[667] COX2 and P27 Expression in Young Patients with Colorectal Cancer

BC Kenney, ME Robert, D Jain, KA Mitchell. Yale University School of Medicine, New Haven, CT

Background: Despite an overall decrease in incidence, colorectal cancer (CRC) rates are increasing in patients under 50. Specific pathologic, and now molecular, features have been described in these patients. Recent studies in CRC involving p27 and COX2 expression have shown potential for therapeutic use of COX2 inhibitors. We investigated CRC patients aged <40, <50, and 50-60, and analyzed morphologic data, MLH1 and MSH2 expression and p27 and COX2 staining among subgroups.
Design: Our database was searched for CRC resections in patients <40 (n=20), 40-50 (n=53) and 50-60 (n=89) from 1985-2009. Morphologic data, including tumor grade/differentiation, stage, size and lymph node status were determined from all available slides and reports. MLH1, MSH2, p27, and COX2 immunostains were done in patients <50 and graded on a binary or semi-quantitative scale. Statistical analysis was performed using one-way ANOVA and the f-test.
Results: Compared to reported rates in all CRC, patients <50 had less COX2 staining and greater incidence of MSH2 loss, but similar loss of p27 and MLH1.

MSI and P27 Loss (%)

	<40	40-50	Reported
MSH2	11.8	4.1	1-2
MLH1	11.1	12.5	10-15
P27	12.5	12.2	11-33

COX2 expression (%)

Score	<40	40-50	Reported
0	40	25	16
1+	47	44	19
2+	13	31	65

In our cohort, those <40 had even greater MSH2 loss and less COX2 expression. In all patients <50, MSI-H tumors were more likely to lose p27 expression (p<0.0015). Loss of p27 was associated with female gender, higher tumor grade and lymph node positivity. Increased COX2 staining was associated with lower tumor grade and stage, smaller size and with less invasion, lymph node positivity and mucinous/ signet ring differentiation. Patients <40 had more poorly differentiated and left-sided/rectal tumors, more retrieved lymph nodes, deeper invasion, more mucinous and signet ring differentiation, Crohns-like inflammation and AJCC stage II and III tumors (range p<0.0001 to 0.03). Other morphologic factors were not significantly different.
Conclusions: Our data show that CRC in young patients has a higher incidence of MSH2 loss and lower COX2 expression, while loss of MLH1 and p27 is similar to that seen in the older population. Increased COX2 staining was associated with favorable morphologic features, while loss of p27 was associated with unfavorable ones. These data suggest that COX2 may play a different role in young patients with CRC, and that COX2 inhibitors may be less relevant as a prophylactic or therapeutic modality in these patients.
Category: Gastrointestinal

Monday, March 22, 2010 9:15 AM

Platform Session: Section E, Monday Morning