Table 2.
Patient No | Family No | Analysed for MLH1 or MSH2 mutation | Mutation detected | Multiple HNPCC related cancers in at least one family member | No of right sided CRC in the family | MSI (our selected markers) | MSI (NCI reference panel) | Proband age at time of CRC diagnosis (y) | Categorised as HNPCC* |
Category 1—Amsterdam criteria I | |||||||||
1 | 1 | Yes | MLH1 | Yes | 5 | MSI-H | MSI-H | 39, 52 | + |
2 | 1 | Yes | MLH1 | Yes | 5 | MSI-H | MSI-H | 28 | + |
3 | 2 | Yes | MLH1 | Yes | 3 | MSI-H | MSI-H | 49 | + |
4 | 3 | Yes | MSH2 | Yes | 5 | MSI-H | MSI-H | 35, 72, 75 | + |
5 | 4 | Yes | MSH2 | Yes | 2 | MSI-H | MSI-L | 65 + En55 | + |
6 | 5 | Yes | No | No | 0 | † | na | 38 | + |
7 | 6 | Yes | No | No | 0 | MSI-H | MS-S | 60 | + |
8 | 7 | Yes | No | No | 0 | MSI-H | MS-S | 42 | + |
9 | 8 | Yes | No | No | 1 | MS-S | MS-S | 57 | + |
10 | 9 | Yes | No | No | 0 | MS-S | MS-S | 44 | + |
11 | 10 | Yes | No | No | 1 | MS-S | MSI-H | 45 | + |
Category 2—Amsterdam criteria II | |||||||||
12 | 11 | Yes | MLH1 | Yes | 3 | MSI-H | 38, 54 | + | |
13 | 12 | Yes | MSH2 | Yes | 1 | MSI-H | 43 | + | |
14 | 13 | Yes | No | No | 0 | MSI-L | 70 | + | |
15 | 14 | Yes | No | No | 0 | MS-S | 31 | + | |
16 | 4 | Yes | MSH2 | Yes | 2 | MSI-H | 36, 58 | + | |
17 | 15 | Yes | No | No | 0 | MS-S | 49 | + | |
Category 3—Amsterdam criteria I or II on extended pedigree | |||||||||
18 | 16 | Yes | No | Yes | 2 | MS-S | 46, 46, 46 | + | |
Category 4—Amsterdam criteria including other HNPCC related cancer | |||||||||
19 | 17 | Yes | No | No | 2 | MS-S | 76 | ||
20 | 18 | Yes | No | No | 0 | MS-S | 82 | ||
21 | 19 | Yes | No | No | 0 | MS-S | 47 | ||
22 | 20 | Yes | No | No | 1 | MSI-H | 70 | ||
23 | 21 | Yes | No | No | 0 | † | 81 | ||
24 | 22 | Yes | No | No | 0 | † | 34 | ||
25 | 23 | Yes | No | No | 1 | † | 72 | ||
26 | 24 | Yes | No | No | 0 | MS-S | 75 | ||
27 | 25 | Yes | No | Yes | 0 | MS-S | 39, 62 | ||
28 | 26 | Yes | No | Yes | 0 | MSI-L | 49,52 | ||
29 | 26 | No | na | Yes | 0 | MS-S | 81 | ||
30 | 27 | No | na | Yes | 0 | MS-S | 73 | ||
Category 5—Amsterdam criteria I (youngest family member with CRC 50–55 y at the time of diagnosis) | |||||||||
31 | 28 | Yes | No | Yes | 0 | MS-S | 52, 52 | ||
32 | 29 | Yes | No | No | 0 | MS-S | 52 | ||
33 | 30 | Yes | No | No | 0 | MS-S | 56 | ||
34 | 31 | Yes | No | No | 1 | MS-S | 81 | ||
35 | 32 | Yes | No | No | 1 | † | 81 | ||
36 | 33 | No | na | No | 0 | MS-S | 58 | ||
Category 6—proband at age 40 y or younger with at least one CRC among family members | |||||||||
37 | 34 | Yes | MSH2 | No | 0 | MSI-H | 26 | + | |
38 | 35 | Yes | No | No | 0 | † | 34 | ||
39 | 36 | Yes | No | No | 0 | MS-S | 19 | ||
40 | 37 | Yes | No | No | 0 | MS-S | 40 | ||
41 | 38 | Yes | No | No | 0 | MS-S | 34 | ||
Category 7—both proband and one first degree relative with CRC <55 y | |||||||||
42 | 39 | Yes | MSH2 | No | 1 | MSI-H | 52 | + | |
43 | 40 | Yes | No | No | 1 | MS-S | 53 | ||
44 | 41 | Yes | No | No | 0 | MS-S | 49 | ||
45 | 42 | No | na | No | 1 | MS-S | 49 |
†Amplification of tumour DNA not possible.
*Families from categories 1–3 meet the International Collaborative Group for HNPCC clinical criteria for HNPCC, and we categorised these families as HNPCC. Families from categories 4–7 were categorised as HNPCC only if hMLH1/hMSH2 mutations were detected.
En, endometrial cancer; na, not analysed; MSI, microsatellite instability; MSI-H, high microsatellite instability; MSI-L, low microsatellite instability; MS-S, stable microsatellites; CRC, colorectal cancer.