. It is concliuded that c-myc and p-ras-21 oncoprotein expression is observed in less than 10 per cent of primary gallbladder carcinomas and that this expression is significantly higher in metastatic cells
