Histopathologic and cytogenetic features of pulmonary adenoid cystic carcinoma

Anja Roden, Patricia T Greipp, Darlene L. Knutson, Sara M. Kloft-Nelson, Sarah M. Jenkins, Randolph Stuart Marks, Marie Christine Aubry, Joaquín J. García

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Introduction: A significant portion of adenoid cystic carcinoma (ACC) cases are characterized by a t(6;9)(q22-23;p23-24) translocation that originates a MYB-NFIB fusion oncogene. The MYB-NFIB fusion oncoprotein activates transcription of MYB-mediated pathways that impact cell cycle control, DNA repair, and apoptosis. This translocation seems highly specific for ACC. Moreover, therapies targeting MYB-activated pathways to treat ACC are being explored. Pulmonary ACC (PACC) has not been thoroughly studied for rearrangements of the MYB gene. Methods: Mayo Clinic Rochester surgical pathology archives (1972-2011) were searched for PACC. All cases were reviewed and classified according to the predominant histologic pattern (cribriform, solid, and tubular) by two surgical pathologists. Fluorescence in situ hybridization (FISH) was employed using a break-apart strategy to detect MYB rearrangement (at 6q23.3). Medical records were studied. Results: Forty cases of PACC were studied; tissue blocks were available for FISH analysis in 35 cases. Six cases failed to hybridize. In 12 of 29 cases (41%), the MYB gene region was disrupted, whereas 17 cases (59%) showed no evidence of rearrangement. FISH studies performed on other histologic subtypes of lung cancer (10 squamous cell carcinomas, 10 adenocarcinomas, and 10 small-cell carcinomas) failed to show MYB rearrangement. There was no significant difference in MYB rearrangement status with respect to predominant histologic pattern, clinical features, or clinical outcome. Conclusions: A MYB rearrangement was identified in 41% of PACC and was 100% specific. FISH studies for MYB may be of diagnostic utility in PACC, particularly on small biopsy specimens. MYB rearrangement in PACC does not seem to be associated with clinical features or prognosis.

Original languageEnglish (US)
Pages (from-to)1570-1575
Number of pages6
JournalJournal of Thoracic Oncology
Volume10
Issue number11
DOIs
StatePublished - Nov 1 2015

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Adenoid Cystic Carcinoma
Cytogenetics
Fluorescence In Situ Hybridization
Lung
Oncogene Fusion
Surgical Pathology
Small Cell Carcinoma
Gene Rearrangement
Oncogene Proteins
Cell Cycle Checkpoints
DNA Repair
Medical Records
Squamous Cell Carcinoma
Lung Neoplasms
Adenocarcinoma
Apoptosis
Biopsy
Genes

Keywords

  • Fluorescence in situ hybridization
  • MYB rearrangement
  • MYB-NFIB fusion
  • Pulmonary adenoid cystic carcinoma
  • t(6;9)

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Histopathologic and cytogenetic features of pulmonary adenoid cystic carcinoma. / Roden, Anja; Greipp, Patricia T; Knutson, Darlene L.; Kloft-Nelson, Sara M.; Jenkins, Sarah M.; Marks, Randolph Stuart; Aubry, Marie Christine; García, Joaquín J.

In: Journal of Thoracic Oncology, Vol. 10, No. 11, 01.11.2015, p. 1570-1575.

Research output: Contribution to journalArticle

Roden, Anja ; Greipp, Patricia T ; Knutson, Darlene L. ; Kloft-Nelson, Sara M. ; Jenkins, Sarah M. ; Marks, Randolph Stuart ; Aubry, Marie Christine ; García, Joaquín J. / Histopathologic and cytogenetic features of pulmonary adenoid cystic carcinoma. In: Journal of Thoracic Oncology. 2015 ; Vol. 10, No. 11. pp. 1570-1575.
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abstract = "Introduction: A significant portion of adenoid cystic carcinoma (ACC) cases are characterized by a t(6;9)(q22-23;p23-24) translocation that originates a MYB-NFIB fusion oncogene. The MYB-NFIB fusion oncoprotein activates transcription of MYB-mediated pathways that impact cell cycle control, DNA repair, and apoptosis. This translocation seems highly specific for ACC. Moreover, therapies targeting MYB-activated pathways to treat ACC are being explored. Pulmonary ACC (PACC) has not been thoroughly studied for rearrangements of the MYB gene. Methods: Mayo Clinic Rochester surgical pathology archives (1972-2011) were searched for PACC. All cases were reviewed and classified according to the predominant histologic pattern (cribriform, solid, and tubular) by two surgical pathologists. Fluorescence in situ hybridization (FISH) was employed using a break-apart strategy to detect MYB rearrangement (at 6q23.3). Medical records were studied. Results: Forty cases of PACC were studied; tissue blocks were available for FISH analysis in 35 cases. Six cases failed to hybridize. In 12 of 29 cases (41{\%}), the MYB gene region was disrupted, whereas 17 cases (59{\%}) showed no evidence of rearrangement. FISH studies performed on other histologic subtypes of lung cancer (10 squamous cell carcinomas, 10 adenocarcinomas, and 10 small-cell carcinomas) failed to show MYB rearrangement. There was no significant difference in MYB rearrangement status with respect to predominant histologic pattern, clinical features, or clinical outcome. Conclusions: A MYB rearrangement was identified in 41{\%} of PACC and was 100{\%} specific. FISH studies for MYB may be of diagnostic utility in PACC, particularly on small biopsy specimens. MYB rearrangement in PACC does not seem to be associated with clinical features or prognosis.",
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T1 - Histopathologic and cytogenetic features of pulmonary adenoid cystic carcinoma

AU - Roden, Anja

AU - Greipp, Patricia T

AU - Knutson, Darlene L.

AU - Kloft-Nelson, Sara M.

AU - Jenkins, Sarah M.

AU - Marks, Randolph Stuart

AU - Aubry, Marie Christine

AU - García, Joaquín J.

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