Heterogeneity of Clinicopathological Features in Microsatellite Instability-Positive Colorectal Cancers Depending on CIMP Status.
Jeong-Mo Bae, Jung-Ho Kim, Mi-Jung Kim, Jae-Moon Ko, Nam-Yun Cho, Gyeong-Hoon Kang. Seoul National University Hospital, Republic of Korea; Asan Medical Center, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University, Republic of Korea
Background: Microsatellite instability–positive (MSI+) colorectal cancers (CRCs) are divided into CpG island methylator phenotype–positive (CIMP+) and –negative (CIMP−) tumors. The repertoire of inactivated genes in CIMP+/MSI+ CRCs overlaps with but is likely to differ from that of CIMP−/MSI+ CRCs because CIMP+/MSI+ tumors harbor additional genes that are inactivated by promoter CpG island hypermethylation. Because genotypic differences are likely to be manifested as phenotypic differences, CIMP+/MSI+ CRCs are expected to differ from CIMP−/MSI+ CRCs in some clinicopathological features, which are currently understood poorly. We characterized both common and different features between the two subtypes.
Design: A total of 72 MSI+ CRCs were analyzed for their CIMP status with eight-marker panel MethyLight assay. CIMP+/MSI+ and CIMP−/MSI+ CRCs were compared regarding clinicopathologic features and mutation in KRAS/BRAF.
Results: Eighteen cases (25%) were CIMP+, and this CIMP+ subtype was highly correlated with older age (CIMP+ 94.4% vs. CIMP− 33.3%, age >57) (p < 0.001). Polypoid gross appearance without ulceration was observed only in CIMP−/MSI+ CRCs (10%, p = 0.057). CIMP+/MSI+ CRCs were closely associated with poor differentiation, sheeting appearance, signet ring cell appearance, and acinar-form appearance, whereas the CIMP−/MSI+ subtype was closely associated with intraglandular eosinophilic mucin and stratified nuclei (all p-values < 0.05). The mean count of CD8+ tumor-infiltrating lymphocytes was higher in CIMP+ (51.3/HPF) than CIMP− tumors (36.1/HPF). Patients with CIMP+/MSI+ CRCs showed worse overall survival than patients with CIMP−/MSI+ CRCs.
Conclusions: Our results demonstrate heterogeneity in the clinicopathological features of MSI+ CRCs depending on CIMP status. The observation that CIMP+ and CIMP− subtypes showed different clinical features may provide a clue for establishing subtype-specific therapeutic strategies for these two subtypes.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 52, Wednesday Morning