[726] Serrated Pathway Colorectal Carcinoma without Microsatellite Instability Demonstrates Aggressive Features and Is Associated with Poor Overall Survival

Christophe Rosty, Joanne P Young, Michael D Walsh, Rhiannon Walters, Mark A Jenkins, Aung Ko Win, Melissa C Southey, Susan Parry, John L Hopper, Graham G Giles, Dallas R English, Daniel D Buchanan. Queensland Institute of Medical Research, Brisbane, Australia; University of Queensland, Brisbane, Australia; Envoi Pathology, Brisbane, Australia; Sullivan Nicolaides Pathology, Brisbane, Australia; University of Melbourne, Melbourne, Australia; Middlemore Hospital, Auckland, Australia; Cancer Council Victoria, Melbourne, Australia

Background: The serrated pathway of colorectal carcinoma (CRC) is primarily defined by BRAF mutation. Within the BRAF-mutated subset of CRC, the microsatellite instability (MSI) phenotype divides the tumours into MSI-H CRC and microsatellite stable (MSS) CRC. MSS BRAF-mutated CRC are reported to be associated with poor prognosis.
Design: We analyzed the available data regarding clinical, pathologic and molecular features of BRAF-mutated CRCs from the Melbourne Collaborative Cohort Study. The features of BRAF-mutated MSS CRCs were compared with BRAF-mutated MSI-H CRCs using two-sided chi-square tests or t-test. Survival curves were plotted using the Kaplan-Meier method and a multivariate Cox regression analysis was performed to determine hazard ratio (HR).
Results: There were 127/765 CRCs with BRAF mutation (17% of all CRCs). Of those, 74 (56%) were MSS. Compared to MSI-H BRAF-mutated CRC, MSS BRAF-mutated CRC were significantly different for the following features:

 BRAF-mutated MSS CRC n = 74BRAF-mutated MSI-H CRC n = 53P value
Mean age at diagnosis (years)68.072.70.001
Distal colonic location39/72 (54%)5/50 (10%)<0.001
Mucinous differentiation4/67 (6%)14/37 (30%)<0.001
Tumor budding30/57 (53%)8/45 (18%)<0.001
Venous invasion17/67 (25%)3/49 (6%)0.007
Metastatic lymph nodes45/66 (68%)16/51 (31%)<0.001
P53 overexpression41/69 (59%)9/45 (20%)<0.001
CIMP phenotype25/68 (37%)37/48 (77%)<0.001


Patients with BRAF-mutated MSS CRC had a significantly poorer overall survival compared with patients with BRAF-mutated MSI CRC (HR = 2.5; 95%CI 1.44 - 4.40; P = 0.001).


Conclusions: BRAF-mutated MSS CRCs arise predominantly in the distal colon and show aggressive pathologic features, frequent p53 alteration and poor overall survival. This subtype of CRC, and potentially the polyps from which they develop, should be identified by pathologists with more readily available methods to routinely detect BRAF mutation.
Category: Gastrointestinal

Monday, March 4, 2013 8:30 AM

Proffered Papers: Section D, Monday Morning

 

Close Window