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

Department of Pathology, University Medical Centre, Utrecht, The Netherlands.
Journal of clinical pathology (Impact Factor: 2.92). 04/2008; 61(3):311-6. DOI: 10.1136/jcp.2006.042648
Source: PubMed


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.
To assess their presence in early-onset gastric cancer (EOGC), stump cancers and conventional gastric cancers and ascertain how they influence survival in EOGC.
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.
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.
EOGCs have a unique molecular phenotype and LMW isoforms of cyclin E may independently influence survival in EOGC.

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    • "It has been shown that over-expression of cyclin E is associated with tumor progression and that high levels of total or processed cyclin E strongly predicts poor prognosis of breast cancer patients [3] [4] [5]. Moreover, truncated cyclin E is also observed in other kinds of tumors and is indicative of poor survival [6] [7] [8]. Recently, it is shown that resistance to letrozole in breast cancer is due to overexpression of proteolyzed cyclin E [9]. "
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    Preview · Article · Mar 2012 · FEBS letters
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    • "The present study reports frequencies in the lower range, with EOGC having an even lower percentage of amplification (2%) and overexpression (0%) than late onset GC (8% and 7% respectively). Other studies have shown that EOGC have a different molecular expression profile than late onset GC [26, 27] which is consistent with the finding that these cancers show a different (lower) HER2 overexpression and amplification frequency than late onset GC. Other studies using whole slides have reported lower frequencies of overexpression as well [3, 38, 41]. "
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    ABSTRACT: ObjectiveThe aim of the study was to investigate the expression and significance of cyclin E in gastric carcinoma. MethodsWe detected the expression of cyclin E in three different pathologic types gastric carcinoma samples by immuno-histochemical staining technique (SP method). ResultsIn 59 gastric carcinoma samples the positive rate of cyclin E expression in gastric carcinoma was 55.93% (33/59), and it was significantly higher than that of normal gastric mucosa (10.53%, 2/19). The positive rates of cyclin E expression in poor differentiation group and mucoid carcinoma group were 68.75% (11/16) and 66.67% (16/24), respectively, and these were significantly higher than that in well-middle differentiation group (31.58%, 6/19), but there was no significant difference between the fronted two groups (P > 0.05). ConclusionThe high expression of cyclin E is associated with the progression of gastric carcinoma and probably related to the behavior of cellular biology. Key wordscyclin E-gastric carcinoma-expression
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