The use of CDKN2A deletion as a diagnostic marker for malignant mesothelioma in body cavity effusions

Peter B Illei, Marc Ladanyi, Valerie W. Rusch, Maureen F. Zakowski

Research output: Contribution to journalArticle

Abstract

BACKGROUND. The distinction between benign reactive mesothelial cells and malignant mesothelial cells in serous effusions is difficult and has an unusually high false negative rate. Unfortunately, there are no generally accepted markers to distinguish between benign reactive and malignant mesothelial cells. Homozygous deletion of CDKN2A is frequent in mesothelioma (present in > 70% of tumors). Therefore, detection of CDKN2A deletion by fluorescence in situ hybridization (FISH) was evaluated as an ancillary test in the cytologic diagnosis of malignant mesothelioma. METHODS. Dual-color FISH for CDKN2A and chromosome 9 centromere was performed on cytolyt-fixed Thinprep slides from 6 cytologically suspicious and 7 cytologically positive effusions (all with histologically confirmed mesothelioma) and in 19 cytologically benign effusions (14 pleural effusions, 3 pericardial effusions, and 2 abdominal fluid specimens). Specimens containing ≥ 15 nuclei that lacked signals for CDKN2A but showed at least 1 signal for chromosome 9 centromere were considered positive. In samples with negative cytology, the nuclei of at least 100 mesothelial cells were evaluated; whereas, in specimens with positive or suspicious cytology, counting nuclei was done only if <15% of nuclei showed homozygous loss of CDKN2A. RESULTS. Homozygous deletion was detected in mesothelial cells in six of seven specimens with positive cytology and in six of six specimens with suspicious cytology. Cytologically, there were numerous tumor cells in a single positive specimen without homozygous deletion. All 19 cytologically negative specimens were negative for CDKN2A deletion. CONCLUSIONS. The detection of homozygous CDKN2A deletion by FISH would have been helpful in confirming a diagnosis of mesothelioma over reactive mesothelial cells in 12 of 13 samples with positive or suspicious cytology. Further studies on larger series of patients with suspicious cytology are needed to evaluate the validity and efficiency of this approach for improving the diagnostic accuracy of effusion cytology.

Original languageEnglish (US)
Pages (from-to)51-56
Number of pages6
JournalCancer
Volume99
Issue number1
DOIs
StatePublished - Feb 25 2003
Externally publishedYes

Fingerprint

Cell Biology
Mesothelioma
Fluorescence In Situ Hybridization
Chromosomes, Human, Pair 9
Centromere
Pericardial Effusion
Pleural Effusion
Malignant Mesothelioma
Neoplasms
Color

Keywords

  • CDKN2A
  • Chromosome 9
  • Effusions
  • Fluorescent in situ hybridization
  • Mesothelioma
  • Reactive mesothelium
  • Sensitivity

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

The use of CDKN2A deletion as a diagnostic marker for malignant mesothelioma in body cavity effusions. / Illei, Peter B; Ladanyi, Marc; Rusch, Valerie W.; Zakowski, Maureen F.

In: Cancer, Vol. 99, No. 1, 25.02.2003, p. 51-56.

Research output: Contribution to journalArticle

Illei, Peter B ; Ladanyi, Marc ; Rusch, Valerie W. ; Zakowski, Maureen F. / The use of CDKN2A deletion as a diagnostic marker for malignant mesothelioma in body cavity effusions. In: Cancer. 2003 ; Vol. 99, No. 1. pp. 51-56.
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abstract = "BACKGROUND. The distinction between benign reactive mesothelial cells and malignant mesothelial cells in serous effusions is difficult and has an unusually high false negative rate. Unfortunately, there are no generally accepted markers to distinguish between benign reactive and malignant mesothelial cells. Homozygous deletion of CDKN2A is frequent in mesothelioma (present in > 70{\%} of tumors). Therefore, detection of CDKN2A deletion by fluorescence in situ hybridization (FISH) was evaluated as an ancillary test in the cytologic diagnosis of malignant mesothelioma. METHODS. Dual-color FISH for CDKN2A and chromosome 9 centromere was performed on cytolyt-fixed Thinprep slides from 6 cytologically suspicious and 7 cytologically positive effusions (all with histologically confirmed mesothelioma) and in 19 cytologically benign effusions (14 pleural effusions, 3 pericardial effusions, and 2 abdominal fluid specimens). Specimens containing ≥ 15 nuclei that lacked signals for CDKN2A but showed at least 1 signal for chromosome 9 centromere were considered positive. In samples with negative cytology, the nuclei of at least 100 mesothelial cells were evaluated; whereas, in specimens with positive or suspicious cytology, counting nuclei was done only if <15{\%} of nuclei showed homozygous loss of CDKN2A. RESULTS. Homozygous deletion was detected in mesothelial cells in six of seven specimens with positive cytology and in six of six specimens with suspicious cytology. Cytologically, there were numerous tumor cells in a single positive specimen without homozygous deletion. All 19 cytologically negative specimens were negative for CDKN2A deletion. CONCLUSIONS. The detection of homozygous CDKN2A deletion by FISH would have been helpful in confirming a diagnosis of mesothelioma over reactive mesothelial cells in 12 of 13 samples with positive or suspicious cytology. Further studies on larger series of patients with suspicious cytology are needed to evaluate the validity and efficiency of this approach for improving the diagnostic accuracy of effusion cytology.",
keywords = "CDKN2A, Chromosome 9, Effusions, Fluorescent in situ hybridization, Mesothelioma, Reactive mesothelium, Sensitivity",
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T1 - The use of CDKN2A deletion as a diagnostic marker for malignant mesothelioma in body cavity effusions

AU - Illei, Peter B

AU - Ladanyi, Marc

AU - Rusch, Valerie W.

AU - Zakowski, Maureen F.

PY - 2003/2/25

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N2 - BACKGROUND. The distinction between benign reactive mesothelial cells and malignant mesothelial cells in serous effusions is difficult and has an unusually high false negative rate. Unfortunately, there are no generally accepted markers to distinguish between benign reactive and malignant mesothelial cells. Homozygous deletion of CDKN2A is frequent in mesothelioma (present in > 70% of tumors). Therefore, detection of CDKN2A deletion by fluorescence in situ hybridization (FISH) was evaluated as an ancillary test in the cytologic diagnosis of malignant mesothelioma. METHODS. Dual-color FISH for CDKN2A and chromosome 9 centromere was performed on cytolyt-fixed Thinprep slides from 6 cytologically suspicious and 7 cytologically positive effusions (all with histologically confirmed mesothelioma) and in 19 cytologically benign effusions (14 pleural effusions, 3 pericardial effusions, and 2 abdominal fluid specimens). Specimens containing ≥ 15 nuclei that lacked signals for CDKN2A but showed at least 1 signal for chromosome 9 centromere were considered positive. In samples with negative cytology, the nuclei of at least 100 mesothelial cells were evaluated; whereas, in specimens with positive or suspicious cytology, counting nuclei was done only if <15% of nuclei showed homozygous loss of CDKN2A. RESULTS. Homozygous deletion was detected in mesothelial cells in six of seven specimens with positive cytology and in six of six specimens with suspicious cytology. Cytologically, there were numerous tumor cells in a single positive specimen without homozygous deletion. All 19 cytologically negative specimens were negative for CDKN2A deletion. CONCLUSIONS. The detection of homozygous CDKN2A deletion by FISH would have been helpful in confirming a diagnosis of mesothelioma over reactive mesothelial cells in 12 of 13 samples with positive or suspicious cytology. Further studies on larger series of patients with suspicious cytology are needed to evaluate the validity and efficiency of this approach for improving the diagnostic accuracy of effusion cytology.

AB - BACKGROUND. The distinction between benign reactive mesothelial cells and malignant mesothelial cells in serous effusions is difficult and has an unusually high false negative rate. Unfortunately, there are no generally accepted markers to distinguish between benign reactive and malignant mesothelial cells. Homozygous deletion of CDKN2A is frequent in mesothelioma (present in > 70% of tumors). Therefore, detection of CDKN2A deletion by fluorescence in situ hybridization (FISH) was evaluated as an ancillary test in the cytologic diagnosis of malignant mesothelioma. METHODS. Dual-color FISH for CDKN2A and chromosome 9 centromere was performed on cytolyt-fixed Thinprep slides from 6 cytologically suspicious and 7 cytologically positive effusions (all with histologically confirmed mesothelioma) and in 19 cytologically benign effusions (14 pleural effusions, 3 pericardial effusions, and 2 abdominal fluid specimens). Specimens containing ≥ 15 nuclei that lacked signals for CDKN2A but showed at least 1 signal for chromosome 9 centromere were considered positive. In samples with negative cytology, the nuclei of at least 100 mesothelial cells were evaluated; whereas, in specimens with positive or suspicious cytology, counting nuclei was done only if <15% of nuclei showed homozygous loss of CDKN2A. RESULTS. Homozygous deletion was detected in mesothelial cells in six of seven specimens with positive cytology and in six of six specimens with suspicious cytology. Cytologically, there were numerous tumor cells in a single positive specimen without homozygous deletion. All 19 cytologically negative specimens were negative for CDKN2A deletion. CONCLUSIONS. The detection of homozygous CDKN2A deletion by FISH would have been helpful in confirming a diagnosis of mesothelioma over reactive mesothelial cells in 12 of 13 samples with positive or suspicious cytology. Further studies on larger series of patients with suspicious cytology are needed to evaluate the validity and efficiency of this approach for improving the diagnostic accuracy of effusion cytology.

KW - CDKN2A

KW - Chromosome 9

KW - Effusions

KW - Fluorescent in situ hybridization

KW - Mesothelioma

KW - Reactive mesothelium

KW - Sensitivity

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