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R. Langer
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P2.01 - Poster Session with Presenters Present (ID 461)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.01-052 - High PD-L1 Expression is Associated with Worse Prognosis in Primary Resected Squamous Cell Carcinomas of the Lung (ID 4787)
14:30 - 14:30 | Author(s): R. Langer
- Abstract
Background:
Expression of programmed death ligand 1 (PD-L1) is rendered a possible biomarker for immunotherapy targeting programmed death protein 1 (PD1) and PD-L1. Durable clinical responses have been demonstrated in patients with squamous cell carcinoma (SqCC) of the lung. Tumor infiltrating lymphocytes (TILs) are also regarded important players in immunomodulating therapies. Still, there is much uncertainty regarding the expression of the markers and associated tumor characteristics. We aimed to assess the prognostic impact and heterogeneity of PD-L1 expression across two antibodies, in conjunction with TILs, in SqCC of the lung.
Methods:
PD-L1 expression was investigated on a tissue microarray (TMA) of pulmonary SqCC using immunohistochemistry and two different clones (SP142, E1L3N). The cohort comprised all consecutive patients with primary resected pulmonary SqCC, without previous SqCC of other sites, diagnosed 2000-2013 at the Institute of Pathology, University of Bern. Epithelial expression of PD-L1 in primary tumors (n=372) and mediastinal lymph node (LN) metastases (n=27) was evaluated across 8 TMA cores per tumor using the following increment intervals: 0%; 1%; 5%; 10%; 20%; 30%, 50%. Intratumoral and intraepithelial infitrates of CD8+ T lymphocytes were determined. Results were compared with clinic-pathologic parameters including tumor related survival.
Results:
The staining results correlated significantly between the two antibodies (r=0.822; p<0.001) with the best congruence for tumors with ≤1% or ≥30% positivity. These tumors had also very homogenous staining results across all TMA cores, indicating low levels of intratumoral heterogeneity, in contrast to tumors with 1-30% PD-L1 positivity (p<0.001 both antibodies). Stainings correlated significantly between primary tumors and LN metastases (p<0.001 both antibodies). High PD-L1 expression correlated with intratumoral and intraepithelial CD8+ lymphocyte counts in primaries (p<0.001 both antibodies). PD-L1 expression was not significantly associated with pT or pN staging. High PD-L1 expression was associated with shorter tumor related survival. Cut-offs with the best prognostic discrimination were 30% positivity for SP142 and 50% for E1LN3 in univariate analysis (p=0.001/p=0.008). PD-L1 expression, pT category and age of the patients, but not CD8+ TILs were independent prognostic factors in multivariate analysis (HR=2.265, p=0.013 for SP142; HR=2.323, p=0.014 for E1LN3).
Conclusion:
PD-L1 expression was an independent predictor of shorter tumor related survival in pulmonary SqCC across all stages. The homogeneity of PD-L1 expression in “no” or “high” staining tumors across different cores and primary versus LN metastases indicates a valid assessment on small tissue samples and LN-metastases.
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P2.04 - Poster Session with Presenters Present (ID 466)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.04-026 - Expression Patterns of PD-L1 in Esophageal Adenocarcinomas: Comparison between Primary Tumors and Metastases (ID 5280)
14:30 - 14:30 | Author(s): R. Langer
- Abstract
Background:
Immune checkpoint inhibition through PD-L1 (Programmed death-ligand 1) is a powerful therapeutic option for many solid tumors, potentially including esophageal adenocarcinomas (EAC). Immunohistochemical expression analysis of PD-L1 may be helpful for guiding therapeutic decisions, but testing may be influenced by heterogeneous staining patterns within tumors and expression changes during metastatic course.
Methods:
We investigated PD-L1 expression in EAC using tissue microarrays from 116 primary resected tumors, corresponding lymph nodes (n=56) and distant metastases (n=18). PD-L1 expression was analyzed using two different antibodies (SP142 and E1LN3), together with intratumoral CD3+ and CD8+ T-lymphocyte (TIL) counts. In addition, preoperative biopsies and full slide sections from a subset of tumors (n=24) were investigated.
Results:
PD-L1 expression was first scored as 0%, >0-<1%, >1%, >5%, >50% positive membranous staining of tumor cells and of tumor associated inflammatory infiltrates and/or stroma cells. There was a significant correlation between the results of full slide sections and 12 cores/tumor containing TMAs (p=0.001), but not with the corresponding biopsies. For further analysis, PD-L1 positivity was defined as >1% positive staining for tumor cells and/or inflammatory and stroma cells according to the majority of current drug trails. We observed a very good concordance between the two antibodies for overall staining (p<0.001; concordance rate 89.5%). SP142 appeared slightly superior in terms of a more homogenous staining pattern. PD-L1 expression in tumor cells was detected by SP142 in 3 cases (2.6%) of primary EAC, whereas expression in the inflammatory and stromal cells was observed in 35 cases (30.2%). PD-L1 positive tumors had higher CD3+ and CD8+ TIL counts (p<0.001 and p=0.001) but no other distinct pathological or clinical features. Of note, there was no significant correlation between tumoral PD-L1 expression in primary tumors and lymph node and distant metastases.
Conclusion:
EAC show tumoral PD-L1expression only a minority of cases, whereas PD-L1 positivity in the inflammatory and stromal cells can be detected in a significant subset of cases. For the determination of PD-L1 status, it should be taken into account that PD-L1 expression in metastases may differ from primary tumors. Moreover, investigation of superficial small biopsies may produce false staining results, which, however, may be more likely be due to fixation artifacts or vicinity to ulceration than to intratumoral heterogeneity.
