Abstract
Immunotherapy with checkpoint inhibitors, allowing recovery of effector cells function, has demonstrated to be highly effective in many tumor types and represents a true revolution in oncology. Recently, the anti-PD1 agent pembrolizumab was granted FDA approval for the first line treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumors show PD-L1 expression in ≥ 50% of neoplastic cells and as a second line treatment for patients with NSCLC expressing PD-L1 in ≥1% of neoplastic cells, evaluated with a validated assay. For the large majority of patients such evaluation is made on small biopsies. However, small tissue samples such as core biopsies might not be representative of tumors and may show divergent results given the possible heterogeneous immunoexpression of the biomarker. We therefore sought to evaluate PD-L1 expression concordance in a cohort of 239 patients using tissue microarrays (TMA) as surrogates of biopsies stained with a validated PD-L1 immunohistochemical assay (SP263) and report the degree of discordance among tissue cores in order to understand how such heterogeneity could affect decisions regarding therapy. We observed a discordance rate of 20% and 7.9% and a Cohen's κ value of 0.53 (moderate) and 0,48 (moderate) for ≥ 1% and ≥ 50% cutoffs, respectively. Our results suggest that caution must be taken when evaluating single biopsies from patients with advanced NSCLC eligible for immunotherapy; moreover, at least 4 biopsies are necessary in order to minimize the risk of tumor misclassification.
| Original language | English |
|---|---|
| Pages (from-to) | 90123-90131 |
| Number of pages | 9 |
| Journal | Oncotarget |
| Volume | 8 |
| Issue number | 52 |
| DOIs | |
| Publication status | Published - Jan 1 2017 |
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Keywords
- Immunotherapy
- Lung cancer
- PD-L1
- Pembrolizumab
- SP263
ASJC Scopus subject areas
- Oncology
Cite this
PD-L1 expression heterogeneity in non-small cell lung cancer : Evaluation of small biopsies reliability. / Munari, Enrico; Zamboni, Giuseppe; Marconi, Marcella; Sommaggio, Marco; Brunelli, Matteo; Martignoni, Guido; Netto, George J.; Moretta, Francesca; Mingari, Maria Cristina; Salgarello, Matteo; Terzi, Alberto; Picece, Vincenzo; Pomari, Carlo; Lunardi, Gianluigi; Cavazza, Alberto; Rossi, Giulio; Moretta, Lorenzo; Bogina, Giuseppe.
In: Oncotarget, Vol. 8, No. 52, 01.01.2017, p. 90123-90131.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - PD-L1 expression heterogeneity in non-small cell lung cancer
T2 - Evaluation of small biopsies reliability
AU - Munari, Enrico
AU - Zamboni, Giuseppe
AU - Marconi, Marcella
AU - Sommaggio, Marco
AU - Brunelli, Matteo
AU - Martignoni, Guido
AU - Netto, George J.
AU - Moretta, Francesca
AU - Mingari, Maria Cristina
AU - Salgarello, Matteo
AU - Terzi, Alberto
AU - Picece, Vincenzo
AU - Pomari, Carlo
AU - Lunardi, Gianluigi
AU - Cavazza, Alberto
AU - Rossi, Giulio
AU - Moretta, Lorenzo
AU - Bogina, Giuseppe
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Immunotherapy with checkpoint inhibitors, allowing recovery of effector cells function, has demonstrated to be highly effective in many tumor types and represents a true revolution in oncology. Recently, the anti-PD1 agent pembrolizumab was granted FDA approval for the first line treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumors show PD-L1 expression in ≥ 50% of neoplastic cells and as a second line treatment for patients with NSCLC expressing PD-L1 in ≥1% of neoplastic cells, evaluated with a validated assay. For the large majority of patients such evaluation is made on small biopsies. However, small tissue samples such as core biopsies might not be representative of tumors and may show divergent results given the possible heterogeneous immunoexpression of the biomarker. We therefore sought to evaluate PD-L1 expression concordance in a cohort of 239 patients using tissue microarrays (TMA) as surrogates of biopsies stained with a validated PD-L1 immunohistochemical assay (SP263) and report the degree of discordance among tissue cores in order to understand how such heterogeneity could affect decisions regarding therapy. We observed a discordance rate of 20% and 7.9% and a Cohen's κ value of 0.53 (moderate) and 0,48 (moderate) for ≥ 1% and ≥ 50% cutoffs, respectively. Our results suggest that caution must be taken when evaluating single biopsies from patients with advanced NSCLC eligible for immunotherapy; moreover, at least 4 biopsies are necessary in order to minimize the risk of tumor misclassification.
AB - Immunotherapy with checkpoint inhibitors, allowing recovery of effector cells function, has demonstrated to be highly effective in many tumor types and represents a true revolution in oncology. Recently, the anti-PD1 agent pembrolizumab was granted FDA approval for the first line treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumors show PD-L1 expression in ≥ 50% of neoplastic cells and as a second line treatment for patients with NSCLC expressing PD-L1 in ≥1% of neoplastic cells, evaluated with a validated assay. For the large majority of patients such evaluation is made on small biopsies. However, small tissue samples such as core biopsies might not be representative of tumors and may show divergent results given the possible heterogeneous immunoexpression of the biomarker. We therefore sought to evaluate PD-L1 expression concordance in a cohort of 239 patients using tissue microarrays (TMA) as surrogates of biopsies stained with a validated PD-L1 immunohistochemical assay (SP263) and report the degree of discordance among tissue cores in order to understand how such heterogeneity could affect decisions regarding therapy. We observed a discordance rate of 20% and 7.9% and a Cohen's κ value of 0.53 (moderate) and 0,48 (moderate) for ≥ 1% and ≥ 50% cutoffs, respectively. Our results suggest that caution must be taken when evaluating single biopsies from patients with advanced NSCLC eligible for immunotherapy; moreover, at least 4 biopsies are necessary in order to minimize the risk of tumor misclassification.
KW - Immunotherapy
KW - Lung cancer
KW - PD-L1
KW - Pembrolizumab
KW - SP263
UR - http://www.scopus.com/inward/record.url?scp=85032269559&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85032269559&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.21485
DO - 10.18632/oncotarget.21485
M3 - Article
VL - 8
SP - 90123
EP - 90131
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 52
ER -