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The Clinical and Histopathologic Features according to Loss of LKB1 Protein Expression on Primary Lung Cancer

Tuberculosis & Respiratory Diseases / Tuberculosis & Respiratory Diseases,
2008, v.64 no.5, pp.362-368















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Abstract

Background: LKB1(STK11) is a serine/threonine kinase that functions as a tumor growth suppressor. The functions of LKB1 in lung cancer are not completely understood. This study evaluated the relationship between LKB1 protein expression and the clinicopathological features in lung cancer tissues. Methods: The expression of LKB1 was studied in paraffin-embedded tumor blocks, which were obtained from 77 patients who had undergone surgery at Wonkwang University Hospital. The expression of the LKB1 protein was considered positive if the staining intensity in the tumor tissue adjacent to the normal airway epithelium was >30%. Results: The LKB1 expression was positive in 31 (40%) of samples. Loss of LKB1 expression was significantly associated with being male, smoking history, and squamous cell carcinoma. In the peripheral sites, the loss of LKB1 expression was strongly associated with a smoking history. A loss of LKB1 expression was more frequently associated with progression according to TNM staging, particularly more than T2, N progression. Conclusion: There was a significant relationship between the loss of the LKB1 protein and gender, smoking history, and histological type in primary lung cancer. Although LKB1 expression was not found to be a significant prognostic factor, further studies with a larger cohort of patient's lung cancer tissue samples will be needed to confirm this.

keywords
LKB1, Gender, Smoking, Lung cancer

Reference

1.

1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74-108.

2.

2. Minna JD, Ginsberg RJ, Ihde DC. Chapter 30. Cancer of lung. In: DeVita VT, Hellman S, Rosenberg SA,editors. Cancer: principles and practice of oncology.5th ed. Philadelphia: Lippincott-Raven Pub.; 1997. p.849.

3.

3. Hemminki A, Markie D, Tomlinson I, Avizienyte E,Roth S, Loukola A, et al. A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature1998;391:184-7.

4.

4. Boardman LA, Thibodeau SN, Schaid DJ, Lindor NM,McDonnell SK, Burgart LJ, et al. Increased risk for cancer in patients with the Peutz-Jeghers syndrome. Ann Intern Med 1998;128:896-9.

5.

5. Ghaffar H, Sahin F, Sanchez-Cepedes M, Su GH,Zahurak M, Sidransky D, et al. LKB1 protein expression in the evolution of glandular neoplasia of the lung. Clin Cancer Res 2003;9:2998-3003.

6.

6. Cox G, Jones JL, Andi A, Waller DA, O'Byrne KJ. A biological staging model for operable non-small cell lung cancer. Thorax 2001;56:561-6.

7.

7. Diez M, Pollán M, Maestro M, Torres A, Ortega D,Gómez A, et al. Prediction of recurrence by quantification of p185neu protein in non-small cell lung cancer tissue. Br J Cancer 1997;75:684-9.

8.

8. Hemminki A, Tomlinson I, Markie D, Järvinen H,Sistonen P, Björkqvist AM, et al. Localization of a susceptibility locus for Peutz-Jeghers syndrome to 19p using comparative genomic hybridization and targeted linkage analysis. Nat Genet 1997;15:87-90.

9.

9. Jenne DE, Reimann H, Nezu J, Friedel W, Loff S,Jeschke R, et al. Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat Genet 1998;18:38-43.

10.

10. Tiainen M, Ylikorkala A, Makela TP. Growth suppression by Lkb1 is mediated by a G1 cell cycle arrest.Proc Natl Acad Sci USA 1999;96:9248-51.

11.

11. Shen Z, Wen XF, Lan F, Shen ZZ, Shao ZM. The tumor suppressor gene LKB1 is associated with prognosis in human breast carcinoma. Clin Cancer Res 2002;8:2085-90.

12.

12. Karuman P, Gozani O, Odze RD, Zhou XC, Zhu H,Shaw R, et al. The Peutz–Jegher gene product LKB1 is a mediator of p53-dependent cell death. Mol Cell2001;7:1307-19.

13.

13. Avizienyte E, Loukola A, Roth S, Hemminki A,Tarkkanen M, Salovaara R, et al. LKB1 somatic mutations in sporadic tumors. Am J Pathol 1999;154:677-81.

14.

14. Ji H, Ramsey MR, Hayes DN, Fan C, McNamara K,Kozlowski P, et al. LKB1 modulates lung cancer differentiation and metastasis. Nature 2007;448:807-10.

15.

15. Sanchez-Cespedes M, Parrella P, Esteller M, Nomoto S,Trink B, Engles JM, et al. Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung.Cancer Res 2002;62:3659-62.

16.

16. Onozato R, Kosaka T, Achiwa H, Kuwano H, Takahashi T, Yatabe Y, et al. LKB1 gene mutations in Japanese lung cancer patients. Cancer Sci 2007;98:1747-51.

17.

17. Parkin DM, Pisani P, Lopez AD, Masuyer E. At least one in seven cases of cancer is caused by smoking.Int J Cancer 1994;59:494-504.

18.

18. Fraumeni JF JR, Schottenfeld D, Searle JG. Cancer epidemiology and prevention. 2nd ed. New York: Oxford University Press; 1996.

19.

19. Sanchez-Cespedes M, Ahrendt SA, Piantadosi S, Rosell R, Monzo M, Wu L, et al. Chromosomal alterations in lung adenocarcinoma from smokers and nonsmokers.Cancer Res 2001;61:1309-13.

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