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2.
Med Mol Morphol ; 46(4): 225-32, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23471757

ABSTRACT

Acquired cystic disease-associated renal cell carcinoma (ACD-RCC) is a subtype of renal cell carcinoma (RCC) with unique morphologic features found exclusively in the background of end-stage renal disease. We analyzed the clinicopathologic features and immumoreactive profiles of 12 cases of ACD-RCC to further characterize this recently recognized entity. Review of histologic slides was performed in conjunction with immunohistochemical staining directed to the contemporary diagnostic antibodies and the putative target therapy-related markers. Histologically, the tumors showed characteristic inter-or intracellular microlumens and eosinophilic tumor cells. Intratumoral hemosiderin deposition and degenerating foamy tumor cells were consistent findings which were not previously described. Immunohistochemically, all the tumors were positive for alpha-methylacyl-CoA-racemase, CD10, pan-cytokeratin, PTEN (phosphatase and tensin homolog deleted on chromosome 10) and c-met, while negative for carbonic anhydrase-9, CD57, CD68, c-kit, pax-2, platelet-derived growth factor receptor (PDGFR)-α or vascular endothelial growth factor receptor (VEGFR)-2. Heterogenous staining was found for CK7 and kidney-specific cadherin. Positive reaction to c-met suggests its utility as a plausible therapeutic target in ACD-RCC. Thus, we present the unique morphologic and immunopathologic features of ACD-RCC, which may be helpful in both diagnostic and therapeutic aspects.


Subject(s)
Carcinoma, Renal Cell/pathology , Kidney Failure, Chronic/pathology , Kidney Neoplasms/pathology , Adult , Aged , Biomarkers, Tumor/metabolism , Carcinoma, Renal Cell/etiology , Carcinoma, Renal Cell/metabolism , Female , Humans , Keratins/metabolism , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/metabolism , Kidney Neoplasms/etiology , Kidney Neoplasms/metabolism , Male , Middle Aged , Neprilysin/metabolism , Proto-Oncogene Proteins c-met/metabolism , Racemases and Epimerases/metabolism
3.
Diagn Mol Pathol ; 15(2): 74-82, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16778587

ABSTRACT

The cell cycle inhibitor, p16INK4a may be a useful surrogate biomarker of cervical intraepithelial neoplasia (CIN); however, there is currently no consensus of p16INK4a genetic alterations throughout the multiple step process of CIN. Our goal was to identify the methylation frequency of p16INK4a in each step of CIN that is associated with human papillomavirus (HPV) infection, using several different detection methods of p16INK4a methylation to correlate the data. The present study included a total of 43 patients, including 38 with CIN, and 5 normal patients. Three different methods were used to detect hypermethylation of CpG islands, methylation-specific PCR (MSP) amplification of different primer sets of M1, M2, and M3, pyrosequencing of each forward primer region, and immunohistochemistry of p16INK4a. Analysis of MSP showed that 20 of the 38 CIN patients (52.6%) revealed hypermethylation in at least 1 primer set of the p16INK4a promoter. A complete loss of p16INK4a protein expression was observed in 11 cases (28.9%). There was no observed association of methylation of the p16INK4a gene with either CIN grading (P=0.0698) or HPV status (P=0.2811): specifically 42.9% (3/7) was found in CIN 1, 57.1% (8/14) in CIN 2, and 52.9% (9/17) in CIN 3. In concordance with immunohistochemistry results, hypermethylation of the p16INK4a promoter was significantly correlated with a lack of p16 protein expression (P=0.0145). All positive peaks from pyrosequencing matched the MSP results, which ranged from 6.3% to 24.5%. In conclusion, p16INK4a gene silencing during CIN was not determined to be a particularly rare event; however, it does not correlate with either HPV status or CIN grading.


Subject(s)
DNA Methylation , DNA, Neoplasm/genetics , DNA, Neoplasm/metabolism , Genes, p16 , Uterine Cervical Dysplasia/genetics , Uterine Cervical Dysplasia/metabolism , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/metabolism , Base Sequence , Case-Control Studies , CpG Islands , Cyclin-Dependent Kinase Inhibitor p16/genetics , Cyclin-Dependent Kinase Inhibitor p16/metabolism , DNA Primers/genetics , Female , Gene Silencing , Humans , Immunohistochemistry , Molecular Sequence Data , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Papillomaviridae/classification , Papillomaviridae/isolation & purification , Polymerase Chain Reaction , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/virology , Uterine Cervical Dysplasia/pathology , Uterine Cervical Dysplasia/virology
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