Population characteristics
This study involved 461 Chinese NSCLC patients who performed with EGFR mutation and ALK&ROS1 fusion test. Three hundred and eleven were male and 150 were female. There were 349 (349/461, 75.7%) were adenocarcinoma, 106 (106/461, 23.0%) were squamous and 6 (6/461, 1.3%) were adenosquamous, respectively. HE staining and immunohistochemical staining for squamous cell carcinoma and lung adenocarcinoma are shown in Fig. 1. Most of these patients, 255 were nonsmokers (255/461, 55.3%) and 272 were older than 60 years old (272/461, 59.0%). Thirty-four (7.4%), 18 (3.9%), 90 (19.5%), and 319 (69.2%) patients were in stage I, II, III and IV, respectively. The clinical characteristics of patients are shown in Table 1.
Table 1
Characteristics of patients with lung cancer included in this study.
Parameter | n (%) |
Age (years) | |
≤ 60 | 189(41.0) |
༞60 | 272(59.0) |
Mean ± SD | 61.76 ± 10.34 |
Range | 27–87 |
Gender | |
Male | 311(67.5) |
Female | 150(32.5) |
Smoking status | |
Never smoked | 255(55.3) |
Smoking | 206(44.7) |
Pathology | |
Adenocarcinoma | 349(75.7) |
Squamous | 106(23.0) |
Adenosquamous | 6(1.3) |
Disease stage | |
I | 34(7.4) |
Ⅱ | 18(3.9) |
Ⅲ | 90(19.5) |
Ⅳ | 319(69.2) |
Comparisons of characteristics between EGFR-positive and ALK&ROS1-positive cases, ALK&ROS1-positive and non-ALK&ROS1/EGFR cases, and EGFR-positive and non-ALK&ROS1/EGFR cases in NSCLC patients
Of the 461 patients studied, we identified 175 cases of EGFR mutations in exons 18, 19, 20, or 21 (38.0%, 175/461). The G719X mutation (in exon 18) were identified in 3 cases (1.7%); exon 19 deletion were identified in 95 cases (54.3%), exon 20 insertion were detected in 2 cases (1.1%) and S768I mutation (in exon 20) was detected in 1 case (0.6%), L858R mutation (in exon 21) were detected in 66 cases (37.7%) and L861Q mutation (in exon 21) were detected in 8 cases (4.6%), respectively. ALK gene fusions were identified in 33 cases (33/461, 7.2%) and ROS1 gene fusions were identified in 9 cases (9/461, 1.9%).
Compared with the EGFR-positive group, the significant differences in ALK&ROS1-positive group was younger (P < 0.001). There were no significant differences in gender, smoking history, pathology, clinical stage, computed tomography characteristics (lymphangitic, lymphadenopathy, emphysema, fibrosis and pleural effusion).
Comparisons of characteristics between EGFR-positive and non- ALK&ROS1/EGFR cases in NSCLC patients. In the EGFR-positive group, the majority were female (50.9%, P < 0.001), non-smoking (76.6%, P < 0.001), adenocarcinoma (90.9%, P < 0.001) patients. In addition, there were significant difference in clinical stage (P = 0.002), emphysema (P < 0.001) and fibrosis (P = 0.021). There were no significant differences in age, lymphangitic, lymphadenopathy and pleural effusion.
Compared with the non-ALK&ROS1/EGFR cases in NSCLC patients, the ALK&ROS1-positive group that significantly differed from the non-ALK&ROS1/EGFR group were: younger (P < 0.001), the majority were female (52.4%, P < 0.001), non-smoking (66.7%, P = 0.001), adenocarcinoma (90.5%, P = 0.002) patients, appeared lymphangitic was more (23.8%, P = 0.044) and emphysema was less (9.5%, P < 0.001) (Table 2).
Table 2
Comparisons of characteristics between EGFR-positive and ALK&ROS1-positive cases, ALK&ROS1-positive and non-ALK&ROS1/EGFR cases, and EGFR-positive and non-ALK&ROS1/EGFR cases in NSCLC patients.
Patient characteristic | EGFR (+) (n = 175) | ALK&ROS1 fusion (+) (n = 42) | Non-ALK&ROS1/EGFR (n = 246) | P value |
EGFR (+) vs ALK&ROS1 fusion (+) | EGFR (+) vs Non-ALK&ROS1/EGFR | ALK fusion (+) vs Non-ALK&ROS1/EGFR |
No. (Total 461) | 175(38.0) | 42(9.1) | | | | |
Age | | | | < 0.001 | 0.477 (χ2 test) | < 0.001 |
≤ 60 | 70(40.0) | 31(73.8) | 90(36.6) | | | |
༞60 | 105(60.0) | 11(26.2) | 156(63.4) | | | |
Mean ± SD | 61.74 ± 9.82 | 54.90 ± 13.03 | 62.87 ± 9.78 | < 0.001 | 0.245 (t test) | < 0.001 |
Range | 27–86 | 30–85 | 28–87 | | | |
Gender | | | | 0.859 | < 0.001 | < 0.001 |
Male | 86(49.1) | 20(47.6) | 207(84.1) | | | |
Female | 89(50.9) | 22(52.4) | 39(15.9) | | | |
Smoking | | | | 0.185 | < 0.001 | 0.001 |
Never | 134(76.6) | 28(66.7) | 95(38.6) | | | |
Smoking | 41(23.4) | 14(33.3) | 151(61.4) | | | |
Pathology | | | | 0.634 | < 0.001 | 0.002 |
Adenocarcinoma | 159(90.9) | 38(90.5) | 154(62.6) | | | |
Squamous | 13(7.4) | 4(9.5) | 89(36.2) | | | |
Adenosquamous | 3(1.7) | 0(0) | 3(1.2) | | | |
Disease stage | | | | 0.268 | 0.002 | 0.368 |
I | 17(9.7) | 4(9.5) | 13(5.3) | | | |
Ⅱ | 10(5.7) | 0(0) | 8(3.3) | | | |
Ⅲ | 20(11.4) | 8(19.0) | 62(25.2) | | | |
Ⅳ | 128(73.1) | 30(71.4) | 163(66.3) | | | |
Lymphangitic | 29(16.6) | 10(23.8) | 30(12.2) | 0.273 | 0.202 | 0.044 |
Lymphadenopathy | 123(70.3) | 30(71.4) | 186(75.6) | 0.884 | 0.223 | 0.563 |
Emphysema | 26(14.9) | 4(9.5) | 103(41.9) | 0.369 | < 0.001 | < 0.001 |
Fibrosis | 15(8.6) | 2(4.8) | 40(16.3) | 0.536 | 0.021 | 0.051 |
Pleural effusion | 73(41.7) | 16(38.1) | 91(37.0) | 0.668 | 0.327 | 0.891 |
The association between EGFR, ALK&ROS1 genes status and clinical characteristics
Compared with EGFR-negative cases, in the EGFR-positive group, the most were female (50.9% vs 21.3%, P < 0.001), non-smoking (76.6% vs 42.3%, P < 0.001), adenocarcinoma (90.9% vs 66.4%, P < 0.001) patients. In addition, there were significant difference in clinical stage (P = 0.002) and emphysema (P < 0.001). There were no significant difference in age, lymphangitic, lymphadenopathy, fibrosis and pleural effusion.
Compared with ALK&ROS1-negative group, the ALK&ROS1-positive group was younger than ALK&ROS1-negative group (73.8% vs 37.7% in ≤ 60 years, P < 0.001). About the ALK&ROS1-positive group, the most were female (52.4% vs 30.5%, P = 0.004) patients, and emphysema was less (9.5% vs 30.8%, P = 0.004). There were no significant differences in smoking history, pathology, clinical stage, lymphangitic, lymphadenopathy, fibrosis and pleural effusion (Table 3).
Table 3
Analysis of the relationship between EGFR and ALK&ROS1 genes status and clinical characteristics.
| EGFR mutation | | ALK&ROS1 fusion | |
Characteristic | + | - | P value | + | - | P value |
No. (Total 461) | 175(38.0) | 286(62.0) | | 42(9.1) | 419(90.9) | |
Age | | | 0.733 | | | < 0.001 |
≤ 60 | 70(40.0) | 119(41.6) | | 31(73.8) | 158(37.7) | |
༞60 | 105(60.0) | 167(58.4) | | 11(26.2) | 261(62.3) | |
Gender | | | < 0.001 | | | 0.004 |
Male | 86(49.1) | 225(78.7) | | 20(47.6) | 291(69.5) | |
Female | 89(50.9) | 61(21.3) | | 22(52.4) | 128(30.5) | |
Smoking | | | < 0.001 | | | 0.121 |
Never | 134(76.6) | 121(42.3) | | 28(66.7) | 227(54.2) | |
Smoking | 41(23.4) | 165(57.7) | | 14(33.3) | 192(45.8) | |
Pathology | | | < 0.001 | | | 0.061 |
Adenocarcinoma | 159(90.9) | 190 (66.4) | | 38(90.5) | 311(74.2) | |
Squamous | 13(7.4) | 93(32.5) | | 4(9.5) | 102(24.3) | |
Adenosquamous | 3(1.7) | 3(1.0) | | 0(0) | 6(1.4) | |
Disease stage | | | 0.002 | | | 0.545 |
I | 17(9.7) | 17(5.9) | | 4(9.5) | 30(7.2) | |
Ⅱ | 10(5.7) | 8(2.8) | | 0(0) | 18(4.3) | |
Ⅲ | 20(11.4) | 70(24.5) | | 8(19.0) | 82(19.6) | |
Ⅳ | 128(73.1) | 191(66.8) | | 30(71.4) | 289(69.0) | |
Lymphangitic | 29(16.6) | 40(14.0) | 0.450 | 10(23.8) | 59(14.1) | 0.092 |
Lymphadenopathy | 123(70.3) | 214(74.8) | 0.286 | 30(71.4) | 307(73.3) | 0.798 |
Emphysema | 26(14.9) | 107(37.4) | < 0.001 | 4(9.5) | 129(30.8) | 0.004 |
Fibrosis | 15(8.6) | 42(14.7) | 0.053 | 2(4.8) | 55(13.1) | 0.116 |
Pleural effusion | 73(41.7) | 106(37.1) | 0.320 | 16(38.1) | 163(38.9) | 0.919 |
The relationship between various types of mutations in the EGFR gene and clinical characteristics
Among the exon 19 deletion, L858R, L861Q, G719X, exon 20 insertion and S768I mutations in EGFR, there were no significant differences in age and gender. The NSCLC patients with exon 19 deletion (74.7%) and L858R (86.4%) most were non-smokers, while patients with L861Q (62.5%) and G719 × (66.7%) most were smokers (Table 4). But the sample size of patients with L861Q, G719X, exon 20 insertion and S768I in our study is relatively small, and this result cannot represent the actual situation and we need a large sample size to analyze this problem.
Table 4
Analysis of the relationship between various types of mutations in the EGFR gene and clinical characteristics.
Characteristic | Exon 19 deletion | L858R | L861Q | G719X | Exon 20 insertion | S768I | P value |
No. (Total 175) | 95(54.3) | 66(37.7) | 8(4.6) | 3(1.7) | 2(1.1) | 1(0.6) | |
Age | | | | | | | 0.059 |
≤ 60 | 47(49.5) | 19(28.8) | 2(25.0) | 1(33.3) | 0(100) | 1(100) | |
༞60 | 48(50.5) | 47(71.2) | 6(75.0) | 2(66.7) | 2(100) | 0(0) | |
Gender | | | | | | | 0.199 |
Male | 47(49.5) | 28(42.4) | 7(87.5) | 2(66.7) | 1(50.0) | 1(100) | |
Female | 48(50.5) | 38(57.6) | 1(12.5) | 1(33.3) | 1(50.0) | 0(0) | |
Smoking | | | | | | | 0.012 |
Never | 71(74.7) | 57(86.4) | 3(37.5) | 1(33.3) | 1(50.0) | 1(100) | |
Smoking | 24(25.3) | 9(13.6) | 5(62.5) | 2(66.7) | 1(50.0) | 0(0) | |