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Purpose: In an effort to capture patients in our surgical practice considered high-risk for Lynch Syndrome because of young age, reflex microsatellite instability (MSI) testing was initiated on all colorectal cancers resected from young patients not tested preoperatively. This protocol provides a unique opportunity to retrospectively compare surgical management in high-risk patients who were tested either preoperatively or postoperatively for MSI. We aimed to determine if MSI status altered surgical management when the result was known preoperatively.Methods: Starting in 2003, the pathologist handling the resection specimens ordered MSI testing on all newly diagnosed young-onset CRC (≤ 50 years old) cases not tested prior to surgical resection. Patients with inflammatory bowel disease and polyposis syndromes were excluded. We categorized tumors as microsatellite stable (MSS), which included MSI-low tumors, and MSI-high (MSI-H), with or without germ-line mutation. Clinicopathologic features and surgical procedures performed were reviewed.Results: Between 2003 and 2008, 210 newly diagnosed young-onset CRC patients undergoing surgery had MSI testing. Results of testing were available preoperatively in 103 patients and postoperatively, secondary to the reflex protocol, in 107 patients. MSI-H tumors were found in 16/103 (16%) in the preoperatively tested group and 12/107 (11%) in the postoperatively tested group. Comparison of clinicopathologic features and surgical intervention between groups are listed in Table 1. MSI-H status known preoperatively significantly influenced surgical recommendations of total colectomy compared to patients where status was not known until after surgery (94% vs. 8%, p<0.0001). Hysterectomy was performed in 8/10 women when preoperative MSI-H status was known (one had metastatic disease, one was of childbearing age). There was only one female patient in the postoperative group and she did not undergo hysterectomy. Germ-line mutations were positive in 10/16 (63%) MSI-H patients tested. Two patients had germ-line testing available preoperatively. Conclusion: MSI-H status was found in 13% of young-onset colorectal cancer patients operated at our institution, and 63% of those tested, had germ-line mutations. Knowledge of MSI status preoperatively significantly influenced surgical management with an increase in total colectomy and hysterectomy compared to patients whose MSI-H status was discovered postoperatively. The absence of germ-line testing in MSI-H patients did not appear to influence surgical decision making.
Table 1: Clinicopathologic features and surgical intervention of MSI-H patients in preoperatively tested and postoperatively tested groups

Characteristics	MSI-H PreopN=16	MSI-H PostopN=12	p-value
Age, years (mean)	39.3 ± 8.2	41 ± 10	0.42
BMI, kg/m2	28.7 ± 9.9	26.2 ± 5.8	0.85
Female	10 (62.5%)	1 (8.3%)	0.005
Location, Right colon	9 (56.3 %) †	6 (50 %)	0.52
Transverse colon	1 (6.3%)	0 (0%)	0.57
Left colon	1 (6.3%)	1 (8.3 %)	0.68
Sigmoid colon	0 (0%)	1 (8.3 %)	0.43
Rectum	6 (37.5%) †	4 (33.3%)	0.57
Stage I	5 (31.3%)	3 (25%)	0.53
Stage II	6 (37.5%)	4 (33.3%)	0.57
Stage III	3 (18.8%)	2 (16.7%)	0.64
Stage IV	2 (12.5%)	3 (25%)	0.36
Family history: 1° relative CRC	7 (43.8%)	2 (16.7%)	0.11
Any family history CRC	13 (81.3%)	5 (41.7%)	0.04
Total colectomy recommended	15 (94%)	1 (8.3%)	<0.0001
Total colectomy performed	11 (68.8%)	1 (8.3%)	0.002
Hysterectomy (females only)	8 (80%)	0 (0%)	0.27
Genetic testing performed	12 (75%)	4 (33.3%)	0.09
Positive germline mutation	9 (56.3%)	1 (8.3%)	0.01