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A cohort study of cyclin D1 expression and prognosis in 602 colon cancer cases

Shuji Ogino1, Katsuhiko Nosho, Natsumi Irahara

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, USA. shuji_ogino@dfci.harvard.edu

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|June 25, 2009
PubMed
Abstract

Insights

Cyclin D1 overexpression in colon cancer is linked to better patient survival. This finding holds true even when considering other molecular factors like microsatellite instability.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Cyclin D1 and cyclin-dependent kinases (CDKs) are frequently activated in colorectal cancer.
  • CDK inhibitors like p27 (CDKN1B) and p21 (CDKN1A) can block cyclin D1 activity.
  • The prognostic value of tumoral cyclin D1 is uncertain, with limited understanding of its interaction with other molecular markers.

Purpose of the Study:

  • To investigate the prognostic significance of tumoral cyclin D1 overexpression in colon cancer.
  • To assess the impact of cyclin D1 on patient survival, considering potential confounding factors.
  • To explore the interplay between cyclin D1, p53, p21, p27, and molecular events like microsatellite instability (MSI).

Main Methods:

  • Analysis of 602 colon cancer patients (stage I-IV) from two prospective cohorts.
  • Immunohistochemistry used to detect cyclin D1 overexpression in 330 (55%) tumors.
  • Cox proportional hazard models employed to calculate hazard ratios for cancer-specific and overall mortality, adjusted for numerous molecular and clinical features.

Main Results:

  • Cyclin D1 overexpression was associated with significantly lower cancer-specific mortality (adjusted HR, 0.57; P = 0.0048) and overall mortality (adjusted HR, 0.74; P = 0.036).
  • Kaplan-Meier analysis and univariate/multivariate Cox regression confirmed this association.
  • A significant interaction between cyclin D1 and MSI status was observed, suggesting differential survival effects based on MSI-high or MSI-low/microsatellite-stable tumors.

Conclusions:

  • Cyclin D1 overexpression is a favorable prognostic marker in colon cancer, indicating longer patient survival.
  • The prognostic impact of cyclin D1 may be modulated by the tumor's microsatellite instability status.
  • Further research into the molecular mechanisms underlying this association is warranted.

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