Morphological and molecular heterogeneity within nonmicrosatellite instability-high colorectal cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 62; no. 21; pp. 6011 - 6014
• Main Authors: WHITEHALL, Vicki L. J, WYNTER, Coral V. A, WALSH, Michael D, SIMMS, Lisa A, PURDIE, David, PANDEYA, Nirmala, YOUNG, Joanne, MELTZER, Stephen J, LEGGETT, Barbara A, JASS, Jeremy R
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.11.2002
• Subjects: Adaptor Proteins, Signal Transducing; Biological and medical sciences; Carrier Proteins; Colorectal Neoplasms - classification; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Cyclin-Dependent Kinase Inhibitor p16 - genetics; DNA Methylation; DNA-Binding Proteins; Gastroenterology. Liver. Pancreas. Abdomen; Histone-Lysine N-Methyltransferase; Humans; Medical sciences; Microsatellite Repeats - genetics; MutL Protein Homolog 1; Neoplasm Proteins - genetics; Nuclear Proteins - genetics; O-Methylguanine-DNA Methyltransferase - genetics; Prospective Studies; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Transcription Factors; Tumor Suppressor Protein p14ARF - genetics; Tumors; Human; Rectal disease; Nucleotide sequence; Transcription promoter; Biological marker; Malignant tumor; CpG island; Colonic disease; Heterogeneity; Gene silencing; Gene; GC rich sequence; Microsatellite DNA; DNA; Rectum; Molecular epidemiology; Digestive diseases; Intestinal disease; Instability; Colon; Methylation
• ISSN: 0008-5472; 1538-7445

Colorectal cancer (CRC) has traditionally been classified into two groups: microsatellite stable/low-level instability (MSS/MSI-L) and high-level MSI (MSI-H) groups on the basis of multiple molecular and clinicopathologic criteria. Using methylated in tumor (MINT) markers 1, 2, 12, and 31, we stratified 77 primary CRCs into three groups: MINT++ (>2), MINT+ (1-2), and MINT- (0 markers methylated). The MSS/MSI-L/MINT++ group was indistinguishable from the MSI-H/MINT++ group with respect to methylation of p16(INK4a), p14(ARF), and RIZ1, and multiple morphological features. The only significant difference between MSI-H and non-MSI-H MINT++ cancers was the higher frequency of K-ras mutation (P < 0.004) and lower frequency of hMLH1 methylation (P < 0.001) in the latter. These data demonstrate that the separation of CRC into two nonoverlapping groups (MSI-H versus MSS/MSI-L) is a misleading oversimplification.