Clinicopathologic and Molecular Features of CDX2-/CK20-/MSI+ Colorectal Cancer
Jung Ho Kim, Ye-Young Rhee, Jeong Mo Bae, Nam-Yun Cho, Gyeong Hoon Kang. Seoul National University College of Medicine, Seoul, Republic of Korea; SMG-SNU Boramae Medical Center, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
Background: CDX2 and CK20 are intestinal differentiation-associated proteins and useful diagnostic markers for colorectal-origin carcinomas. Several previous studies have reported that CDX2-negative (CDX2-) and/or CK20-negative (CK20-) colorectal cancers (CRCs) were related to microsatellite instability-positive (MSI+) phenotype. We investigated clinicopathologic and molecular features of CDX2-/CK20-/MSI+ CRC.
Design: Immunostaining for CDX2 and CK20 were performed in a total of 109 MSI+ CRC tissue samples, which had been curatively resected at Seoul National University Hospital, Seoul, Korea from 2004 to 2007. Clinical, pathological and molecular data, including age, gender, tumor location, AJCC stage, tumor differentiation, mucinous histology, lymphocytic reaction, MLH1/MSH2 expression, KRAS/BRAF mutations and CpG island methylator phenotype (CIMP) status, were collected. Clinicopathologic characteristics and prognostic implications of loss of CDX2/CK20 expression were statistically analyzed in 109 MSI+ CRCs.
Results: Simultaneous loss of CDX2/CK20 expression (CDX2-/CK20-) was observed in nine out of 109 MSI+ CRCs (8.3%). CDX2-/CK20- phenotype of MSI+ CRC was significantly correlated with elderly patients (p=0.014), stage III or IV (p=0.049), poorly differentiated histology (p<0.001), BRAF V600E mutation (p=0.02) and CIMP-positive status (p<0.001). CDX2-/CK20- group showed worse overall and disease-free survival compared with the CDX2+ and/or CK20+ group in MSI+ CRC patients (all p<0.001). In multivariate analysis for disease-free survival, CDX2-/CK20- status was independently associated with poor prognosis (p=0.03).
Conclusions: CDX2-/CK20- phenotype of MSI+ CRC was closely associated with old age, high stage, poor differentiation, BRAF mutation and CIMP. CDX2/CK20 loss is an independent poor prognostic factor for MSI+ CRC.
Monday, March 4, 2013 1:00 PM
Poster Session II # 124, Monday Afternoon