World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website http://www.wjon.org

Original Article

Volume 4, Number 4-5, October 2013, pages 179-187

Clinical-Pathological Correlation of KRAS Mutation Status in Metastatic Colorectal Adenocarcinoma

Figure 1. Kaplan-Meier Overall Survival Curves according to KRAS gene status (mutated and wild-type), P-value = 0.407. Legend: K-RAS mutated: 1; K-RAS wild-type: 2.

Figure 2. Kaplan-Meier Overall Survival Curves of patients with K-RAS mutated according to mutation in codons 12 and 13, P-value = 0.651. Legend: K-RAS mutated codon 12: 1; K-RAS mutated codon 13: 2.

**Table 1.** Distribution of K-RAS Mutation Status and Clinical-Pathological Tumor Features in Colorectal Cancer Patients
Clinical-pathological features	Total (n = 65)	K-RAS wild-type (n = 33)	K-RAS mutated (n = 32)	P-value
ECOG: Eastern Cooperative Oncology Group; LNR: lymph node ratio.
Gender	0.195
Male	28	12	16
Female	37	21	16
Age	0.046
> 65 years	44	30	14
< 65 years	21	3	18
ECOG	0.495
0	38	17	21
1	25	15	10
2	2	1	1
Histological type				0.256
Adenocarcinoma	50	27	23
Mucinous	15	6	9
Cell differentiation	0.221
well	49	27	22
intermediate	16	6	10
LNR > 0.16	(60)			0.371
Yes	34	17	17
No	26	11	15
Lung metastasis				0.531
Yes	34	16	18
No	31	17	14
Liver metastasis				0.663
Yes	43	21	22
No	22	12	10
Synchronous metastasis	0.051
Yes	35	14	21
No	30	19	11
Primary tumor site				0.914
Colon	28	14	14
Rectum	37	19	18
Obstructive and/or perforated acute abdomen	0.273
Yes	11	7	4
No	54	26	28
Staging				0.074
II	13	10	3
III	17	9	8
IV	35	14	21
Recurrence				0.067
Yes	56	31	25
No	9	2	7

Table 1. Distribution of K-RAS Mutation Status and Clinical-Pathological Tumor Features in Colorectal Cancer Patients

Clinical-pathological features

Total (n = 65)

K-RAS wild-type (n = 33)

K-RAS mutated (n = 32)

P-value

ECOG: Eastern Cooperative Oncology Group; LNR: lymph node ratio.

Gender

0.195

Male

Female

Age

0.046

> 65 years

< 65 years

ECOG

0.495

Histological type

0.256

Adenocarcinoma

Mucinous

Cell differentiation

0.221

well

intermediate

LNR > 0.16

(60)

0.371

Yes

Lung metastasis

0.531

Yes

Liver metastasis

0.663

Yes

Synchronous metastasis

0.051

Yes

Primary tumor site

0.914

Colon

Rectum

Obstructive and/or perforated acute abdomen

0.273

Yes

Staging

0.074

III

Recurrence

0.067

Yes

**Table 2.** Distribution of K-RAS Mutation Types in Colorectal Cancer Patients, Point Mutations and Amino Acids Exchanged
Codon	Missense mutation	Amino acid Wild-type	Amino acid mutated	n = 32 (%)
n: number of patients; G: nucleotide glycine; A: nucleotide alanine; T: nucleotide thymine; C: nucleotide cytosine; Gly: nucleotide glycine; Asp: nucleotide aspartate; Val: nucleotide valine; Ala: nucleotide alanine; Ser: nucleotide serine; Cys: nucleotide cisteine.
12 (n = 24)	G-A	GGT (Gly)	GAT (Asp)	11 (34.37%)
	G-T	GGT (Gly)	GTT (Val)	6 (18.75%)
	G-T	GGT (Gly)	TGT (Cys)	4 (12.5%)
	G-A	GGT (Gly)	AGT (Ser)	2 (6.25%)
	G-C	GGT (Gly)	GCT (Ala)	1 (3.125%)
13 (n = 8)	G-A	GGC (Gly)	GAC (Asp)	7 (21.87%)
	G-T	GGC (Gly)	GTT (Val)	1 (3.125%)

Table 2. Distribution of K-RAS Mutation Types in Colorectal Cancer Patients, Point Mutations and Amino Acids Exchanged

Codon

Missense mutation

Amino acid Wild-type

Amino acid mutated

n = 32 (%)

n: number of patients; G: nucleotide glycine; A: nucleotide alanine; T: nucleotide thymine; C: nucleotide cytosine; Gly: nucleotide glycine; Asp: nucleotide aspartate; Val: nucleotide valine; Ala: nucleotide alanine; Ser: nucleotide serine; Cys: nucleotide cisteine.

12 (n = 24)

G-A

GGT (Gly)

GAT (Asp)

11 (34.37%)

G-T

GGT (Gly)

GTT (Val)

6 (18.75%)

G-T

GGT (Gly)

TGT (Cys)

4 (12.5%)

G-A

GGT (Gly)

AGT (Ser)

2 (6.25%)

G-C

GGT (Gly)

GCT (Ala)

1 (3.125%)

13 (n = 8)

G-A

GGC (Gly)

GAC (Asp)

7 (21.87%)

G-T

GGC (Gly)

GTT (Val)

1 (3.125%)

**Table 3.** Binary Logistic Regression Analysis and Distribution of the Probabilities of Occurrence of Liver and Lung Metastases According to Primary Site and Tumor KRAS Mutation Status
		Kras wild-type	Kras mutated	P-value
P: probability.
Liver metastasis	colon	P: 0.766581	P: 0.804848	0.160
	rectum	P: 0.540414	P: 0.596230
Lung metastasis	colon	P: 0.424453	P: 0.504118	0.579
	rectum	P: 0.529350	P: 0.607908

Table 3. Binary Logistic Regression Analysis and Distribution of the Probabilities of Occurrence of Liver and Lung Metastases According to Primary Site and Tumor KRAS Mutation Status

Kras wild-type

Kras mutated

P-value

P: probability.

Liver metastasis

colon

P: 0.766581

P: 0.804848

0.160

rectum

P: 0.540414

P: 0.596230

Lung metastasis

colon

P: 0.424453

P: 0.504118

0.579

rectum

P: 0.529350

P: 0.607908

**Table 4.** Multivariate Analysis of Clinical-Pathological Features Associated With Prognostic Value in Colorectal Cancer Patients
Characteristics	Relative Risk	CI (Confidence interval) 95%	P-value
K-RAS mutation	-1.76	-0.9537 - 0.0501	0.078
Cell differentiation,	-0.79	-0.8236 - 0.3492	0.428
Gender	-0.74	-0.6267 - 0.2829	0.459
Age	0.47	-0.0118 - 0.0191	0.642
Primary tumor site	1.16	-0.1708 - 0.6679	0.245
Lymph node involvement	-1.62	-0.8142 - 0.0763	0.104
Liver metastasis	2.65	0.2427 - 1.6257	0.008
Lung metastasis	-1.56	0.7462 - 0.0859	0.120
Synchronous metastasis	2.92	0.2961 - 1.4998	0.003
Histological type	-0.70	-0.6845 - 0.3248	0.485

Table 4. Multivariate Analysis of Clinical-Pathological Features Associated With Prognostic Value in Colorectal Cancer Patients

Characteristics

Relative Risk

CI (Confidence interval) 95%

P-value

K-RAS mutation

-1.76

-0.9537 - 0.0501

0.078

Cell differentiation,

-0.79

-0.8236 - 0.3492

0.428

Gender

-0.74

-0.6267 - 0.2829

0.459

Age

0.47

-0.0118 - 0.0191

0.642

Primary tumor site

1.16

-0.1708 - 0.6679

0.245

Lymph node involvement

-1.62

-0.8142 - 0.0763

0.104

Liver metastasis

2.65

0.2427 - 1.6257

0.008

Lung metastasis

-1.56

0.7462 - 0.0859

0.120

Synchronous metastasis

2.92

0.2961 - 1.4998

0.003

Histological type

-0.70

-0.6845 - 0.3248

0.485