Table 1.

Loss of SMAD4 protein expression in early-onset colorectal cancers.

	Total	SMAD4 staining (%)
		Positive	Negative
Tumour site
colonic tumours	66	55 (83)	11 (17)
Right colon	35	30 (86)	5 (14)
Splenic flexure	2	1 (50)	1 (50)
Left colon	29	24 (83)	5 (17)
Rectal tumours	41	26 (63)	15 (36)*
Site unknown	2	1	1
Total tumours	109	82 (75)	27 (25)
TGFβR11
Frameshift mutation	21	18 (86)	3 (14)
No mutations	82	61 (74)	21 (26)
No data	6	3	3
Total	109	82	27
SMAD4 gene copy number
Loss of copy number	27	14 (51)	13 (48)
No change	21	9 (42)	12 (544)
Gain of copy number	4	4 (100)	0
No data	4	2 (50)	2 (50)
Total	56	29	27
MSI
MSI-High	17	14 (82)*	3 (18)‡
MSI-Low	18	13 (72)†	5 (28)
MSS	70	52 (74)	18 (26)
No data	4
Total	109	82	27

Loss of SMAD4 protein expression was more common in tumours diagnosed in the rectum than in the colon (P = 0.04).

^*Ten patients with early-onset colorectal cancer had germ-line mutations in MMR genes (8 in MLH1 and 2 in MSH2).

^†Four patients with early-onset colorectal cancer had germ-line mutations in MSH6.

^‡All three patients with early-onset colorectal cancer had germ-line mutations in MMR genes (1 in MLH1 and 2 in MSH2).