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Cyclin E low molecular weight isoforms occur commonly in early-onset gastric cancer and independently predict survival

¹ Department of Pathology, University Medical Centre, Utrecht, The Netherlands
² Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
³ MRC Holland, Amsterdam, The Netherlands
⁴ Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands
⁵ Department of Neurogenetics, Academic Medical Centre, Amsterdam, The Netherlands

Correspondence to:
Dr Anya N A Milne, Pathology Dept H04.2.25, University Medical Centre Utrecht, Postbus 85500, 3508GA, Utrecht, The Netherlands; a.n.a.milne{at}umcutrecht.nl

Background: Post-translational cleavage of full-length cyclin E from the N-terminus can produce low molecular weight (LMW) isoforms of cyclin E containing the C-terminus only.

Aim: To assess their presence in early-onset gastric cancer (EOGC), stump cancers and conventional gastric cancers and ascertain how they influence survival in EOGC.

Methods: The expression of full-length and LMW isoforms of cyclin E in 330 gastric cancers, including early-onset gastric cancer (EOGC), stump cancer and conventional gastric cancer (>45 years old) was compared using antibodies targeted to the N- and C-terminals.

Results: LMW isoforms were found in 35% of EOGCs, compared to 8% of conventional gastric cancers and 4% of stump cancers; their presence was visualised in cell lines using western blot analysis. In addition, C-terminal staining was a positive predictor of survival in EOGC. In contrast, no correlation with survival was found with the N-terminal antibody which detects only full-length cyclin E.

Conclusion: EOGCs have a unique molecular phenotype and LMW isoforms of cyclin E may independently influence survival in EOGC.