Cytology Smears in the Era of Molecular Biomarkers in Non–Small Cell Lung Cancer: Doing More With Less

Lozano, Marı́a D.; Echeveste, José; Abengózar, Marta; Mejías, Luis D.; Idoate, Miguel A.; Calvo, Alfonso; Andrea, Carlos E. de

doi:10.5858/arpa.2017-0208-ra

Cited by 60 publications

(70 citation statements)

References 57 publications

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“…Cell integrity can be assessed, and the method can be applied to different biological specimens, such as biopsies or cytological samples. Its use in cytology smears is quite controversial, although recent studies have proven the suitability of the method [28]. The most commonly used antibodies are D5F3 (Ventana ALK [D5F3] CDx Assay, Tucson, Arizona, USA) and 5A4 (Novocastra, Leica Biosystems, Buffalo Grove, Illinois, USA), although the latter is not included in a diagnostic kit [29].…”

Section: Egfrmentioning

confidence: 99%

Updated guidelines for predictive biomarker testing in advanced non-small-cell lung cancer: a National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology

et al. 2019

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In 2011 the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP) started a joint project to establish guidelines on biomarker testing in patients with advanced non-small-cell lung cancer (NSCLC) based on current evidence. As this field is constantly evolving, these guidelines have been updated, previously in 2012 and 2015 and now in 2019. Current evidence suggests that the mandatory tests to conduct in all patients with advanced NSCLC are for EGFR and BRAF mutations, ALK and ROS1 rearrangements and PD-L1 expression. The growing need to study other emerging biomarkers has promoted the routine use of massive sequencing (next-generation sequencing, NGS). The coordination of every professional involved and the prioritisation of the most suitable tests and technologies for each case remains a challenge.

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Section: Egfrmentioning

confidence: 99%

Updated guidelines for predictive biomarker testing in advanced non-small-cell lung cancer: a National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology

et al. 2019

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“…In patients with lung cancer, pathologists are increasingly facing the challenge of performing more molecular tests on smaller biopsy specimens generally obtained from minimally invasive procedures . A large number of cases of advanced NSCLC are diagnosed on cytology specimens alone .…”

Section: Introductionmentioning

confidence: 99%

Programmed death–ligand 1 expression on direct Pap‐stained cytology smears from non–small cell lung cancer: Comparison with cell blocks and surgical resection specimens

Lozano

Abengozar-Muela

Echeveste

et al. 2019

Cancer Cytopathology

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Background Programmed death–ligand 1 (PD‐L1) expression, as assessed by immunohistochemistry (IHC), is used to select patients with non–small cell lung cancer (NSCLC) for anti‐programmed cell death protein 1 (PD‐1)/PD‐L1 therapy. The current study evaluated the feasibility and efficacy of PD‐L1 immunostaining and quantitation on direct Papanicolaou‐stained cytological smears compared with formalin‐fixed paraffin‐embedded samples (cytological cell blocks and surgical resection specimens) in NSCLC cases using 2 commercially available assays: the PD‐L1 IHC 22C3 pharmDx assay (Agilent Technologies/Dako, Carpinteria, CA, USA) and the Ventana SP263 Assay (Ventana Medical Systems Inc, Tucson, Arizona). Methods PD‐L1 immunostaining using either both or one of the assays was tested in 117 sets of paired samples obtained from 62 NSCLC cases. The tumor proportion score was reported in every case following the recommendations of the International Association for the Study of Lung Cancer (IASLC). Results In 57 sets of samples, both PD‐L1 assays were used. Due to the availability of samples, only 1 assay was performed in 3 sets of samples and in 2 cases, only cytology smears were used and tested for both assays. A total of 113 sets of paired samples finally were evaluated; 4 cases could not be studied due to intense nonspecific background staining. A significant concordance between the 2 assays on cytological smears was found. Concordance between paired cytological smears and formalin‐fixed paraffin‐embedded samples was observed in 97.3% of the cases. Conclusions The quantification of PD‐L1 expression on direct Papanicolaou‐stained cytology smears is feasible and reliable for both PD‐L1 assays.

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“…After validation by AccuRef Diagnostics, the sets of unstained slides (A‐D) were distributed to the 17 laboratories; some of the laboratories that specialized in NGS testing of cytological samples had also taken part in the working group of the latest annual meeting on molecular cytopathology held in Naples, Italy (Fig. ) . Each laboratory stained the slides by applying their own routine protocols (Diff Quik, Papanicolaou, or hematoxylin‐eosin staining).…”

Section: Methodsmentioning

confidence: 99%

Consistency and reproducibility of next‐generation sequencing in cytopathology: A second worldwide ring trial study on improved cytological molecular reference specimens

Pisapia

Malapelle

Roma

et al. 2019

Cancer Cytopathology

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Background Artificial genomic reference standards in a cytocentrifuge/cytospin format with well‐annotated genomic data are useful for validating next‐generation sequencing (NGS) on routine cytopreparations. Here, reference standards were optimized to be stained by different laboratories before DNA extraction and to contain a lower number of cells (2 × 105). This was done to better reflect the clinical challenge of working with insufficient cytological material. Methods A total of 17 worldwide laboratories analyzed customized reference standard slides (slides A‐D). Each laboratory applied its standard workflow. The sample slides were engineered to harbor epidermal growth factor receptor (EGFR) c.2235_2249del15 p.E746_A750delELREA, EGFR c.2369C>T p.T790M, Kirsten rat sarcoma viral oncogene homolog (KRAS) c.38G>A p.G13D, and B‐Raf proto‐oncogene, serine/threonine kinase (BRAF) c.1798_1799GT>AA p.V600K mutations at various allele frequencies (AFs). Results EGFR and KRAS mutation detection showed excellent interlaboratory reproducibility, especially on slides A and B (10% and 5% AFs). On slide C (1% AF), either the EGFR mutation or the KRAS mutation was undetected by 10 of the 17 laboratories (58.82%). A reassessment of the raw data in a second‐look analysis highlighted the mutations (n = 10) that had been missed in the first‐look analysis. BRAF c.1798_1799GT>AA p.V600K showed a lower concordance rate for mutation detection and AF quantification. Conclusions The data show that the detection of low‐abundance mutations is still clinically challenging and may require a visual inspection of sequencing reads to detect. Genomic reference standards in a cytocentrifuge/cytospin format are a valid tool for regular quality assessment of laboratories performing molecular studies on cytology with low‐AF mutations.

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Cytology Smears in the Era of Molecular Biomarkers in Non–Small Cell Lung Cancer: Doing More With Less

Cited by 60 publications

References 57 publications

Updated guidelines for predictive biomarker testing in advanced non-small-cell lung cancer: a National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology

Updated guidelines for predictive biomarker testing in advanced non-small-cell lung cancer: a National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology

Programmed death–ligand 1 expression on direct Pap‐stained cytology smears from non–small cell lung cancer: Comparison with cell blocks and surgical resection specimens

Consistency and reproducibility of next‐generation sequencing in cytopathology: A second worldwide ring trial study on improved cytological molecular reference specimens

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