title: Colorectal cancers with both p16 and p14 methylation show invasive characteristics.
abstract: Recent studies indicated that p16 and p14 inactivation owing to promoter methylation was important for colorectal tumorigenesis. In this study, we examined the methylation status of these genes in 86 primary colorectal cancers using methylation-specific PCR (MSP) and correlated the results with the clinicopathological features of the patients. Aberrant promoter methylation of p16 and p14 genes was detected in 43 of 86 (50%) and 25 of 86 (29%) colorectal cancers, respectively. Next, we examined the correlation of methylation status with the clinicopathological features. We found a significant difference in maximal tumor size (P=0.022) when patients with both p16 and p14 methylation were compared to other patients. On the other hand, there was no significant difference in other factors, such as the extent of tumor and Dukes stage. These results suggested that colorectal cancer with both p16 and p14 methylation has the same invasiveness at a smaller size compared to that of the cancer with neither p16 nor p14 methylation. Inactivation of both p16 and p14 genes may result in a malignant change in colorectal cancer cells, leading to advanced cancers with a smaller size than those with p16 or p14 activity.
authors.affiliation: Second Department of Surgery, Nagoya University School of Medicine, Showa-ku, Nagoya 466-8550, Japan. khibi@med.nagoya-u.ac.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Hibi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakayama
authors.forename: Masahiko
authors.initials: M
authors.lastname: Koike
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kasai
authors.forename: Katsuki
authors.initials: K
authors.lastname: Ito
authors.forename: Seiji
authors.initials: S
authors.lastname: Akiyama
authors.forename: Akimasa
authors.initials: A
authors.lastname: Nakao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis* / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D015801:Helminth Proteins / Q000096:biosynthesis* / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics*; D009361:Neoplasm Invasiveness; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D013447:Sulfites / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D000096985:Calponins
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D015801:Helminth Proteins; D009124:Muscle Proteins; D013447:Sulfites; C118619:calponin homolog protein, Schistosoma japonicum; D000096985:Calponins