PTEN deletion is rare but often homogeneous in gastric cancer
- Sormeh Mina1,2,
- Benjamin A Bohn1,2,
- Ronald Simon1,
- Antje Krohn1,
- Matthias Reeh2,
- Dirk Arnold3,
- Carsten Bokemeyer4,
- Guido Sauter1,
- Jakob R Izbicki2,
- Andreas Marx1,
- Phillip R Stahl1
- 1Institute of Pathology, University Medical Center Hamburg–Eppendorf, Hamburg, Germany
- 2General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg–Eppendorf, Hamburg, Germany
- 3Hubertus Wald Tumor Center/University Cancer Center Hamburg (UCCH), University Medical Center Hamburg–Eppendorf, Hamburg, Germany
- 4Department of Internal Medicine II and Clinic (Oncology Center), University Medical Center Hamburg–Eppendorf, Hamburg, Germany
- Correspondence to Benjamin A Bohn, General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg–Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; b.bohn{at}uke.de
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Contributors All authors have read and approved the final version of the text. SM and BAB performed the analysis, analysed the data and prepared the manuscript. BAB is a guarantor. RS, AK, MR, DA, CB, JRI and AM devised the study and revised the manuscript. GS and PRS designed the study, interpreted the data and revised the manuscript critically. GS and PRS are guarantors.
- Accepted 16 April 2012
- Published Online First 25 May 2012
Abstract
Background and aim Gastric carcinoma is the second most frequent cause of cancer-related death worldwide. As PTEN is a potential modifier of tumour response to trastuzumab, a recently approved therapy in metastatic HER2 positive gastric cancer, the existence of PTEN deletions in primary gastric cancer was investigated.
Methods 230 primary gastric cancers were analysed in a tissue microarray format by dual labelling fluorescence in situ hybridisation for PTEN deletion. HER2 analysis was also performed. To study PTEN deletion heterogeneity, all available large tissue sections from primary cancer and corresponding metastases were analysed in seven patients.
Results Eight of 180 interpretable primary gastric cancer spots showed PTEN deletions (4.4%), including seven hemizygous and one homozygous deletion. PTEN deletion was correlated with nodal (8 of 122 cases (6.6%); p=0.041) and distant metastases (4 of 19 (21.1%); p<0.001). Large section validation showed a homogeneous distribution of PTEN deletion. HER2 positivity was seen in one PTEN deleted case.
Conclusion Genomic PTEN deletion is a rare event in gastric adenocarcinoma but correlates with metastatic disease. The homogeneous distribution pattern indicates that this alteration occurs early in tumour development.
- PTEN protein
- human
- gene deletion
- stomach neoplasms
- microarray analysis
- in Situ hybridisation
- fluorescence
- cancer research
- fish
- gut pathology
- gastroenterology
- cancer
- carcinoma
- chemotherapy
Footnotes
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SM and BAB have contributed equally to this work.
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Funding Financial support was provided by Werner Otto Stiftung, Hamburg.
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Competing interests None.
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Ethics approval Ethics approval was provided by the Ethics Committee of the Chamber of Physicians in Hamburg, Germany.
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Provenance and peer review Not commissioned; externally peer reviewed.
