Common Fluorescence In Situ Hybridization Applications in Cytology

Our plain-English summary of Common Fluorescence In Situ Hybridization Applications in Cytology, by S. Savic, L. Bubendorf (Archives of Pathology & Laboratory Medicine, 2016).

The study

• Authors: S. Savic, L. Bubendorf
• Journal: Archives of Pathology & Laboratory Medicine
• Published: 2016;140(12):1323-1330
• Type of article: Review
• Cited by: 29 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Context: - Fluorescence in situ hybridization (FISH) is a well-established method for detection of genomic aberrations in diagnostic, prognostic, and predictive marker testing.

Objective: - To review common applications of FISH in cytology.

Data Sources: - The published literature was reviewed.

Conclusions: - Cytology is particularly well suited for all kinds of FISH applications, which is highlighted in respiratory tract cytology with an increasing demand for predictive FISH testing in lung cancer. Fluorescence in situ hybridization is the gold standard for detection of predictive anaplastic lymphoma kinase gene (ALK) rearrangements, and the same evaluation criteria as in histology apply to cytology. Several other gene rearrangements, including ROS proto-oncogene 1 receptor tyrosine kinase (ROS1), are becoming clinically important and share the same underlining cytogenetic mechanisms with ALK. MET amplification is one of the most common mechanisms of acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and can be targeted by crizotinib. As genomic aberrations are a hallmark of malignant cells, FISH is a valuable objective ancillary diagnostic tool. In urinary tract cytology, atypical urothelial cells equivocal for malignancy are a common diagnostic dilemma and multitarget FISH can help clarify such cells. Diagnosis of malignant mesothelioma remains one of the most challenging fields in effusion cytology, and ancillary FISH is useful in establishing the diagnosis. Fluorescence in situ hybridization is a morphology-based technique, and the prerequisite for reliable FISH results is a targeted evaluation of the cells in question (eg, cancer or atypical cells). Cytopathologists and cytotechnicians should therefore be involved in molecular testing in order to select the best material and to provide their morphologic expertise.

In plain English

This was a review of published literature on fluorescence in situ hybridization (FISH), a laboratory test that detects chromosome changes in cells collected for cytology. It covered lung cancer, urinary tract cytology and malignant mesothelioma in fluid samples (effusions). Asbestos is not discussed. The authors noted that reported sensitivities of cytology for mesothelioma range from 32% to 76%. They described their own earlier retrospective, multicenter study of 52 pleural effusions from patients with biopsy-proven malignant mesothelioma. In that study the UroVysion FISH test had an overall sensitivity of 79% and a positive predictive value of 100%. A 9p21 deletion was present in 38 of 40 FISH-positive effusions, and none of 28 benign control effusions showed chromosomal aberrations. The authors reported that homozygous 9p21 loss occurs in only 25% of peritoneal mesotheliomas. The authors concluded that FISH detecting 9p21 deletion is a powerful ancillary tool allowing a definitive mesothelioma diagnosis in effusion cytology when radiologic findings are appropriate. They noted that many clinicians demand histologic (tissue) confirmation, which mesothelioma pathology expert panels also advocate.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review article of published literature on common uses of FISH in cytology
• Who was studied: Published literature on FISH testing of cytology specimens from lung cancer, urinary tract and effusions (including malignant mesothelioma); no new patient group was studied
• Exposure: No exposure was studied. The review concerns a laboratory test (FISH) on cytology specimens; asbestos and fiber types are not mentioned.
• Main results:
  • The authors' earlier study, of 52 conventional pleural effusions from patients with biopsy-proven malignant mesothelioma, found that UroVysion FISH had an overall sensitivity of 79% and a positive predictive value of 100%
  • In that earlier study, 9p21 deletion was present in 95% (38 of 40) of the FISH-positive effusions
  • In that earlier study, none of the 28 control specimens from patients with benign effusions showed chromosomal aberrations by FISH
  • Other studies, which counted only homozygous 9p21 deletion as positive, reported sensitivities of 56% to 74% for mesothelioma
  • In peritoneal mesotheliomas, homozygous 9p21 loss is reported in only 25%
  • Reported sensitivities of cytology for diagnosing malignant mesothelioma range from 32% to 76%
  • In the authors' earlier series of 143 non-small cell lung cancers tested on routine cytology specimens, there were no ALK FISH hybridization failures
• The authors' conclusion: The authors concluded that FISH detecting 9p21 deletion is a powerful ancillary tool that allows a definitive diagnosis of malignant mesothelioma in effusion cytology when radiologic findings are appropriate
• Limitations the authors state:
  • A definitive mesothelioma diagnosis from cytology alone is rarely accepted; many clinicians demand histologic confirmation, and mesothelioma pathology expert panels also advocate it
  • For ALK testing in lung cancer, false-positive FISH rates above 10% have been reported

Topics

Medical terms in this study, explained in our Lexicon: Fluorescence In Situ Hybridization (FISH), Cytology, Lung Cancer, Histology, ROS1, EGFR, Tyrosine Kinase Inhibitor, Malignant Mesothelioma.

Related studies

• Fluorescence in situ hybridization in the definitive diagnosis of malignant mesothelioma in effusion cytology — S. Savic, N. Franco, et al. (2010)
• Fluorescence in situ hybridization detection of chromosome 22 monosomy in pleural effusion cytology for the diagnosis of mesothelioma — Y. Kinoshita, M. Hamasaki, et al. (2021)
• Evaluation of RET Gene Rearrangement by Fluorescence In Situ Hybridization in Malignant Mesothelioma — S. Salvi, J.L. Ravetti, et al. (2018)
• Hemizygous loss of NF2 detected by fluorescence in situ hybridization is useful for the diagnosis of malignant pleural mesothelioma — Y. Kinoshita, M. Hamasaki, et al. (2020)
• The potential value of comparative genomic hybridization analysis in effusion-and fine needle aspiration cytology — H. Nagel, H.J. Schulten, et al. (2002)
• MTAP immunohistochemistry is an accurate and reproducible surrogate for CDKN2A fluorescence in situ hybridization in diagnosis of malignant pleural mesothelioma — D.B. Chapel, J.J. Schulte, et al. (2020)

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