Background
Methods
Case collection
Immunohistochemistry (IHC)
Antibody
|
Source
|
Clonality
|
Clone
|
Species
|
Dilution
|
Pretreatment
|
---|---|---|---|---|---|---|
TTF-1 | Ventana | Monoclonal | 8G7G3/1 | Mouse | Prediluted | CC1 |
Napsin A | Novocastra | Monoclonal | IP64 | Mouse | 1:800 | Bond enzyme |
CK7 | Dako | Monoclonal | Ov-tl | Mouse | 1:500 | None |
P63 | BioCare | Monoclonal | 4a4 | Mouse | Prediluted | CC1 |
CK5/6 | Ventana | Monoclonal | D5/16 B4 | Mouse | Prediluted | CC1 |
Statistical analysis
Results and discussion
Clinical information
Characteristics
|
Primary lung tumor
|
Metastatic lung tumor
|
P Value
|
---|---|---|---|
Sex* (cases (%)) | 0.3638 | ||
Male | 46 (45.5%) | 75 (52.1%) | |
Female | 55 (54.5%) | 69 (47.9%) | |
Age (years) | 0.4110 | ||
Average ± SD | 65.0 ± 11.2 | 63.8 ± 11.3 | |
Median | 67.0 | 64.0 | |
Range | 29-85 | 32-89 | |
Adenocarcinomas | 72 (70.6%) | 131 (91.0%) | N/A |
Squamous cell carcinomas | 30 (29.4%) | 13 (9.0%) | |
Total cases | 102 | 144 | N/A |
Sites of Metastatic NSCLC
|
Cases (Percentage)
|
---|---|
Adenocarcinoma (n = 131)
| |
Lymph node | 59 (45.0%) |
Pleural fluid | 40 (30.5%) |
Soft tissue | 8 (6.1%) |
Bone | 7 (5.3%) |
Liver | 6 (4.6%) |
Pericardial fluid | 4 (3.1%) |
Peritoneal fluid | 3 (2.3%) |
Other organs | 4 (3.1%) |
Squamous cell carcinoma (n = 13)
| |
Lymph node | 6 (46.2%) |
Pleural fluid | 3 (23.1%) |
Soft tissues | 3 (23.1%) |
Other organs | 1 (7.7%) |
Individual staining patterns of CK5/6 and P63 in SqCCs
NSCLC
|
P63
|
CK5/6
|
Napsin A
|
TTF-1
|
CK7
|
---|---|---|---|---|---|
Positive/total
|
Positive/total
|
Positive/total
|
Positive/total
|
Positive/total
| |
(%)
|
(%)
|
(%)
|
(%)
|
(%)
| |
Primary lung carcinomas (n = 102)
| |||||
ADC (n = 72)
| 5/23 | 2/9 | 23/25 | 60/71 | 45/48 |
(21.7%) | (22.2%) | (92.0%) | (84.5%) | (93.8%) | |
SqCC (n = 30)
| 22/24 | 18/18 | 0/8 | 1/28 | 7/14 |
(91.7%) | (100.0%) | (0.0%) | (3.6%) | (50.0%) | |
Metastatic tumor of the lung (n = 143)
| |||||
ADC (n = 131)
| 6/19 | 2/13 | 40/59 | 113/130 | 101/101 |
(31.6%) | (15.4%) | (67.8%) | (86.9%) | (100.0%) | |
SqCC (n = 13)
| 11/11 | 6/6 | 0/3 | 1/8 | 3/4 |
(100.0%) | (100.0%) | (0.0%) | (12.5%) | (75.0%) |
Type
|
Primary SqCC (n = 30) vs
|
Metastatic SqCC (n = 13) vs
| ||||||
---|---|---|---|---|---|---|---|---|
Primary ADC (n = 72)
|
Metastatic ADC (n = 131)
| |||||||
Sensitivity
|
Specificity
|
PPV
|
NPV
|
Sensitivity
|
Specificity
|
PPV
|
NPV
| |
P63
| 91.7% | 78.3% | 81.5% | 90.0% | 100.0% | 68.4% | 64.7% | 100.0% |
CK5/6
| 100.0% | 77.8% | 90.0% | 100.0% | 100.0% | 84.6% | 75.0% | 100.0% |
Staining patterns of TTF-1, Napsin A and CK7 in ADCs
Type
|
Primary ADC (n = 72) vs
|
Metastatic ADC (n = 131) vs
| ||||||
---|---|---|---|---|---|---|---|---|
Primary SqCC(n = 30)
|
Metastatic SqCC(n = 13)
| |||||||
Sensitivity
|
Specificity
|
PPV
|
NPV
|
Sensitivity
|
Specificity
|
PPV
|
NPV
| |
TTF-1
| 84.5% | 96.4% | 98.4% | 71.1% | 86.9% | 87.5% | 99.1% | 29.2% |
CK7
| 93.8% | 50.0% | 86.5% | 70.0% | 100.0% | 25.0% | 97.1% | 100.0% |
Napsin A
| 92.0% | 100.0% | 100.0% | 80.0% | 67.8% | 100.0% | 100.0%% | 13.6% |
The combination of IHC markers in NSCLCs
Markers
|
Sensitivity
|
Specificity
| ||
---|---|---|---|---|
Average ± SD
|
Range
|
Average ± SD
|
Range
| |
Primary ADCs
| ||||
TTF-1
| 0.848 ± 0.0446 | 0.690 – 0.972 | 0.934 ± 0.0438 | 0.800 – 1.000 |
Napsin A
| 0.919 ± 0.0545 | 0.720 – 1.000 | 1.000 ± 0.0000 | 1.000 – 1.000 |
CK7
| 0.941 ± 0.0330 | 0.833 – 1.000 | 0.489 ± 0.1432 | 0.077 – 0.769 |
TTF-1 + CK7
| 0.960 ± 0.0231 | 0.718 – 0.986 | 0.732 ± 0.0919 | 0.533 – 0.967 |
TTF-1 + Napsin
| 0.858 ± 0.0420 | 0.875 – 1.000 | 0.934 ± 0.0417 | 0.833 – 1.000 |
TTF-1 + CK7 + Napsin A
| 0.972 ± 0.0197 | 0.887 – 1.000 | 0.737 ± 0.0850 | 0.500 – 0.900 |
Metastatic ADCs
| ||||
TTF-1
| 0.870 ± 0.0310 | 0.808 – 0.946 | 0.870 ± 0.1243 | 0.500 – 1.000 |
Napsin A
| 0.702 ± 0.0647 | 0.559 – 0.881 | 1.000 ± 0.0000 | 1.000 – 1.000 |
CK7
| 1.000 ± 0.0000 | 1.000 – 1.000 | 0.285 ± 0.2358 | 0.000 – 1.000 |
TTF-1 + CK7
| 0.992 ± 0.0086 | 0.969 – 1.000 | 0.624 ± 0.1662 | 0.125 – 1.000 |
TTF-1 + Napsin
| 0.878 ± 0.0298 | 0.794 – 0.939 | 0.881 ± 0.1286 | 0.375 – 1.000 |
TTF-1 + CK7 + Napsin A
| 0.993 ± 0.0072 | 0.969 – 1.000 | 0.618 ± 0.1793 | 0.125 – 1.000 |
Markers
|
Sensitivity
|
Specificity
| ||
---|---|---|---|---|
Average ± SD
|
Range
|
Average ± SD
|
Range
| |
Primary SqCCs
| ||||
P63
| 0.921 ± 0.0557 | 0.750 – 1.000 | 0.780 ± 0.0913 | 0.522 – 0.957 |
CK5/6
| 1.000 ± 0.0000 | 1.000 – 1.000 | 0.769 ± 0.1410 | 0.333 – 1.000 |
P63 + CK5/6
| 1.000 ± 0.0000 | 1.000 – 1.000 | 0.766 ± 0.0872 | 0.480 – 0.920 |
Metastatic SqCCs
| ||||
P63
| 1.000 ± 0.0000 | 1.000 – 1.000 | 0.691 ± 0.1068 | 0.421 – 0.947 |
CK5/6
| 1.000 ± 0.0000 | 1.000 – 1.000 | 0.839 ± 0.1009 | 0.615 – 1.000 |
P63 + CK5/6
| 1.000 ± 0.0000 | 1.000 – 1.000 | 0.716 ± 0.0901 | 0.500 – 0.857 |