Characterization of Rectal, Proximal and Distal Colon Cancers Based on Clinicopathological, Molecular and Protein Profiles
P Minoo, I Zlobec, M Peterson, L Terracciano, A Lugli. University of California San Diego, San Diego, CA; Institute of Pathology, University Hospital of Basel, Basel, Switzerland
Background: Accumulating evidence suggests that colorectal cancer should be viewed as a heterogeneous disease, with proximal and distal colorectal cancers showing multiple biological and clinical differences. The aim of this study was to perform a clinicopathological, molecular and protein characterization of proximal and distal colon carcinomas and rectal cancers in order to develop a profile of these tumors and thus providing insight into their pathogenesis and oncogenic behavior.
Design: 399 colorectal cancer patients were evaluated for clinicopathologic and molecular features including K-RAS, BRAF and MSI status. These tumors were also screened for expression of 36 tumor-associated and 14 lymphocyte/inflammatory-associated protein markers.
Results: Proximally located tumors show significantly larger tumor size, higher T-stage, higher tumor grade (p<0.001 each) and more frequent mucinous histologic subtype (p=0.038) compared to the distal colon and rectum. The frequency of BRAF mutation and MSI-high phenotype were significantly higher in proximal colon cancers (p=0.002 each). Expression of 11 tumor-associated markers (CDX2, CD44v6, CD44s, TOPK, nuclear beta-catenin, pERK, APAF-1, E-Cadherin, MUC2, p21 and bcl2) and 4 tumor immunologic markers (CD68, CD163, FoxP3 and TIA-1) was found to be significantly different between rectum, left- and right-sided tumors. In multivariate analysis CD44s, CD44v6, nuclear beta-catenin and CD68 expression was found to best discriminate left- versus right sided colon cancers (p=0.037, p<0.001, 0.001 and 0.017). Tumor diameter, pT stage and MSI status best distinguish right-sided colon cancers from rectal cancers (p=0.005, 0.002 and 0.033) and pT stage and E-Cadherin best discriminate left-sided colon cancers and rectal cancers (p=0.004 and 0.016).
Conclusions: Rectal cancers, proximal and distal colon cancers vary significantly with respect to their clinicopathological, molecular characteristics and protein expression profiles. This data along with existing evidence for the presence of distinct regional embryological origin and gene expression profile is highly supportive of the concept that proximal and distal CRCs are distinct clinicopathologic entities. This concept has practical implications in prevention and treatment of both familial and sporadic CRCs.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 99, Monday Morning