Differences in loss of p16INK4 protein expression by promoter methylation between left- and right-sided primary colorectal carcinomas.
The p16INK4 gene, encoding a cyclin-dependent kinase inhibitor, is frequently methylated in colorectal cancer, and a side-specific methylation frequency was suggested. To clarify the frequency of real loss of tumor suppressor function dependent on anatomical localization, we investigated 43 primary colorectal carcinomas by determining aberrant promoter methylation using methylation-specific PCR. In addition, we evaluated the p16INK4 protein expression immunohistochemically. P16INK4 methylation was found in 18 of 43 (41.9%) cases. Fourteen of 43 cases (32.6%) were negative for p16INK4 protein, whereas 10 of these 14 cases showed methylation of the promoter region of the p16INK4 gene. Methylation of the promoter region was significantly correlated with loss of p16INK4 protein (p<0.01). P16INK4 tumor suppressor inactivation was significantly correlated with proximal location (p=0.031 for methylation and p=0.028 for immunostaining). The groups characterized by tumors with and without aberrant promoter methylation or loss of p16INK4 immunostaining showed no significant difference in either Dukes' stage and grade or age and gender. This is further evidence that p16INK4 methylation causes gene silencing. Loss of p16INK4 tumor suppressor function in colorectal tumors was associated with proximal location in the gut.
Schneider-Stock
Regine
R
Department of Pathology, Medical Faculty, Otto-von-Guericke University, 39120 Magdeburg, Germany.
Boltze
Carsten
C
Peters
Brigitte
B
Höpfner
Tino
T
Meyer
Frank
F
Lippert
Hans
H
Roessner
Albert
A
D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics*; D002467:Cell Nucleus / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis* / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic
D019941:Cyclin-Dependent Kinase Inhibitor p16