Publicaciones científicas

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

01-mar-2018 | Revista: Archives of Pathology & Laboratory Medicine

Lozano MDEcheveste JIAbengozar M, Mejías LD, Idoate MA, Calvo A, de Andrea CE (1).

(1) From the Department of Pathology, Clínica Universidad de Navarra, (Drs Lozano, Echeveste, Abengozar, Mejías, Idoate, and de Andrea), IDISNA and Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA) (Dr Calvo), and the Department of Histology and Pathology (Drs Calvo and de Andrea), University of Navarra, Pamplona, Spain.


The rapid advances in targeted therapies in non-small cell lung cancer (NSCLC) make the optimization and implementation of cytology specimens for molecular testing a priority. Up to 70% of patients with NSCLC are diagnosed at advanced stages and tissue biopsies often cannot be taken. Although cytology samples provide high-quality material for molecular testing, molecular cytopathology is not yet well known or widely used.


To report the many advances in molecular cytopathology and the suitability and utility of cytology samples in molecular and genetic testing of NSCLC.


Data sources comprised published peer-reviewed literature and personal experience of the authors.


Molecular testing can be performed on cytologic specimens, especially on direct smears. Rapid on-site evaluation by cytopathologists has improved the adequacy and the management of cytology samples for molecular testing.

Mutational profiling of NSCLC using next-generation sequencing can be performed on cytology samples from very small amounts of DNA. Fluorescence in situ hybridization assays on cytology specimens, including stained direct smear, offer some distinct advantages over their histologic counterpart, and are used to detect ALK and ROS1 rearrangements in NSCLC.

Cytology specimens allow assessment of the entire tumor cell nucleus, avoiding signal loss from truncation artifacts. The use of cytology samples for assessing programmed death ligand-1 protein expression is currently being developed.

Protocols for bisulfite conversion and DNA droplet digital polymerase chain reaction assays have been optimized for cytology smear to investigate aberrant DNA methylation of several NSCLC-related genes.

CITA DEL ARTÍCULO  Arch Pathol Lab Med. 2018 Mar;142(3):291-298. doi: 10.5858/arpa.2017-0208-RA