Article Figures & Data
Figures
- Fig. 1.
Representative PCR-RFLP patterns of different EGFR codon 497 status examined by patients' blood samples. Genomic DNA obtained from patients' WBC was subjected to PCR amplification using 5′-TGCTGTGACCCACTCTGTCT-3′ and 5′-CCAGAAGGTTGCACTTGTCC-3′ as forward and reverse primers, respectively. PCR products after being digested by BstN1 were separated by agarose gel electrophoresis.
- Fig. 2.
Representative immunohistochemical staining patterns of the phosphorylated EGFR as well as activated c-Myc in patients' tumor tissues. Immunohistochemical staining of 36 colorectal carcinoma patients' tumor tissues was done using anti–phosphorylated EGFR (pEGFR; A) and anti-c-Myc (B) antibodies, respectively. Left, positive staining; right, negative staining. Correlations between EGFR phosphorylation as well as c-Myc activation and EGFR R497K polymorphism were analyzed by χ2 test.
- Fig. 3.
The EGFR mRNA levels are not affected by the R497K polymorphism in its gene. PCR-RFLP analysis of 15 colorectal carcinoma patients was done as described in Fig. 1, whereas reverse transcription-PCR (RT-PCR) was carried out using total RNAs isolated from the same blood samples with EGFR-specific and glyceraldehyde-3-phosphate dehydrogenase (GAPDH)–specific primer sets, respectively.
- Fig. 4.
Stage II/III colorectal carcinoma patients with the R497K polymorphism of EGFR are associated with a longer disease-free as well as overall survival. A, disease-free survival curves of 100 stage II/III colorectal carcinoma patients with EGFR 497R (•) or 497K (○) were plotted by Kaplan-Meier method (P < 0.001, log-rank test). B, similar method was used to plot disease-free survival curves of patients with wild (•), homozygous (△), or heterozygous (○) codon 497 genotypes (P < 0.001, log-rank test). C, overall survival curves of patients with EGFR 497R (•) or 497K (○) were plotted by similar method (P < 0.01, log-rank test).
- Fig. 5.
Metastatic colorectal carcinoma patients with the R497K polymorphism of EGFR are associated with a longer survival. Survival curves of 109 metastatic colorectal carcinoma patients with EGFR 497R (homozygote; •) and 497K (homozygote or heterozygote; ○) in their blood samples were plotted by Kaplan-Meier method (P < 0.001, log-rank test).
Tables
- Table 1.
Clinicopathologic influences of the EGFR codon 497 polymorphism in stage II/III colorectal cancer patients receiving curative surgery
Characteristics G/G (wild-type), n (%) G/A or A/A, n (%) P All patients 27 (100) 73 (100) Age (y) <50 13 (48.1) 39 (53.4) 0.81 ≥50 14 (51.9) 34 (46.6) Gender Male 17 (63.0) 50 (68.5) 0.78 Female 10 (37.0) 23 (31.5) Performance status 0 18 (66.7) 52 (71.2) 0.84 1, 2 9 (33.3) 21 (28.8) Primary tumor Colon 16 (59.3) 46 (63.0) 0.91 Rectum 11 (40.7) 27 (37.0) Histologic differentiation Well/moderate 20 (74.1) 58 (79.5) 0.76 Poorly/unknown 7 (25.9) 15 (20.5) Invasive extent T1-T2 9 (33.3) 47 (64.4) 0.01 T3-T4 18 (66.7) 26 (35.6) Lymph node status N0 11 (40.7) 51 (69.9) 0.02 N1-N3 16 (59.3) 22 (30.1) Subsequent distant metastasis No 6 (22.2) 63 (86.3) <0.01 Yes 21 (77.8) 10 (13.7) Preoperative CEA level (ng/mL) ≤6 13 (48.1) 42 (57.5) 0.54 >6 14 (51.9) 31 (42.5) NOTE: According to international TNM staging system for colorectal carcinoma.
Abbreviations: G, guanine; A, adenine.
- Table 2.
The correlation of EGFR codon 497 polymorphism between patients' WBCs and colorectal tumor tissues (n = 36)
WBC Primary colorectal tumor tissues G/G (Arg/Arg) G/A (Arg/Lys) A/A (Lys/Lys) G/G (Arg/Arg) 9 0 0 G/A (Arg/Lys) 0 17 0 A/A (Lys/Lys) 0 0 10 - Table 3.
Analysis of factors that may affect the survival of patients with stage II/III colorectal carcinoma (n = 100)
Characteristics Univariate, P Multivariate, P Age (y) <50 vs ≥50 0.77 0.82 Gender Male vs female 0.95 0.70 Performance status 0 vs 1, 2 0.12 0.08 Primary tumor Colon vs rectum 0.56 0.91 Histologic differentiation Well-moderate vs poorly 0.22 0.49 Invasive extent T1-T2 vs T3-T4 0.03 0.05 Nodal status Negative vs positive 0.04 0.03 Subsequent distant metastasis No vs yes 0.01 <0.01 Preoperative CEA level (ng/mL) ≤6 vs >6 0.48 0.65 EGFR codon 497 polymorphism G/G (wild-type) vs G/A or A/A 0.02 0.03 NOTE: According to international TNM staging system for colorectal carcinoma.
- Table 4.
The response to 5-FU plus oxaliplatin treatment in metastatic colorectal cancer patients with different EGFR codon 497 status
Response G/G (wild-type), n (%) G/A or A/A, n (%) P* All patients enrolled 38 (100) 71 (100) OR (CR + PR) 13 (34.2) 44 (62.0) 0.02 CR 2 (5.3) 6 (8.5) PR 11 (28.9) 38 (53.5) SD 18 (47.4) 19 (26.8) PD 7 (18.4) 8 (11.3) Abbreviations: OR, overall response; CR, complete remission; PR, partial remission; SD, stable disease; PD, progressive disease.
↵* Comparison of overall response rate between patients with different EGFR codon 497 polymorphisms.
- Table 5.
Analysis of factors that may affect the survival of patients with metastatic colorectal carcinoma (n = 109)
Characteristics Univariate, P Multivariate, P Age (y) <50 vs ≥50 0.64 0.72 Gender Male vs female 0.76 0.88 Performance status 0 vs 1, 2 0.32 0.04 Primary tumor Colon vs rectum 0.81 0.84 Histologic differentiation Well-moderate vs poorly 0.53 0.68 Invasive extent T1-T2 vs T3-T4 0.08 0.03 Known vs unknown 0.56 0.68 Nodal status Negative vs positive 0.03 0.03 Known vs unknown 0.72 0.66 Metastasis at diagnosis No vs yes 0.01 <0.01 Serum CEA level (ng/mL) ≤6 vs >6 0.59 0.42 EGFR codon 497 polymorphism G/G (wild-type) vs G/A or A/A 0.02 0.03 NOTE: According to international TNM staging system for colorectal carcinoma.
Volume 13, Issue 12
