Overexpression of cyclin B1 in early-stage non-small cell lung cancer and its clinical implication.

Cyclin B1 is a key molecule for G2-M-phase transition during the cell cycle and is overexpressed in various tumor types. However, the expression status of cyclin B1 in lung cancer and its clinical significance remain unknown. We used immunohistochemistry studies to examine the expression of cyclin B1 in 77 non-small cell lung cancer specimens from patients with histological stage I disease. All of the patients underwent curative surgical treatment. The median length of follow-up care is 8.2 years. High-level cyclin B1 expression (a cyclin B1 labeling index > or =15%) was observed in 17 of the 77 (22%) tumors. Patients whose tumors expressed a high level of cyclin B1 had a significantly shorter survival time than patients whose tumors expressed a low level of cyclin B1 (P = 0.02, log-rank test). Interestingly, overexpression of cyclin B1 was more frequently observed in tumors with squamous cell histology than in tumors with other histological cell types (P = 0.01, Fisher's exact test). A subgroup analysis revealed that cyclin B1 overexpression seems to be an adverse prognostic factor only in patients with squamous cell carcinoma (SCC) of the lung (P = 0.02, log-rank test). Our data indicate that cyclin B1 may be dysregulated in non-small cell lung cancer, particularly in the SCC subtype, and that a high level of cyclin B1 expression may be a prognostic marker for patients with early-stage SCC of the lung.

[1]  K. Ohshima,et al.  Expressions of cyclin E, A, and B1 in Hodgkin and Reed–Sternberg cells: Not suppressed by cyclin‐dependent kinase inhibitor p21 expression , 1999, Pathology international.

[2]  Z. Darżynkiewicz,et al.  Unscheduled expression of cyclin B1 and cyclin E in several leukemic and solid tumor cell lines. , 1994, Cancer research.

[3]  J. Richie,et al.  Expression of cell cycle-regulated proteins in prostate cancer. , 1996, Cancer research.

[4]  M. Furihata,et al.  Determination of the prognostic significance of cyclin B1 overexpression in patients with esophageal squamous cell carcinoma , 1999, Virchows Archiv.

[5]  J. Mate,et al.  Prognostic impact of mutated K-ras gene in surgically resected non-small cell lung cancer patients. , 1993, Oncogene.

[6]  C. Sherr Cancer Cell Cycles , 1996, Science.

[7]  Jennifer Kushner,et al.  Aberrant expression of cyclin A and cyclin B1 proteins in oral carcinoma. , 2007, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[8]  R. Dodge,et al.  Prognostic significance of the proliferation index in surgically resected non-small-cell lung cancer. , 1993, Archives of surgery.

[9]  F. Mertens,et al.  Amplification of cyclin D1 in squamous cell carcinoma of the head and neck and the prognostic value of chromosomal abnormalities and cyclin D1 overexpression , 1997, Cancer.

[10]  H. Koizumi,et al.  Expression of the G2-M checkpoint regulators cyclin B1 and cdc2 in nonmalignant and malignant human breast lesions: immunocytochemical and quantitative image analyses. , 1997, The American journal of pathology.

[11]  G Bussolati,et al.  Value of Ki-67 immunostaining in preoperative biopsies of carcinomas of the lung. , 1997, Human pathology.

[12]  T. Sekiya,et al.  Aberrations of the p53 tumor suppressor gene in human non-small cell carcinomas of the lung. , 1992, Cancer research.

[13]  D. Mason,et al.  Ki‐67 immunostaining and survival in operable lung cancer , 1991, Histopathology.

[14]  Taylor Murray,et al.  Cancer statistics, 2000 , 2000, CA: a cancer journal for clinicians.

[15]  P. Demoly,et al.  Hypodiploidy, Ki-67 growth fraction and prognosis of surgically resected lung cancers. , 1996, British Journal of Cancer.

[16]  W F Taylor,et al.  Survival of patients surgically treated for stage I lung cancer. , 1981, The Journal of thoracic and cardiovascular surgery.

[17]  N. Nishida,et al.  Amplification and overexpression of the cyclin D1 gene in aggressive human hepatocellular carcinoma. , 1994, Cancer research.

[18]  B. Angus,et al.  Determination of the prognostic value of cyclin D1 overexpression in breast cancer. , 1995, Oncogene.

[19]  S. Kim,et al.  Constitutive activation of cyclin B1-associated cdc2 kinase overrides p53-mediated G2-M arrest. , 2000, Cancer research.

[20]  R. Cherian,et al.  Expression of cdc2 and cyclin B1 in Helicobacter pylori-associated gastric MALT and MALT lymphoma : relationship to cell death, proliferation, and transformation. , 2000, The American journal of pathology.

[21]  N. Weidner,et al.  Prognostic significance of Ki-67 immunostaining and symptoms in resected stage I and II non-small cell lung cancer. , 1998, Lung cancer.

[22]  K. Sasaki,et al.  Intracellular localization of cyclin B1 during the cell cycle in glioma cells. , 1996, Cytometry.

[23]  J. M. Lee,et al.  p53 regulates a G2 checkpoint through cyclin B1. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[24]  G. Scagliotti,et al.  Prognostic significance of Ki67 labelling in resected non small cell lung cancer. , 1993, European journal of cancer.