Cost-effective screening using a two-antibody panel for detecting mismatch repair deficiency in sporadic colorectal cancer

Table 1 Clinicopathological characteristics according to microsatellite instability (n = 3486)

Characteristics		MSS	MSI-H	P value
n (%)		3293 (94.5)	193 (5.5)
Sex	Male	1958 (59.5)	106 (54.9)	0.213
	Female	1335 (40.5)	87 (45.1)
Age (mean ± SD, yr)		62.37 ± 11.68	59.84 ± 15.36	< 0.001
	≤ 50	513 (15.6)	56 (29.0)
	> 50	2780 (84.4)	137 (71.0)
CEA (median ± IQR)		2.4 ± 1.4-5.3	2.1 ± 1.1-5.4	0.630
	< 6 ng/mL	2515 (77.1)	142 (75.5)
	≥ 6 ng/mL	749 (22.9)	46 (24.5)
Location	Right colon	767 (23.3)	145 (75.1)	< 0.001
	Left colon	989 (30.0)	31 (16.1)
	Rectum	1537 (46.7)	17 (8.8)
pT	T0 /T1/T2	828 (25.1)	47 (24.4)	0.805
	T3/T4	2465 (74.9)	146 (75.6)
pN	N0	1765 (53.6)	142 (73.6)	< 0.001
	N1/N2	1526 (46.4)	51 (26.4)
pM	M0	2742 (83.3)	185 (95.9)	< 0.001
	M1	551 (16.7)	8 (4.1)
Differentiation grade	WD/MD	3022 (95.2)	138 (81.2)	< 0.001
	PD/MA	154 (4.8)	32 (18.8)
LVI	No	1782 (54.2)	133 (69.3)	< 0.001
	Yes	1504 (45.8)	59 (30.7)
PNI	No	2299 (70.2)	169 (88.5)	< 0.001
	Yes	977 (29.8)	22 (11.5)

MSS: Microsatellite stable; MSI-H: High-frequency microsatellite instability; SD: Standard deviation; CEA: Carcinoembryonic antigen; IQR: Interquartile range; pT: Pathological tumor stage; pN: Pathological nodal stage; pM: Pathological metastatic stage; WD: Well-differentiated adenocarcinomas; MD: Moderately-differentiated adenocarcinomas; PD: Poorly-differentiated adenocarcinomas; MA: Mucinous adenocarcinomas; LVI: Lymphovascular invasion; PNI: Perineural invasion.

Table 2 Immunohistochemistry patterns (n = 3486)

Expression patterns	n (%)
Retained expression of 4 proteins	3285 (94.2)
Loss of at least 1 protein	201 (5.8)
Loss of PMS2	136 (3.9)
Loss of MLH1	133 (3.8)
Loss of MSH6	58 (1.7)
Loss of MSH2	49 (1.4)
Concurrent loss of MLH1 and PMS2	126 (3.6)
Loss of PMS2 alone	10 (0.3)
Loss of MLH1 alone	7 (0.2)
Concurrent loss of MSH2 and MSH6	43 (1.2)
Loss of MSH6 alone	15 (0.4)
Loss of MSH2 alone	6 (0.2)

Table 3 Validity of 4- and 2-antibody panels in immunohistochemistry based on a microsatellite instability test

	4-antibody IHC	2-antibody IHC
		PMS2/ MSH6	MLH1/MSH2
Sensitivity (95%CI)	97.4%(93.7-99.0)	92.2%(87.3-95.4)	87.6%(81.9-91.7)
Specificity (95%CI)	99.6%(99.3-99.8)	99.6%(99.3-99.8)	99.7%(99.5-99.9)
κ	0.952	0.923	0.906

CI: Confidence interval; κ: Cohen's kappa statistic (value of kappa ≥ 0.90, almost perfect agreement)[10]. IHC: Immunohistochemistry.

Table 4 Discrepancy between the results of microsatellite instability test and immunohistochemistry

MSI status	IHC							(n = 32)
	MLH1	MSH2	PMS2	MSH6	Causes of discrepancy			Overall
					PF	LE	Unknown
MSI-H	+	+	+	+	0	0	5	5
MSS	Loss	+	Loss	+	6	11	4	11
	+	Loss	+	Loss	0	11	5	6
	+	+	Loss	+	2	1	1	4
	+	+	+	Loss	0	0	3	3
	Loss	+	+	+	2	0		2
	Loss	Loss	+	Loss	1	0		1

MSI-H: High-frequency microsatellite instability; MSS: Microsatellite stable; “+”: Retained expression of protein; Loss: Loss of MMR protein expression; PF: Poor fixation; LE: Low expression (i.e., ¹radiotherapy).