Molecular alterations associated with cyclin d1 overexpression in endometrial cancer

Gema Moreno‐Bueno; Sandra Rodríguez‐Perales; Carolina Sánchez‐Estévez; Raquel Marcos; David Hardisson; Juan C. Cigudosa; José Palacios

doi:10.1002/ijc.20130

journal article Feb 19, 2004

Molecular alterations associated with cyclin d1 overexpression in endometrial cancer

Gema Moreno‐Bueno Sandra Rodríguez‐Perales Carolina Sánchez‐Estévez Raquel Marcos David Hardisson

Juan C. Cigudosa José Palacios

International Journal of Cancer Vol. 110 No. 2 pp. 194-200 · Wiley

View at Publisher Save 10.1002/ijc.20130

Abstract

AbstractCyclin D1 is frequently overexpressed in human neoplasias by gene rearrangement and amplification. In addition, Ras, PTEN and β‐catenin appear to modulate cyclin D1 levels. Since the causes of cyclin D1 overexpression are poorly understood in EC, we investigated whether or not this alteration is due to cyclin D1 gene amplification or to RAS, PTEN and β‐catenin mutation. We analyzed cyclin D1 expression in 18 AEHs, 65 EECs and 27 NEECs by immunohistochemistry as well as CCND1 gene amplification by FISH. In EECs, mutations in K‐RAS, PTEN, β‐catenin and CCND1 were studied by PCR‐SSCP and sequencing and MSI was evaluated by analyzing BAT‐25 and BAT‐26 microsatellites. Contingency tests were used to evaluate the relationships between variables. Cyclin D1 overexpression was not observed in AEHs but was present in 13.8% of EECs and 11.2% of NEECs (p = 0.031). CCND1 amplification was more frequent in NEECs (26.3%) than in EECs (2.1%) (p = 0.002). In EECs, cyclin D1 overexpression was not associated with mutations in K‐RAS, PTEN or β‐catenin. However, in EECs with β‐catenin mutations, cyclin D1 was expressed mainly by cells expressing β‐catenin in the cytoplasm and nucleus but not in those with membranous expression. Finally, cyclin D1 overexpression was associated with MSI (p = 0.047). The molecular alterations associated with cyclin D1 overexpression differ in the 2 clinicopathologic types of EC. Cyclin D1 overexpression is associated with gene amplification in NEECs and with nucleocytoplasmic expression of β‐catenin and MSI in EECs. © 2004 Wiley‐Liss, Inc.

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Metrics

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Citations

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References

Details

Published: Feb 19, 2004
Vol/Issue: 110(2)
Pages: 194-200
License: View

Authors

G

Gema Moreno‐Bueno

S

Sandra Rodríguez‐Perales

C

Carolina Sánchez‐Estévez

Ramón y Cajal Health Research Institute; CIBER-ONC, Carlos III Health Institute; Department of Pathology, Hospital Ramón y Cajal; Faculty of Medicine, Alcalá University, Madrid

Funding

Fundación Inocente Inocente-Spain Award: PI020355

Cite This Article

Gema Moreno‐Bueno, Sandra Rodríguez‐Perales, Carolina Sánchez‐Estévez, et al. (2004). Molecular alterations associated with cyclin d1 overexpression in endometrial cancer. International Journal of Cancer, 110(2), 194-200. https://doi.org/10.1002/ijc.20130

Molecular alterations associated with cyclin d1 overexpression in endometrial cancer

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