Tumor budding predicts response to anti-EGFR therapies in metastatic colorectal cancer patients

Table 1 Characteristics of metastatic colorectal cancer patients treated with anti-epidermal growth factor receptor therapy (n = 43) n (%)

Clinico-pathological feature	Frequency
Age (yr), median (range)	64 (26-82)
Gender
Male	26 (60.5)
Female	17 (39.5)
Response
Progressive disease	19 (44.2)
Partial response	13 (30.2)
Stable disease	11 (25.6)
EGFR
No Amplification/gene copy number gain	4 (10.5)
Amplification/gene copy number gain	34 (89.5)
K-RAS
Wild-type	32 (74.4)
Mutation	11 (25.6)
B-RAF
Wild-type	38 (88.4)
Mutation	5 (11.6)
PIK3CA
Wild-type	41 (95.4)
Mutation	2 (4.7)
PTEN
Negative	12 (27.9)
Positive	31 (72.1)
Overall survival time (mo), median (range)	37.3 (3.6-180)
Progression-free survival (mo), median (range)	16.0 (1-171)
Number of tumor buds, median (range)	9.0 (1-44)
Tumor budding
High	11 (25.6)
Low	32 (74.4)

EGFR: Epidermal growth factor receptor.

Table 2 Predictive ability of each feature for partial response

Feature	Total No. of patients	No. of correctly predicted PR	No. of correctly predicted PD + SD	No. of PD + SD predicted as PR	No. of PR predicted as PD + SD	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	Accuracy (%)	P-value
Budding ( ≤ 15 cells)	43	13	11	19	0	100	40.6	37	100	68.3	0.011
EGFR (no AMP/CNG)	38	10	4	24	0	100	29.4	14	100	57.1	0.556
K-RAS (wild-type)	43	13	11	19	0	100	40.6	37	100	68.3	0.011
B-RAF (wild-type)	43	13	5	25	0	100	34.2	17	100	58.3	0.301
PIK3CA (wild-type)	43	13	2	28	0	100	31.7	7	100	53.3	1.0
PTEN (positive)	43	12	11	19	1	91.7	38.7	37	92.3	64.5	0.07

PD: Progressive disease; SD: Stable disease; PR: Partial response; EGFR: Epidermal growth factor receptor; PPV: Positive predictive value; NPV: Negative predictive value; AMP/CNG: Amplification or copy number gain.

Table 3 Tumor budding and K-RAS followed by PTEN, epidermal growth factor receptor, B-RAF and PIK3CA stratified by response group

Response	K-RAS	Tumor budding	PTEN	EGFR (AMP/CNG)	B-RAF	PIK3CA
NR	WT	Low	NEG	Yes	WT	WT
NR	WT	Low	NEG	Yes	WT	WT
NR	WT	Low	NEG	Yes	WT	WT
NR	WT	Low	NEG	Yes	WT	WT
NR	WT	Low	NEG	Yes	MUT	WT
NR	WT	Low	POS	No	WT	WT
NR	WT	Low	POS	No	WT	WT
NR	WT	Low	POS	Yes	WT	WT
NR	WT	Low	POS	Yes	WT	WT
NR	WT	Low	POS	Yes	WT	WT
NR	WT	Low	POS	NE	MUT	WT
NR	WT	Low	POS	No	MUT	MUT
NR1	WT	High	NEG	No	WT	WT
NR1	WT	High	NEG	Yes	WT	WT
NR1	WT	High	NEG	Yes	MUT	MUT
NR1	WT	High	POS	Yes	WT	WT
NR1	WT	High	POS	Yes	WT	WT
NR1	WT	High	POS	Yes	WT	WT
NR1	WT	High	POS	Yes	MUT	WT
NR1	MUT	Low	NEG	Yes	WT	WT
NR1	MUT	Low	POS	Yes	WT	WT
NR1	MUT	Low	POS	Yes	WT	WT
NR1	MUT	Low	POS	Yes	WT	WT
NR1	MUT	Low	POS	Yes	WT	WT
NR1	MUT	Low	POS	Yes	WT	WT
NR1	MUT	Low	POS	Yes	WT	WT
NR1	MUT	High	NEG	Yes	WT	WT
NR1	MUT	High	NEG	Yes	WT	WT
NR1	MUT	High	POS	No	WT	WT
NR1	MUT	High	POS	Yes	WT	WT
PR1	WT	Low	NEG	NE	WT	WT
PR1	WT	Low	POS	NE	WT	WT
PR1	WT	Low	POS	NE	WT	WT
PR1	WT	Low	POS	Yes	WT	WT
PR1	WT	Low	POS	Yes	WT	WT
PR1	WT	Low	POS	Yes	WT	WT
PR1	WT	Low	POS	Yes	WT	WT
PR1	WT	Low	POS	Yes	WT	WT
PR1	WT	Low	POS	Yes	WT	WT
PR1	WT	Low	POS	Yes	WT	WT
PR1	WT	Low	POS	Yes	WT	WT
PR1	WT	Low	POS	Yes	WT	WT
PR1	WT	Low	POS	Yes	WT	WT

¹Cases which were correctly predicted using K-RAS and tumor budding. EGFR: Epidermal growth factor receptor; AMP/CNG: Amplification or copy number gain; MUT: Mutation; NE: Not evaluable; NEG: Negative; NR: Non response; POS: Positive; PR: Partial response; WT: Wld-type.