Research Papers:

This article has been corrected. Correction in: Oncotarget. 2018; 9:37077.

PD-L1 expression heterogeneity in non-small cell lung cancer: evaluation of small biopsies reliability

Enrico Munari _, Giuseppe Zamboni, Marcella Marconi, Marco Sommaggio, Matteo Brunelli, Guido Martignoni, George J. Netto, Francesca Moretta, Maria Cristina Mingari, Matteo Salgarello, Alberto Terzi, Vincenzo Picece, Carlo Pomari, Gianluigi Lunardi, Alberto Cavazza, Giulio Rossi, Lorenzo Moretta and Giuseppe Bogina

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Oncotarget. 2017; 8:90123-90131. https://doi.org/10.18632/oncotarget.21485

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Enrico Munari1,2, Giuseppe Zamboni1, Marcella Marconi1, Marco Sommaggio1, Matteo Brunelli2, Guido Martignoni2,3, George J. Netto4, Francesca Moretta5, Maria Cristina Mingari6, Matteo Salgarello7, Alberto Terzi8, Vincenzo Picece9, Carlo Pomari10, Gianluigi Lunardi9, Alberto Cavazza11, Giulio Rossi12, Lorenzo Moretta13 and Giuseppe Bogina1

1Department of Pathology, Sacro Cuore Don Calabria Hospital, Negrar, Italy

2Department of Pathology AOUI, University of Verona, Verona, Italy

3Department of Pathology, Pederzoli Hospital, Peschiera del Garda, Italy

4Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL, USA

5Department of Laboratory Medicine, Sacro Cuore Don Calabria Hospital, Negrar, Italy

6Department of Experimental Medicine (DIMES), University of Genoa, Genoa, Italy

7Department of Nuclear Medicine, Sacro Cuore Don Calabria Hospital, Negrar, Italy

8Department of Thoracic Surgery, Sacro Cuore Don Calabria Hospital, Negrar, Italy

9Department of Oncology, Sacro Cuore Don Calabria Hospital, Negrar, Italy

10Department of Pulmonology, Sacro Cuore Don Calabria Hospital, Negrar, Italy

11Department of Pathology, Arcispedale S. Maria Nuova/IRCCS, Reggio Emilia, Italy

12Department of Pathology, Azienda USL Valle d'Aosta, Aosta, Italy

13Immunology Research Area, IRCCS Bambino Gesu Pediatric Hospital, Rome, Italy

Correspondence to:

Enrico Munari, email: [email protected]

Keywords: PD-L1, lung cancer, immunotherapy, SP263, pembrolizumab

Received: July 12, 2017     Accepted: August 27, 2017     Published: October 04, 2017


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.

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