Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

British Journal of Cancer
  • View all journals
  • Search
  • My Account Login
  • Content Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. british journal of cancer
  3. regular article
  4. article
Cyclin D1 overexpression is an indicator of poor prognosis in resectable non-small cell lung cancer
Download PDF
Download PDF
  • Regular Article
  • Open access
  • Published: 13 August 1999

Cyclin D1 overexpression is an indicator of poor prognosis in resectable non-small cell lung cancer

  • J S Keum1,
  • G Kong2,
  • S C Yang3,
  • D H Shin3,
  • S S Park3,
  • J H Lee3 &
  • …
  • J D Lee2 

British Journal of Cancer volume 81, pages 127–132 (1999)Cite this article

  • 2430 Accesses

  • 98 Citations

  • Metrics details

This article has been updated

Summary

Cyclin D1 is one of the G1 cyclins that control cell cycle progression by allowing G1 to S transition. Overexpression of cyclin D1 has been postulated to play an important role in the development of human cancers. We have investigated the correlation between cyclin D1 overexpression and known clinicopathological factors and also its prognostic implication on resected non-small-cell lung cancer (NSCLC) patients. Formalin-fixed and paraffin-embedded tumour tissues resected from 69 NSCLC patients between stages I and IIIa were immunohistochemically examined to detect altered cyclin D1 expression. Twenty-four cases (34.8%) revealed positive immunoreactivity for cyclin D1. Cyclin D1 overexpression is significantly higher in patients with lymph node metastasis (50.0% vs 14.4%, P = 0.002) and with advanced pathological stages (I, 10%; II, 53.8%; IIIa, 41.7%, P = 0.048; stage I vs II, IIIa, P = 0.006). Twenty-four patients with cyclin D1-positive immunoreactivity revealed a significantly shorter overall survival than the patients with negativity (24.0 ± 3.9 months vs 50.1 ± 6.4 months, P = 0.0299). Among 33 patients between stages I and II, nine patients with cyclin D1-positive immunoreactivity had a much shorter overall survival (29.7 ± 6.1 months vs 74.6 ± 8.6 months, P = 0.0066). These results suggest that cyclin D1 overexpression is involved in tumorigenesis of NSCLCs from early stage and could be a predictive molecular marker for poor prognosis in resectable NSCLC patients, which may help us to choose proper therapeutic modalities after resection of the tumor.

Similar content being viewed by others

A cyclin D1 intrinsically disordered domain accesses modified histone motifs to govern gene transcription

Article Open access 08 January 2024

Non-phosphorylatable cyclin D1 mutant potentiates endometrial hyperplasia and drives carcinoma with Pten loss

Article 24 February 2022

KIFC3 promotes the proliferation, migration and invasion of non-small cell lung cancer through the PI3K/AKT signaling pathway

Article Open access 03 September 2024

Article PDF

Change history

  • 16 November 2011

    This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication

References

  • Adelaide, J, Monges, G, Derderian, C, Seitz, JF & Birnbaum, D (1995). Oesophageal cancer and amplification of the human cyclin D gene CCND1/PRAD1. Br J Cancer 71: 64–68.

    Article  CAS  Google Scholar 

  • Åkervall, JA, Michalides, RJ, Mineta, H, Balm, A, Borg, Å, Dictor, MR, Jin, Y, Loftus, B, Mertens, F & Wennerberg, JP (1997). Amplification of cyclin D1 in squamous cell carcinoma of the head and neck and the prognostic value of chromosomal abnormalities and cyclin D1 overexpression. Cancer 79: 380–389.

    Article  Google Scholar 

  • Bartkova, J, Lukas, J, Strauss, M & Bartek, J (1994). Cell cycle-related variation and tissue-restricted expression of human cyclin D1 protein. J Pathol 172: 237–245.

    Article  CAS  Google Scholar 

  • Bartkova, J, Lukas, J, Strauss, M & Bartek, J (1995). Cyclin D1 oncoprotein aberrantly accumulates in malignancies of diverse histogenesis. Oncogene 10: 775–778.

    CAS  Google Scholar 

  • Betticher, DC, Heighway, J, Hasleton, PS, Altermatt, HJ, Ryder, WD, Cerny, T & Thatcher, N (1996). Prognostic significance of CCND1 (cyclin D1) overexpression in primary resected non-small-cell lung cancer. Br J Cancer 73: 294–300.

    Article  CAS  Google Scholar 

  • Callender, T, el-Naggar, AK, Lee, MS, Frankenthaler, R, Luna, MA & Batsakis, JG (1994). PRAD-1 (CCND1)/cyclin D1 oncogne amplification in primary head and neck squamous cell carcinoma. Cancer 74: 152–158.

    Article  CAS  Google Scholar 

  • Caputi, M, De Luca, L, Papaccio, G, D’Aponte, A, Cavallotti, I, Scala, P, Scarano, F, Manna, M, Gualdiero, L & De Luca, B (1997). Prognostic role of cyclin D1 in non small cell lung cancer: an immunohistochemical analysis. Eur J Histochem 41: 133–138.

    CAS  PubMed  Google Scholar 

  • de Vita, VT Jr, Hellman, S & Rosenberg, SA (1997). Cancer: Principles and Practices of Oncology. 5th edn, pp. 858–911 Lippincott: Philadelphia

    Google Scholar 

  • Fontanini, G, Vignati, S, Bigini, D, Mussi, A, Lucchi, M, Angeletti, CA, Basolo, F & Bevilacqua, G (1995). Bcl-2 protein: a prognostic factor inversely correlated to p53 in non-small cell lung cancer. Br J Cancer 71: 1003–1007.

    Article  CAS  Google Scholar 

  • Gillett, C, Fantl, V, Smith, R, Fisher, C, Bartek, J, Dickson, C, Barnes, D & Peters, G (1994). Amplification and overexpression of cyclin D1 in breast cancer detected by immunohistochemical staining. Cancer Res 54: 1812–1817.

    CAS  PubMed  Google Scholar 

  • Izbicki, JR, Passlick, B, Hosch, SB, Kubuschock, B, Schneider, C, Busch, C, Knoefel, WT, Thetter, O & Pantel, K (1996). Mode of spread in the early phase of lymphatic metastasis in non-small-cell lung cancer: significance of nodal micrometastasis. J Thorac Cardiovasc Surg 112: 623–630.

    Article  CAS  Google Scholar 

  • Jares, P, Fernandez, PL, Campo, E, Nadal, A, Bosch, F, Aiza, G, Nayach, I, Traserra, J & Cardesa, A (1994). PRAD-1/cyclin D1 gene amplification correlates with messenger RNA overexpression and tumor progression in human laryngeal carcinomas. Cancer Res 54: 4813–4817.

    CAS  PubMed  Google Scholar 

  • Jiang, W, Kahn, SM, Tomita, N, Zhang, YJ, Lu, SH & Weinstein, IB (1992). Amplification and expression of the human cyclin D gene in esophageal cancer. Cancer Res 52: 2980–2983.

    CAS  PubMed  Google Scholar 

  • Kastan, MB & Tooze, J (1997). Checkpoint Controls and Cancer. Cancer Surveys, Vol 29, pp. 7–24. Cold Spring Harbor Laboratory Press: New York

  • Kayser, K, Bulzebruk, H, Probst, G & Vogt-Moykopf, I (1987). Retrospective and prospective tumor staging evaluating prognostic factors in operated bronchus carcinoma patients. Cancer 59: 355–361.

    Article  CAS  Google Scholar 

  • Kern, JA, Schwartz, DA, Nordberg, JE, Weiner, DB, Greene, MI, Torney, L & Robinson, RA (1990). p185neu expression in human lung adenocarcinomas predicts shortened survival. Cancer Res 50: 5184–5187.

    CAS  PubMed  Google Scholar 

  • Kern, JA, Slebos, RJ, Top, B, Rodenhuis, S, Lager, D, Robinson, RA, Weiner, D & Schwartz, DA (1994). C-erbB-2 expression and codon 12 K-ras mutations both predict shortened survival for patients with pulmonary adenocarcinomas. J Clin Invest 93: 516–520.

    Article  CAS  Google Scholar 

  • Kwa, HB, Michalides, RJ, Dijkman, JH & Mooi, WJ (1996). The prognostic value of NCAM, p53 and cyclin D1 in resected non-small cell lung cancer. Lung Cancer 14: 207–217.

    Article  CAS  Google Scholar 

  • Lovec, H, Sewing, A, Lucibello, FC, Muller, R & Moroy, T (1994). Oncogenic activity of cyclin D1 revealed through cooperation with Ha-ras: link between cell cycle control and malignant transformation. Oncogene 9: 323–326.

    CAS  PubMed  Google Scholar 

  • Lukas, J, Pagano, M, Staskova, Z, Draetta, G & Bartek, J (1994). Cyclin D1 protein oscillates and is essential for cell cycle progression in human tumor cell lines. Oncogene 9: 707–718.

    CAS  PubMed  Google Scholar 

  • Mate, JL, Ariza, A, Aracil, C, Lopez, D, Isamat, M, Perez-Piteira, J & Navas-Palacios, JJ (1996). Cyclin D1 overexpression in non-small cell lung carcinoma: correlation with Ki67 labelling index and poor cytoplasmic differentiation. J Pathol 180: 395–399.

    Article  CAS  Google Scholar 

  • McIntosh, GG, Anderson, JJ, Milton, I, Steward, M, Parr, AH, Thomas, MD, Henry, JA, Angus, B, Lennard, TW & Horne, CH (1995). Determination of the prognostic value of cyclin D1 overexpression in breast cancer. Oncogene 11: 885–891.

    CAS  PubMed  Google Scholar 

  • Michalides, R, van Veelen, N, Hart, A, Loftus, B, Wientjens, E & Balm, A (1995). Overexpression of cyclin D1 correlates with recurrence in a group of forty-seven operable squamous cell carcinomas of the head and neck. Cancer Res 55: 975–978.

    CAS  PubMed  Google Scholar 

  • Mitsudomi, T, Steinberg, SM, Oie, HK, Mulshine, JL, Phelps, R, Viallet, J, Pass, H, Minna, JD & Gazdar, AF (1991). ras gene mutations in non-small cell lung cancers are associated with shortened survival irrespective of treatment intent. Cancer Res 51: 4999–5002.

    CAS  PubMed  Google Scholar 

  • Mitsudomi, T, Oyama, T, Kusano, T, Osaki, T, Nakanishi, R & Shirakusa, T (1993). Mutation of the p53 gene as a predictor of poor prognosis in patients with non-small-cell lung cancer. J Natl Cancer Inst 85: 2018–2023.

    Article  CAS  Google Scholar 

  • Motokura, T & Arnold, A (1993). Cyclins and oncogenesis. Biochem Biophys Acta 1155: 63–78.

    CAS  PubMed  Google Scholar 

  • Mountain, CF (1986). A new international staging system for lung cancer. Chest 89: 225S–233S.

    Article  CAS  Google Scholar 

  • Mountain, CF, Lukeman, JM, Hammer, SP, Chamberlain, DW, Coulson, WF, Page, DL, Victor, TA & Weiland, LH (1987). Lung cancer classification: the relationship of disease extent and cell type to survival in a clinical trials population. J Surg Oncol 35: 147–156.

    Article  CAS  Google Scholar 

  • Muller, D, Millon, R, Lidereau, R, Engelmann, A, Bronner, G, Flesch, H, Eber, M, Methlin, G & Abecassis, J (1994). Frequent amplification of 11q13 DNA markers associated with lymph node involvement in head and neck squamous cell carcinomas. Eur J Cancer B Oral Oncol 30B, 2 113–120.

    Article  CAS  Google Scholar 

  • Nishida, N, Fukuda, Y, Komeda, T, Kita, R, Sando, T, Furukawa, M, Amenomori, M, Shibagaki, I, Nakao, K, Ikenaga, M & Ishizaki, K (1994). Amplification and overexpression of the cyclin D1 gene in aggressive human hepatocellular carcinoma. Cancer Res 54: 3107–3110.

    CAS  PubMed  Google Scholar 

  • Naruke, T, Goya, T, Tsuchiya, R & Suemasu, K (1988). Prognosis and survival in resected lung carcinoma based on the new international staging system. J Thorac Cardiovasc Surg 96: 440–447.

    CAS  PubMed  Google Scholar 

  • Pezzella, F, Turley, H, Kuzu, I, Tungekar, MF, Dunnill, MS, Pierce, CB, Harris, A, Gatter, KC & Mason, DY (1993). bcl-2 protein in non-small-cell lung carcinoma. N Engl J Med 329: 690–694.

    Article  CAS  Google Scholar 

  • Proctor, AJ, Coombs, LM, Cairns, JP & Knowles, MA (1991). Amplification at chromosome 11q13 in transitional cell tumours of the bladder. Oncogene 6: 789–795.

    CAS  PubMed  Google Scholar 

  • Rosvold, E (1996). Prognostic factors for patients with non-small cell lung cancer. In: Current Problems in Cancer. Newer Aspects in the Diagnosis, Treatment, and Prevention of Non-small-cell Lung Cancer. Part II, Williams SD, Goulet R and Thomas G (eds), pp. 272–278. Mosby: Missouri

    Google Scholar 

  • Schuuring, E, Verhoeven, E, van Tinteren, H, Peterse, JL, Nunnink, B, Thunnissen, FB, Devilee, P, Cornelisse, CJ, van de Vijver, MJ & Mooi, WJ (1992). Amplification of genes within the chromosome 11q13 region is indicative of poor prognosis in patients with operable breast cancer. Cancer Res 52: 5229–5234.

    CAS  PubMed  Google Scholar 

  • Shay, JW, Wright, WE, Brasiskyte, D & Van der Haegen, BA (1993). E6 of human papillomavirus type 16 can overcome the M1 stage of immortalization in human mammary epithelial cells but not in human fibroblasts. Oncogene 8: 1407–1413.

    CAS  PubMed  Google Scholar 

  • Shin, KY, Kong, G, Kim, WS, Lee, TY, Woo, YN & Lee, JD (1997). Overexpression of cyclin D1 correlates with early recurrence in superficial bladder cancers. Br J Cancer 75: 1788–1792.

    Article  CAS  Google Scholar 

  • Simpson, JF, Quan, DE, O’Malley, F, Odom-Maryon, T & Clarke, PE (1997). Amplification of CCND1 and expression of its protein product, cyclin D1, in ductal carcinoma in situ of the breast. Am J Pathol 151: 161–168.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tateishi, M, Ishida, T, Mitsudomi, T, Kaneko, S & Sugimachi, K (1991). Prognostic value of c-erbB-2 protein expression in human lung adenocarcinoma and squamous cell carcinoma. Eur J Cancer 27: 1372–1375.

    Article  CAS  Google Scholar 

  • Wang, TC, Cardiff, RD, Zukerberg, L, Lees, E, Arnold, A & Schmidt, EV (1994). Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice. Nature 369: 669–671.

    Article  CAS  Google Scholar 

  • Xu, HJ, Quinlan, DC & Davidson, AG (1994). Altered retinoblastoma protein expression and prognosis in early-stage non-small-cell lung carcinoma. J Natl Cancer Inst 86: 695–699.

    Article  CAS  Google Scholar 

  • Zhang, YJ, Jiang, W, Chen, CJ, Lee, CS, Kahn, SM, Santella, RM & Weinstein, IB (1993). Amplification and overexpression of cyclin D1 in human hepatocellular carcinoma. Biochem Biophys Res Commun 196: 1010–1016.

    Article  CAS  Google Scholar 

  • Zukerberg, LR, Yang, WI, Arnold, A & Harris, NL (1995a). Cyclin D1 (PRAD1) expression in non-Hodgkin’s lymphomas. Detection by immunohistochemistry. Am J Clin Pathol 103: 756–760.

    Article  CAS  Google Scholar 

  • Zukerberg, LR, Yang, WI, Gadd, M, Thor, AD, Koerner, FC, Schmidt, EV & Arnold, A (1995b). Cyclin D1 (PRAD1) protein expression in breast cancer: approximately one-third of infiltrating mammary carcinomas show overexpression of the cyclin D1 oncogene. Mod Pathol 8: 560–567.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, School of Medicine, Sungkyunkwan University, # 108, Pyung-Dong, Chongro-Ku, Seoul, 110-102, Korea

    J S Keum

  2. Department of Pathology, Hanyang University, # 17, Haengdang-Dong, Sungdong-Ku, Seoul, 133-791, Korea

    G Kong & J D Lee

  3. Department of Internal Medicine, College of Medicine, Hanyang University, # 17, Haengdang-Dong, Sungdong-Ku, Seoul, 133-791, Korea

    S C Yang, D H Shin, S S Park & J H Lee

Authors
  1. J S Keum
    View author publications

    Search author on:PubMed Google Scholar

  2. G Kong
    View author publications

    Search author on:PubMed Google Scholar

  3. S C Yang
    View author publications

    Search author on:PubMed Google Scholar

  4. D H Shin
    View author publications

    Search author on:PubMed Google Scholar

  5. S S Park
    View author publications

    Search author on:PubMed Google Scholar

  6. J H Lee
    View author publications

    Search author on:PubMed Google Scholar

  7. J D Lee
    View author publications

    Search author on:PubMed Google Scholar

Rights and permissions

From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

Reprints and permissions

About this article

Cite this article

Keum, J., Kong, G., Yang, S. et al. Cyclin D1 overexpression is an indicator of poor prognosis in resectable non-small cell lung cancer. Br J Cancer 81, 127–132 (1999). https://doi.org/10.1038/sj.bjc.6690661

Download citation

  • Received: 14 August 1998

  • Revised: 27 January 1999

  • Accepted: 11 March 1999

  • Published: 13 August 1999

  • Issue date: 01 September 1999

  • DOI: https://doi.org/10.1038/sj.bjc.6690661

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Keywords

  • non-small-cell lung cancer
  • cyclin D1
  • immunohistochemistry
  • progression
  • prognosis

This article is cited by

  • Immunohistochemical expression of Cyclin D1 among Sudanese patients diagnosed with benign and malignant prostatic lesions

    • Eiman Siddig Ahmed
    • Lubna S. Elnour
    • Ali M. M. Edris

    BMC Research Notes (2020)

  • MicroRNA-92 promotes invasion and chemoresistance by targeting GSK3β and activating Wnt signaling in bladder cancer cells

    • Haifeng Wang
    • Changxing Ke
    • Jiansong Wang

    Tumor Biology (2016)

  • A carbazole alkaloid deactivates mTOR through the suppression of rictor and that induces apoptosis in lung cancer cells

    • Priyajit Chatterjee
    • Soma Seal
    • Samir Bhattacharya

    Molecular and Cellular Biochemistry (2015)

  • Identification of HLA ligands and T-cell epitopes for immunotherapy of lung cancer

    • Anneke Neumann
    • Helen Hörzer
    • Stefan Stevanović

    Cancer Immunology, Immunotherapy (2013)

  • CIP2A is overexpressed in human ovarian cancer and regulates cell proliferation and apoptosis

    • Yuanyuan Fang
    • Zhengtao Li
    • Shulan Zhang

    Tumor Biology (2012)

Download PDF

Advertisement

Explore content

  • Research articles
  • Reviews & Analysis
  • News & Comment
  • Current issue
  • Collections
  • Follow us on X
  • Sign up for alerts
  • RSS feed

About the journal

  • Journal Information
  • Open access publishing
  • About the Editors
  • Contact
  • Special Issues
  • For Advertisers
  • Subscribe

Publish with us

  • For Authors & Referees
  • Language editing services
  • Open access funding
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

British Journal of Cancer (Br J Cancer)

ISSN 1532-1827 (online)

ISSN 0007-0920 (print)

nature.com sitemap

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Awards
  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2026 Springer Nature Limited