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Angeles Montero
Author of
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P2.09 - Pathology (Not CME Accredited Session) (ID 958)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.09-06 - Expression of PD-L1 on Routine Non-Small Cell Lung Carcinoma Sections: Comparative Assessment of SP263 (Ventana) and 22C3 (DAKO pharmDx) (ID 13019)
16:45 - 18:00 | Author(s): Angeles Montero
- Abstract
Background
The SP263 (Ventana Benchmark) antibody as a predictive immunohistochemical marker for pembrolizumab therapy provides an avenue for local testing. Pathologists without access to the Dako Autostainer Link 48 platform (certified for the Dako 22C3 antibody) have been restricted to referrals at external departments, resulting in an increased turnaround time. Here we report the results of our local verification of SP263.
a9ded1e5ce5d75814730bb4caaf49419 Method
Specimens previously assessed for 22C3 PD-L1 expression at either Royal Liverpool Hospital or Queen Elizabeth Hospital Birmingham were selected from the archives of Wythenshawe Hospital. Cases with less than 100 viable residual tumour cells were excluded. The same tumour block was selected for staining with the Roche SP263 clone and specimens were assessed for tumour proportion score (TPS), immune cell proportion and staining intensity. Assays were reported as disagreeing if a differing TPS changed the therapeutic cut-off ranges.
4c3880bb027f159e801041b1021e88e8 Result
Expression levels of 22C3 and SP263 were compared across 100 cases (43 resections, 26 biopsies, 26 lymph node aspirates, 5 node excisions); 59 adenocarcinomas, 33 squamous carcinomas, 8 not otherwise specified (70 primary, 30 metastatic). The TPS ranges (<1%, 1 - 49%, > 50%) were in agreement for 78 samples. Of the 22 cases with differing ranges, 15 reflected a TPS of <10% and 7 had greater differences e.g. 10% versus 60%. Reasons for discrepancies included faint membranous staining on a few of the 22C3 sections (not apparent on SP263), scoring of carcinoma in situ, possible scoring of cells at a deeper block level, and variation in interpretation by the scoring pathologists. The overall Pearson correlation coefficient (r) was 0.9025, p < 0.00001.
Table 1 Comparison of PD-L1 Ventana SP263 and Dako 22C3 tumour proportion scores SAMPLE DIAGNOSIS SP263 >/= 1% >/= 50% Liverpool
22C3
Birmingham
22C3
Discrepancy Pleural biopsy
Adenocarcinoma
1
No
No
1
N/A
No
Pleural biopsy
Adenocarcinoma
10
No
No
60
N/A
Yes
EBUS node
Metastatic adenocarcinoma
0
No
No
0
N/A
No
EBUS node
Metastatic adenocarcinoma
0
No
No
1
N/A
Yes
Resection
Adenocarcinoma
40
Yes
No
10
N/A
No
EBUS node
Metastatic squamous carcinoma
2
No
No
10
N/A
No
Resection
Adenocarcinoma
5
Yes
No
<1
N/A
Yes
EBUS node
Metastatic adenocarcinoma
0
No
No
0
N/A
No
Bronchial biopsy
Squamous carcinoma
10
Yes
No
70
N/A
Yes
Bronchial biopsy
Squamous carcinoma
0
No
No
0
N/A
No
EBUS node
Metastatic squamous carcinoma
<1
No
No
<1
N/A
No
EBUS node
Metastatic adenocarcinoma
<1
No
No
0
N/A
No
Bronchial biopsy
Squamous carcinoma
40
Yes
No
40
N/A
No
Resection
Squamous carcinoma
5
Yes
No
10
N/A
No
Lung biopsy
Adenocarcinoma
0
No
No
0
N/A
No
Lymph node biopsy
Metastatic adenocarcinoma
100
Yes
Yes
100
N/A
No
Resection
Adenocarcinoma
<1
No
No
N/A
<1
No
Lung biopsy
Adenocarcinoma
0
No
No
N/A
0
No
Resection
Adenocarcinoma
0
No
No
0
N/A
No
Resection
Adenocarcinoma
10
Yes
No
N/A
5 to 10
No
Resection
Adenocarcinoma
20
Yes
Yes
N/A
20-30
No
Resection
Squamous carcinoma
2 to 4
Yes
No
N/A
3 to 5
No
Bronchial biopsy
Squamous carcinoma
<1
No
No
N/A
<1
No
Bronchial biopsy
Squamous carcinoma
2 to 4
Yes
No
1
N/A
No
Lymph node biopsy
Metastatic adenocarcinoma
100
Yes
Yes
100
N/A
No
Bronchial biopsy
NOS
<1
No
No
N/A
<1
No
Bronchial biopsy
Adenocarcinoma
0
No
No
1
N/A
Yes
Resection
Adenocarcinoma
2 to 4
Yes
No
10
N/A
No
Lymph node biopsy
Metastatic squamous carcinoma
80
Yes
Yes
70
N/A
No
EBUS node
Metastatic adenocarcinoma
80
Yes
Yes
80
N/A
No
Bronchial biopsy
Squamous carcinoma
0
No
No
N/A
<1
No
EBUS node
Metastatic adenocarcinoma
90
Yes
Yes
80
N/A
No
Pleural biopsy
Adenocarcinoma
0
No
No
10
N/A
Yes
Bronchial biopsy
Squamous carcinoma
0
No
No
0
N/A
No
Bronchial biopsy
Squamous carcinoma
5
Yes
No
N/A
0
Yes
EBUS node
Metastatic squamous carcinoma
50
Yes
Yes
50
N/A
No
Bronchial biopsy
Squamous carcinoma
2 to 4
Yes
No
10
N/A
No
EBUS node
Metastatic adenocarcinoma
70
Yes
Yes
N/A
70
No
EBUS node
Metastatic adenocarcinoma
100
Yes
Yes
100
N/A
No
Bronchial biopsy
Squamous carcinoma
1
Yes
No
20
N/A
No
Resection
Adenocarcinoma
5
Yes
No
0
N/A
Yes
Resection
Adenocarcinoma
0
No
No
0
N/A
No
EBUS node
Adenocarcinoma
<1
No
No
0
N/A
No
Resection
Adenocarcinoma
5
Yes
No
10
N/A
No
EBUS node
Sarcomatoid carcinoma
0
No
No
0
N/A
No
Resection
Adenocarcinoma
0
No
No
N/A
<1
No
Lymph node biopsy
Metastatic squamous carcinoma
0
No
No
N/A
<1
No
Resection
Adenocarcinoma
60
Yes
Yes
N/A
60-70
No
Bronchial biopsy
Squamous carcinoma
0
No
No
0
N/A
No
Pleural biopsy
Adenocarcinoma
2 to 4
Yes
No
10
N/A
No
Lung biopsy
Squamous carcinoma
0
No
No
5
N/A
Yes
EBUS node
Metastatic adenocarcinoma
5
Yes
No
30
N/A
No
Resection
Pleomorphic carcinoma
70
Yes
Yes
80
N/A
No
Resection
Squamous carcinoma
0
No
No
1
N/A
Yes
Bronchial biopsy
Squamous carcinoma
10
Yes
No
20
N/A
No
Resection
Adenocarcinoma
50
Yes
Yes
N/A
10 to 20
Yes
Resection
Adenocarcinoma
0
No
No
N/A
<1
No
Resection
Pleomorphic carcinoma
1
Yes
No
20
N/A
No
Resection
Adenocarcinoma
0
No
No
0
N/A
No
Resection
Adenocarcinoma
10
Yes
No
N/A
2 to 3
No
EBUS node
Metastatic adenocarcinoma
100
Yes
Yes
100
N/A
No
Resection
Adenocarcinoma
5
Yes
No
N/A
<1
Yes
EBUS node
Metastatic adenocarcinoma
100
Yes
Yes
100
N/A
No
EBUS node
Metastatic squamous carcinoma
50
Yes
Yes
N/A
80
No
Resection
Adenocarcinoma
90
Yes
Yes
95
N/A
No
Resection
Adenocarcinoma
<1
No
No
N/A
<1
No
Resection
Adenocarcinoma
0
No
No
1
0
Yes
Resection
Adenocarcinoma
<1
No
No
5
N/A
Yes
Resection
Adenocarcinoma
20
Yes
No
20
N/A
No
Bronchial biopsy
NOS
50
Yes
Yes
60
N/A
No
Resection
Adenocarcinoma
2 to 4
Yes
No
N/A
5 to 10
No
Resection
Adenocarcinoma
0
No
No
10
N/A
Yes
Soft tissue
NOS
1
Yes
No
20
N/A
No
Bronchial biopsy
Sarcomatoid carcinoma
<1
No
No
N/A
<1
No
EBUS node
Metastatic adenocarcinoma
70
Yes
Yes
N/A
60 to 70
No
Pleural biopsy
Adenocarcinoma
80
Yes
Yes
N/A
70
No
Resection
Squamous carcinoma
<1
No
No
1
0
Yes
Resection
Adenocarcinoma
50
Yes
Yes
N/A
5 to 10
Yes
Resection
Adenocarcinoma
10
Yes
No
50
N/A
Yes
Resection
Adenocarcinoma
0
No
No
0
N/A
No
Resection
Squamous carcinoma
1
Yes
No
N/A
<1
Yes
Resection
Squamous carcinoma
100
Yes
Yes
100
N/A
No
Resection
Squamous carcinoma
5
Yes
No
10
No
Resection
Squamous carcinoma
70
Yes
Yes
N/A
70 to 80
No
Resection
Squamous carcinoma
90
Yes
Yes
N/A
10 to 20
Yes
EBUS node
Squamous carcinoma
<1
No
No
N/A
<1
No
EBUS node
Adenocarcinoma
0
No
No
N/A
0
No
EBUS node
Metastatic adenocarcinoma
70
Yes
Yes
N/A
80
No
EBUS node
Metastatic squamous carcinoma
50
Yes
No
N/A
70
No
Resection
Adenocarcinoma
<1
No
No
N/A
<1
No
EBUS node
Metastatic adenocarcinoma
40
Yes
No
30
N/A
No
Resection
Squamous carcinoma
90
Yes
Yes
N/A
100
No
Resection
Adenocarcinoma
40
Yes
No
40
N/A
No
EBUS node
Metastatic adenocarcinoma
80
Yes
Yes
N/A
70 to 80
No
EBUS node
Metastatic squamous carcinoma
1
Yes
No
N/A
<1
Yes
Bronchial biopsy
Squamous carcinoma
1
Yes
No
1
N/A
No
EBUS node
Metastatic adenocarcinoma
5
Yes
No
60
N/A
Yes
Primary EBUS
Pleomorphic carcinoma
100
Yes
Yes
90
N/A
No
Resection
Adenocarcinoma
90
Yes
Yes
90
N/A
No
Lymph node biopsy
Adenocarcinoma
<1
No
No
<1
N/A
No
Tumour expression profiles of PD-L1 are similar for the 22C3 and SP263 antibodies, with a rate of variation similar to previous reports. Cases that are discrepant may reflect differences in pathologist interpretation rather than the assay.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P3.09 - Pathology (Not CME Accredited Session) (ID 975)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.09-05 - Significance of the Expression of PD-L1/PD-1 by Tumoral and Immune Cells in Non-Small Cell Lung Cancer. (ID 14241)
12:00 - 13:30 | Author(s): Angeles Montero
- Abstract
Background
Non-Small Cell Lung Cancer (NSCLC) accounts for approximately 85% of all cases of lung cancer, including adenocarcinoma, squamous cell carcinoma and large cell carcinoma. There is solid evidence that demonstrates the existence of anti-tumor adaptive T-cell mediated immunity activation in lung tumors, indicating that lung cancers are immunogenic. PD-L1and PD-1 expression level in lung cancer may be a predictive biomarker for the use of PD1/PD-L1 inhibitors. However, the reproducibility of PD-L1 staining using different antibodies and platforms is still a matter of debate. We assessed whether PD-L1 expression in non-small cell lung cancer is associated with specific clinical features or survival using four different antibodies and if the expression of PD-1 in TILs correlates with the expression of PD-L1 in same group of cells.
a9ded1e5ce5d75814730bb4caaf49419 Method
PD-L1 and PD-1 status was assessed with IHC (AB clone SP142 and SP263 - Ventana, 22C3, 28-8 – Dako and PD-1) on archival FFPE surgical tumor specimens, arrayed on tissue microarrays (TMAs) with duplicate 1 mm cores, from Karolinska University Hospital. All patients (n = 598) underwent curative surgery between 1987 and 2015. The following cases were excluded from survival analysis (n = 89): R1 resection, early post-operative mortality, adjuvant chemo- or radiotherapy. PD-L1 staining was scored as positive if present in > 1% of tumor cells, independently of staining intensity.
4c3880bb027f159e801041b1021e88e8 Result
Patient and tumor characteristics were as follows. Median age (IQR): 68 years (27-89); gender: male/female 54%/46%; histology: squamous-cell carcinoma (SCC)/Non-squamous (N-Sq)-NSCLC/carcinoid 219 (32%)/394 (58%)/45(7%); p-stage: IA/IB/IIA/IIB/IIIA/IIIB 50%/26%/10%/10%/2%/0.2%. PD-L1 28-8 was positive in 11% of cases, Pearson Chi-square p<0.0001). PD-L1 positivity 22C3/SP263/SP142 was 10%/13%/3%. All carcinoids were negative for PD-L1. In NSCLC, PD-L1 positivity for each antibody was associated with tumor size (T1/T2-4; Fisher’s exact test, p<0.001) and grade of differentiation (G1, G2 and G3; p<0.0002). Statistically significant association between PD-L1 expression and OS was only observed using the clone SP263 (log-rank p=0.013). PD-1 expression in TILs correlates with those of PD-L1 (clone 28-8).
8eea62084ca7e541d918e823422bd82e Conclusion
In this surgical series, the clone SP142 showed less PD-L1 expression in the tumor cells. PD-L1 status was associated with tumor size, grading and only the clone SP263 showed association between its expression and survival ratio. PD-1 expression in TILs correlates with those of PD-L1.
6f8b794f3246b0c1e1780bb4d4d5dc53