Identification of patients at-risk for Lynch syndrome in a hospital-based colorectal surgery clinic

Table 1 Clinical criteria for Lynch syndrome

Name	Criteria	Sensitivity1	Specificity1
Amsterdam	Amsterdam criteria I	61.0%	67.0%
	Three or more relatives with colorectal cancer, one of whom is a first-degree relative of the other two, FAP should be excluded
	Colorectal cancer involving at least two generations
	One or more colorectal cancer cases diagnosed before the age of 50
	Amsterdam criteria II	78.0%	61.0%
	Three or more relatives with histologically verified LS-associated cancer (colorectal cancer, cancer of the endometrium, small bowel, ureter, or renal pelvis), 1 of whom is a first-degree relative of the other 2; FAP should be excluded
	Colorectal cancer involving at least two generations
	One or more cancer cases diagnosed before the age of 50
Revised bethesda	At least one of the following features	90.9%	77.1%
	Bethesda 1: Colorectal cancer diagnosed in a patient under the age of 50
	Bethesda 2: Presence of synchronous or metachronous colorectal cancer, or other LS-associated tumors2, regardless of age
	Bethesda 3: Colorectal cancer with the MSI-H histology3 under the age of 60
	Bethesda 4: Colorectal cancer in one or more first-degree relatives with an LS-related tumor, with one of the cancers under the age of 50
	Bethesda 5: Colorectal cancer in two or more first- or second-degree relatives with LS-related tumors, regardless of age

¹Data on sensitivity and specificity of Amsterdam criteria from Syngal et al[14] and Revised Bethesda from Piñol et al[46];

²Lynch syndrome (LS)-associated tumors include colorectal, endometrial, stomach, ovarian, pancreas, ureter and renal pelvis, biliary tract, brain tumors, sebaceous gland adenomas and keratoacanthomas in Muir-Torre syndrome, and carcinoma of the small bowel;

³Presence of tumor infiltrating lymphocytes, Crohn’s-like lymphocytic reaction, mucinous/signet-ring differentiation, or medullary growth pattern. FAP: Familial adenomatous polyposis; MSI-H: Microsatellite instability-high.

Table 2 Sample description by criteria for Lynch syndrome (n = 212)

Lynch syndrome criteria	n (%)
Amsterdam	22 (10.4)
Amsterdam I	16 (7.6)
Amsterdam II	6 (2.8)
Bethesda (at least 1 of the 5 criteria)	100 (47.2)
Bethesda (2 or more of the criteria)	41 (19.3)
Bethesda by criteria
Bethesda 1	45 (21.2)
Bethesda 2	17 (8.0)
Bethesda 3	27 (12.7)
Bethesda 4	23 (10.8)
Bethesda 5	36 (17.0)

Table 3 Features of the 223 colorectal tumors in the 212 probands¹

Feature	n (%)
Tumor site
Ascending colon	22 (9.9)
Transverse colon	12 (5.4)
Descending colon	11 (5.0)
Rectosigmoid	158 (71.1)
Other (cecum, unspecified site)	19 (8.6)
Total	222 (100.0)
Missing data	1
Differentiation
Well differentiated	20 (10.0)
Moderately differentiated	157 (78.1)
Poorly differentiated	24 (11.9)
Total	201 (100.0)
Missing data	22
Mucinous feature	15 (6.7)
Total	223 (100.0)
Missing data	0
MSI-high phenotype2	42 (21.3)
Total	197 (100.0)
Missing data	26
Dukes stage (n = 195)
A	6 (3.1)
B	76 (39.0)
C	87 (44.6)
D	26 (13.3)
Total	195 (100.0)
Missing data	28

¹Cases with missing data were excluded from the analysis;

²Cases included all patients with microsatellite instability-high phenotype, independent of age.

Table 4 Comparison of different features among patients with and without the microsatellite instability-high phenotype (n = 197¹) n (%)

Features	MSI-high phenotype (n = 42)	Non MSI-high phenotype (n = 155)	P
Age at diagnosis < 50 yr	18 (42.9)	29 (18.7)	0.001
Family history of colorectal cancer	15 (35.7)	45 (29.0)	0.404
Presence of Revised Bethesda criteria[16]	42 (100)	56 (36.1)	< 0.001
Presence of Amsterdam II criteria	6 (14.3)	15 (9.7)	0.391
Second primary tumors	3 (7.1)	8 (5.2)	0.620
Early stage at diagnosis	11 (26.2)	64 (41.3)	0.079

¹15 patients were excluded due to missing data on tumor histology. MSI: Microsatellite instability.