10.6084/M9.FIGSHARE.97899
Salvador J. Diaz-Cano
0000-0003-1245-2859
A Blanes
J Rubio
A Matilla
JJ Sanchez-Carrillo
HJ Wolfe
ARE INTRAUROTHELIAL LESIONS ASSOCIATED WITH MUSCLE-INVASIVE TRANSITIONAL CELL CARCINOMAS TRUE PRECURSORS?
<p>Background: The clonal relationship between low-grade urothelial dysplasia (LGUD) and carcinomas in situ (CIS) with muscle- invasive transitional cell carcinoma (TCC) remains unknown.<br>Methods: LGUD (18) and CIS (12) from 72 patients with muscle-invasive TCC (coexistent lesions in 5 patients) were selected and microdissected. DNA was extracted from dysplastic cells (LGUD and CIS) and invasive tumor cells located above (superficial) and below (deep) the muscularis mucosa and used to analyze the methylation pattern of androgen receptor alleles. The microsatellite patterns of TP53, RBI, WT1, and NFI were studied by PCR-denaturing gradient gel electrophoresis. The same areas were systematically s t u d i a p r the expression of Ki67 and cell cycle regulators (p53, p21 , pRBl), nuclear DNA content, and in situ end labeling. Appropriate controls were run in each case.<br>Results: Monoclonal patterns were revealed in CIS (6, loo%), invasive TCC (13, 100%), and LGUD (2, 20%), whereas polyclonal patterns were observed in LGUD only (8, 80%). CIS showed aneuploid DNA content and more microsatellite loci altered than the corresponding invasive compartments, always involving TP53 loci and expressing abnormal p53. In contrast, LGUD revealed diploid DNA content and microsatellite abnormalities in only 2 cases, one monoclonal (RBI) and one polyclonal (WT1 and NF1). Opposite kinetic patterns were observed for CIS (higher Ki-67 index, lower ISEL index) and LGUD (lower Ki-67 index, higher ISEL index).<br>Conclusions: These genetic findings suggest that CIS evolution is independent of muscle-invasive ?CC and that secondary CIS is not the precursor lesion of coexistent TCC. LGUD should not be closely connected with this molecular progression. The kinetic patterns would contribute to the accumulation of genetic abnormalities in CIS but not in LGU.</p>
Medicine
Molecular Biology
Cancer
Cell Biology
figshare
2012
2012-11-22
2012-11-22
Journal contribution
148502 Bytes
CC BY 4.0