Article Figures & Data
Figures
- Fig. 1.
Representative examples of MSP analyses of the methylated form (M) of four genes: CDH1, RASSF1A, APC, and CDH13. Amplification of unmethylated form of p16INK4A (p16U) was used as a control for DNA integrity. Across top of figure: M, size marker; T, tumor samples 1 through 10; N, negative control.
- Fig. 2.
Correlation of methylation findings and risk factors. For each panel, the methylation percentages are presented as correlated with a risk factor. Right side of each panel, the corresponding MIs. A, correlation with histological grade. Transitional cell tumors were divided into a low-grade (grades 1 or 2) group or a high-grade (grade 3) group. The single squamous cell carcinoma was omitted from the analysis. B, correlation with growth pattern (papillary or nonpapillary). C, correlation with presence or absence of muscle invasion. D, correlation with tumor stage. Tumors were divided into a low-stage (stage 0-II) group or a high-stage (stage III-IV) group. Tumor stage status was available for only 63 of the tumors. E, correlation with ploidy status of the tumor (diploid or aneuploid). Ploidy status was available for only 47 of the tumors. F, correlation with a number of factors of increased risk. Tumors were divided into a group with zero to two factors or a group with three to five factors (A–E, the risk factors).
- Fig. 3.
Correlation of methylation status and patient survival by the Kaplan-Meier method. A, survival curves by methylation status of CDH1. B, survival curves by methylation status of FHIT. C, survival by MI (median value, 0.2). To get approximately equal numbers in each group, cases were divided into a high-MI group (MI, ≥0.2) and a low-MI group (MI, ≤0.1). D, survival curves by methylation status of APC.
Tables
- Table 1
Summary data of genes tested
Gene abbreviation Gene name Chromosomal location Reference for methodology Other key references FHIT Fragile histidine triad 3p14 (26) RASSF1A RAS association domain family protein 1A 3p21 (16) (17) RARβ Retinoic acid receptor β 3p24 (27) APC Adenomatous polyposis coli 5q21 (28) p16 INK4A Cyclin-dependent kinase inhibitor 2A 9p21 (8) DAPK Death-associated protein kinase 9q34 (29) (30) MGMT O6-methylguanine-DNA-methyltransferase 10q26 (31) GSTP1 Glutathione S-transferase P1 11q13 (32) a CDH1 E-cadherin 16q22 (33) CDH13 H-cadherin 16q24 (22) (23) -
a We modified the annealing temperature of the methylated form from 59° C to 64° C.
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- Table 2
Multivariate statistics of survival
Variable Hazards ratio 95% confidence interval P Tumor grade, high (grade 3)/low (grades 1 or 2) 1.45 0.37–5.75 0.59 Growth pattern, nonpapillary/papillary 0.80 0.25–2.52 0.70 Muscle invasion, invasive/noninvasive 0.98 0.29–3.32 0.97 CDH1 methylation 3.30 1.20–9.11 0.02 RASSF1A methylation 1.12 0.36–3.48 0.85 APC methylation 1.95 0.62–6.15 0.25 CDH13 methylation 1.23 0.43–3.49 0.70 FHIT methylation 1.66 0.55–4.99 0.37 MI, high MI/low MI 1.05 0.20–5.41 0.95
Volume 61, Issue 24
