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Synergistic Effect of Bcl-2 and Cyclin A2 on Adverse Recurrence-Free Survival in Stage I Non-small Cell Lung Cancer

Annals of Surgical Oncology Aims and scope Submit manuscript

ABSTRACT

Background

The prognostic significance of cyclin A2 overexpression in non-small cell lung cancer (NSCLC) is controversial.

Methods

To understand the effect of cyclin A2 on recurrence in NSCLC, we retrospectively analyzed the expression of Bcl-2, cyclin A2, E-cadherin, Ki-67, and p53 using immunohistochemistry in 635 NSCLCs.

Results

Overexpression of cyclin A2 was found in 466 (73 %) of 635 NSCLCs, and recurrence occurred in 291 (46 %) of 635 NSCLCs with a median follow-up of 5.4 years. The relationship between recurrence and cyclin A2 overexpression was not homogenous by pathologic stage (Breslow–Day test for homogeneity, P = 0.007). Overexpression of cyclin A2 was associated with poor recurrence-free survival (RFS) in 374 stage I NSCLCs (P = 0.02), and RFS was worse in patient with negative expression of Bcl-2 than those with positive expression of Bcl-2. Cox proportional hazard analysis showed that stage I NSCLC patients with overexpression of cyclin A2 and negative expression of Bcl-2 had poorer RFS (hazard ratio = 3.86, 95 % confidence interval = 1.07–15.77; P = 0.03) than those with normal expression of cyclin A2 and Bcl-2, after adjusting for age, adjuvant radiotherapy, and histology. Neural network and generalized linear model including cyclin A2 and Bcl-2 showed best performance in the prediction of recurrence; error rates for neural network and generalized linear model were 15 % and 12 %, respectively.

Conclusions

Negative effect of cyclin A2 on RFS in stage I NSCLC was aggravated by negative expression of Bcl-2.

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ACKNOWLEDGMENT

The authors wish to thank Eun-Kyung Kim and Jin-Hee Lee for data collection and management, and Hoon Suh and Seo Kyu Park for sample collection. This work was supported by grants from the Korea Healthcare technology R & D project, Ministry of Health & Welfare (A101148), and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2011-0029138), Republic of Korea.

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Authors and Affiliations

  1. Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, South Korea

    Eunkyung Ko MD, PhD, Yujin Kim MD, PhD, Joobae Park MD, PhD & Duk-Hwan Kim MD, PhD

  2. Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Eun Yoon Cho MD, PhD & Jungho Han MD, PhD

  3. Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Young Mog Shim MD, PhD

  4. Samsung Biomedical Research Institute, Seoul, South Korea

    Duk-Hwan Kim MD, PhD

Authors
  1. Eunkyung Ko MD, PhD
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  2. Yujin Kim MD, PhD
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  3. Eun Yoon Cho MD, PhD
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  4. Jungho Han MD, PhD
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  5. Young Mog Shim MD, PhD
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  6. Joobae Park MD, PhD
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  7. Duk-Hwan Kim MD, PhD
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Correspondence to Duk-Hwan Kim MD, PhD.

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Ko, E., Kim, Y., Cho, E.Y. et al. Synergistic Effect of Bcl-2 and Cyclin A2 on Adverse Recurrence-Free Survival in Stage I Non-small Cell Lung Cancer. Ann Surg Oncol 20, 1005–1012 (2013). https://doi.org/10.1245/s10434-012-2727-2

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  • DOI: https://doi.org/10.1245/s10434-012-2727-2

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