Skip to main content

Expression of FAK and PTEN in Bronchioloalveolar Carcinoma and Lung Adenocarcinoma

Abstract

Bronchioloalveolar carcinoma (BAC) is classified as a subset of lung adenocarcinoma but has a distinct clinical presentation, tumor biology, response to therapy, and prognosis compared with other subtypes of lung adenocarcinoma. This study was designed to investigate the clinicopathological differences between BAC and adenocarcinoma and the expression of focal adhesion kinase (FAK) and phosphatase and tensin homologue (PTEN) and their clinical significance in BAC and adenocarcinoma. A retrospective analysis was performed on 77 patients with BAC and 172 patients with pure adenocarcinoma seen during the period from January 1998 to December 2000. All patients underwent lobectomy or pneumonectomy and systematic lymph node dissection. Paraffin-embedded tissue blocks from these patients were obtained and expressions of PTEN and FAK were evaluated by using immunohistochemical staining. Clinicopathological characteristics and survival outcome were reviewed and compared between patients with BAC and adenocarcinoma. Lymph node status, clinical symptoms, CT appearance and expression of FAK were different between BAC and adenocarcinoma. The overall survival of BAC was better than that of adenocarcinoma. In patients with FAK(−), the overall survival was not different between BAC and adenocarcinoma. In patients with adenocarcinoma, the overall survival was better for FAK(−) compared with FAK(+). Expression of PTEN had a prognostic significance in patients with BAC and adenocarcinoma. BAC and adenocarcinoma have different clinicopathological presentations. Expression of FAK has some effect on such differences and affects survival of lung adenocarcinoma. Expression of PTEN can predict outcome of resected lung adenocarcinoma and BAC.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. Liebow AA (1960) Bronchiolo-alveolar carcinoma. Adv Intern Med 10:329–358

    PubMed  CAS  Google Scholar 

  2. Travis WD, Colby TV, Corrin B et al (1999) Histological typing of lung and pleural tumors, 3rd edn. Springer, Berlin

    Google Scholar 

  3. West HL, Crowley JJ, Vance RB et al (2005) Advanced bronchioloalveolar carcinoma: a phase II trial of paclitaxel by 96-h infusion (SWOG 9714): A Southwest Oncology Group Study. Ann Oncol 16:1076–1080. doi:10.1093/annonc/mdi215

    PubMed  Article  CAS  Google Scholar 

  4. Raz DJ, He B, Rosell R, Jablons DM (2006) Bronchioloalveolar carcinoma: a review. Clin Lung Cancer 7:313–322. doi:10.3816/CLC.2006.n.012

    PubMed  Article  CAS  Google Scholar 

  5. Furak J, Trojan I, Szokr T et al (2003) Bronchioloalveolar lung cancer: occurrence, surgical treatment and survival. Eur J Cardiothorac Surg 23:818–823. doi:10.1016/S1010-7940(03)00084-8

    PubMed  Article  Google Scholar 

  6. Gabarra-Niecko V, Schaller MD, Dunty JM (2003) FAK regulates biological processes important for pathogenesis of cancer. Cancer Metastasis Rev 22:359–374. doi:10.1023/A:1023725029589

    PubMed  Article  CAS  Google Scholar 

  7. Hecker TP, Gladson CL (2003) Focal adhesion kinase in cancer. Front Biosci 8:s705–s714. doi:10.2741/1115

    PubMed  Article  CAS  Google Scholar 

  8. Siesser PMF, Hanks SK (2006) The signaling and biological implications of FAK overexpression in cancer. Clin Cancer Res 12:3233–3237. doi:10.1158/1078-0432.CCR-06-0456

    PubMed  Article  CAS  Google Scholar 

  9. Sansal I, Sellers WR (2004) The biology and clinical relevance of the PTEN tumor suppressor pathway. J Clin Oncol 22:2954–2963. doi:10.1200/JCO.2004.02.141

    PubMed  Article  CAS  Google Scholar 

  10. Tsuruta H, Kishimoto H, Sasaki T, Horie Y, Natsui M et al (2006) Hyperplasia and carcinomas in PTEN-deficient mice and reduced PTEN protein in human bladder cancer patients. Cancer Res 66:8389–8396. doi:10.1158/0008-5472.CAN-05-4627

    PubMed  Article  CAS  Google Scholar 

  11. Haiman CA, Stram DO, Cheng I, Giorgi EE, Pooler L et al (2006) Common genetic variation at PTEN and risk of sporadic breast and prostate cancer. Epidemiol Biomarkers Prev 15:1021–1025

    Article  CAS  Google Scholar 

  12. Mountain CF, Dresler CM (1997) Regional lymph node classification for lung cancer staging. Chest 111:1718–1723. doi:10.1378/chest.111.6.1718

    PubMed  Article  CAS  Google Scholar 

  13. Barsky SH, Cameron R, Osann KE et al (1994) Rising incidence of bronchioloalveolar lung carcinoma and its unique clinicopathological features. Cancer 73:1163–1170. doi:10.1002/1097-0142(19940215)73:4<1163::AID-CNCR2820730407>3.0.CO;2-J

    PubMed  Article  CAS  Google Scholar 

  14. Auerbach O, Garfinkel L (1991) The changing pattern of lung carcinoma. Cancer 68:1973–1977. doi:10.1002/1097-0142(19911101)68:9<1973::AID-CNCR2820680921>3.0.CO;2-Z

    PubMed  Article  CAS  Google Scholar 

  15. Han EK, Mcgonigal T, Wang J, Giranda VL, Luo Y (2004) Functional analysis of focal adhesion kinase (FAK) reduction by small inhibitory RNAs. Anticancer Res 24:3899–3905

    Google Scholar 

  16. Li J, Yen C, Liaw D et al (1997) PTEN, a putativeprotein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275:1943–1947. doi:10.1126/science.275.5308.1943

    PubMed  Article  CAS  Google Scholar 

  17. Tamura M, Gu J, Danen EH et al (1999) PTEN interactions with focal adhesion kinase and suppression of the extracellular matrix-dependent phosphatidylinositol 3-kinase/Akt cell survival pathway. J Biol Chem 274:20693–20703. doi:10.1074/jbc.274.29.20693

    PubMed  Article  CAS  Google Scholar 

  18. Bepler G, Sharma S, Cantor A, Gautam A, Haura E, Simon G, Sharma A, Sommers E, Robinson L (2004) RRM1 and PTEN as prognostic parameters for overall and disease-free survival in patients with non–small-cell lung cancer. J Clin Oncol 22:1878–1885. doi:10.1200/JCO.2004.12.002

    PubMed  Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Zhenfa Zhang.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Wang, C., Yang, R., Yue, D. et al. Expression of FAK and PTEN in Bronchioloalveolar Carcinoma and Lung Adenocarcinoma. Lung 187, 104–109 (2009). https://doi.org/10.1007/s00408-008-9130-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00408-008-9130-6

Keywords

  • Bronchioloalveolar carcinoma
  • Adenocarcinoma
  • Focal adhesion kinase
  • Phosphatase and tensin homologue