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The Utilization of Cytologic Fine-Needle Aspirates of Lung Cancer for Molecular Diagnostic Testing.

Roh MH - J Pathol Transl Med (2015)

Bottom Line: In this era of precision medicine, our understanding and knowledge of the molecular landscape associated with lung cancer pathogenesis continues to evolve.During the management of these patients, minimally invasive procedures to obtain samples for tissue diagnoses are desirable.Thus, cytologic fine-needle aspirates must be utilized and triaged judiciously to achieve both objectives.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA.

ABSTRACT
In this era of precision medicine, our understanding and knowledge of the molecular landscape associated with lung cancer pathogenesis continues to evolve. This information is being increasingly exploited to treat advanced stage lung cancer patients with tailored, targeted therapy. During the management of these patients, minimally invasive procedures to obtain samples for tissue diagnoses are desirable. Cytologic fine-needle aspirates are often utilized for this purpose and are important not only for rendering diagnoses to subtype patients' lung cancers, but also for ascertaining molecular diagnostic information for treatment purposes. Thus, cytologic fine-needle aspirates must be utilized and triaged judiciously to achieve both objectives. In this review, strategies in utilizing fine-needle aspirates will be discussed in the context of our current understanding of the clinically actionable molecular aberrations underlying non-small cell lung cancer and the molecular assays applied to these samples in order to obtain treatment-relevant molecular diagnostic information.

No MeSH data available.


Related in: MedlinePlus

Example case of anaplastic lymphoma kinase (ALK) rearrangement fluorescence in-situ hybridization assay performed on a direct smear containing lung adenocarcinoma cells. The arrows point to the split orange and green signals that are separated by a distance of > 2 signal diameters. These nuclei would be scored as positive for the ALK rearrangement.
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f3-jptm-49-4-300: Example case of anaplastic lymphoma kinase (ALK) rearrangement fluorescence in-situ hybridization assay performed on a direct smear containing lung adenocarcinoma cells. The arrows point to the split orange and green signals that are separated by a distance of > 2 signal diameters. These nuclei would be scored as positive for the ALK rearrangement.

Mentions: FISH is currently the preferred approach to assaying lung adenocarcinomas for ALK rearrangements according to expert recommendations based on review of the literature [10]. In the United States of America, there is only one test approved by the Food and Drug Administration (FDA) for this purpose. This assay utilizes a dual ALK breakapart probe strategy in which orange and green labeled probes hybridize to the highly conserved translocation breakpoint region in the ALK gene. ALK gene loci that have not undergone rearrangement typically display fused orange and green signals (yellow) or juxtaposed touching orange and green signals. When an ALK rearrangement occurs, the orange and green signals become separated. However, as the majority of the ALK rearrangements involve a small inversion within chromosome 2p, rather than a rearrangement involving another chromosome, the extent to which the two signals are split is finite. In order to score a nucleus as positive for the ALK rearrangement, the orange and green signals must be separated by a distance of >2 signal diameters (Fig. 3); a nucleus can also be scored positive if a single orange signal without a corresponding green signal is observed [53]. Typically, up to 100 tumor cell nuclei are scored in this assay and a lung adenocarcinoma is considered positive for the ALK rearrangement if at least 15% of the nuclei are scored as positive for the rearrangement [53,54].


The Utilization of Cytologic Fine-Needle Aspirates of Lung Cancer for Molecular Diagnostic Testing.

Roh MH - J Pathol Transl Med (2015)

Example case of anaplastic lymphoma kinase (ALK) rearrangement fluorescence in-situ hybridization assay performed on a direct smear containing lung adenocarcinoma cells. The arrows point to the split orange and green signals that are separated by a distance of > 2 signal diameters. These nuclei would be scored as positive for the ALK rearrangement.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4508567&req=5

f3-jptm-49-4-300: Example case of anaplastic lymphoma kinase (ALK) rearrangement fluorescence in-situ hybridization assay performed on a direct smear containing lung adenocarcinoma cells. The arrows point to the split orange and green signals that are separated by a distance of > 2 signal diameters. These nuclei would be scored as positive for the ALK rearrangement.
Mentions: FISH is currently the preferred approach to assaying lung adenocarcinomas for ALK rearrangements according to expert recommendations based on review of the literature [10]. In the United States of America, there is only one test approved by the Food and Drug Administration (FDA) for this purpose. This assay utilizes a dual ALK breakapart probe strategy in which orange and green labeled probes hybridize to the highly conserved translocation breakpoint region in the ALK gene. ALK gene loci that have not undergone rearrangement typically display fused orange and green signals (yellow) or juxtaposed touching orange and green signals. When an ALK rearrangement occurs, the orange and green signals become separated. However, as the majority of the ALK rearrangements involve a small inversion within chromosome 2p, rather than a rearrangement involving another chromosome, the extent to which the two signals are split is finite. In order to score a nucleus as positive for the ALK rearrangement, the orange and green signals must be separated by a distance of >2 signal diameters (Fig. 3); a nucleus can also be scored positive if a single orange signal without a corresponding green signal is observed [53]. Typically, up to 100 tumor cell nuclei are scored in this assay and a lung adenocarcinoma is considered positive for the ALK rearrangement if at least 15% of the nuclei are scored as positive for the rearrangement [53,54].

Bottom Line: In this era of precision medicine, our understanding and knowledge of the molecular landscape associated with lung cancer pathogenesis continues to evolve.During the management of these patients, minimally invasive procedures to obtain samples for tissue diagnoses are desirable.Thus, cytologic fine-needle aspirates must be utilized and triaged judiciously to achieve both objectives.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA.

ABSTRACT
In this era of precision medicine, our understanding and knowledge of the molecular landscape associated with lung cancer pathogenesis continues to evolve. This information is being increasingly exploited to treat advanced stage lung cancer patients with tailored, targeted therapy. During the management of these patients, minimally invasive procedures to obtain samples for tissue diagnoses are desirable. Cytologic fine-needle aspirates are often utilized for this purpose and are important not only for rendering diagnoses to subtype patients' lung cancers, but also for ascertaining molecular diagnostic information for treatment purposes. Thus, cytologic fine-needle aspirates must be utilized and triaged judiciously to achieve both objectives. In this review, strategies in utilizing fine-needle aspirates will be discussed in the context of our current understanding of the clinically actionable molecular aberrations underlying non-small cell lung cancer and the molecular assays applied to these samples in order to obtain treatment-relevant molecular diagnostic information.

No MeSH data available.


Related in: MedlinePlus