Journal List > Tuberc Respir Dis > v.64(5) > 1001229

TOOLS
Hwang, Jo, Lee, Shim, Song, Shin, Shin, Park, Hong, Park, Jeong, Kim, Kim, Yang, and Jeong: The Clinical and Histopathologic Features according to Loss of LKB1 Protein Expression on Primary Lung Cancer
Original Article
Tuberculosis and Respiratory Diseases

Tuberculosis and Respiratory Diseases 2008; 64(5): 362-368.

Published online: 31 May 2008

DOI: https://doi.org/10.4046/trd.2008.64.5.362

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

Ki Eun Hwang, M.D.1, Hyang-Jeong Jo, M.D.2, Kang Kyoo Lee, M.D., Ph.D.3, Hyeok Shim, M.D.1, Jung Sub Song, M.D.1, Jeong Hyun Shin, M.D.1, Seong Nam Shin, M.D.1, Seong-Hoon Park, M.D.4, Kyeong-Man Hong, M.D., Ph.D.5, Jung-Hyun Park, M.D.1, Jong-Hoon Jeong, M.D.1, Hui Jung Kim, M.D.1, Hak-Ryul Kim, M.D., Ph.D.1, Sei-Hoon Yang, M.D., Ph.D.1, Eun-Taik Jeong, M.D., Ph.D.1

1Department of Internal Medicine, College of Medicine, Wonkwang University, Iksan, Korea.

2Department of Pathology, College of Medicine, Wonkwang University, Iksan, Korea.

3Department of Therapeutic Radiology and Oncology, College of Medicine, Wonkwang University, Iksan, Korea.

4Department of Radiology, College of Medicine, Wonkwang University, Iksan, Korea.

5Research Institute, National Cancer Center, Goyang, Korea.

Address for correspondence: Sei-Hoon Yang, M.D., Ph.D. Department of Internal Medicine, Wonkwang University Hospital, 344-2 Shinyong-dong, Iksan 570-711, Korea. Phone: 82-63-859-2582, Fax: 82-63-855-2025, yshpul@wonkwang.ac.kr

Received 24 December 2007       Accepted 13 May 2008

Copyright © 2008 The Korean Academy of Tuberculosis and Respiratory Diseases

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

Figures and Tables

Figure 1
LKB1 protein expression. Positive reaction (arrow head) to LKB1 antigen stain in normal epithelium (A, Hematoxylin counterstain, ×400). Strong positivity (arrow head) to LKB1 antigen in bronchioloalveolar cell carcinoma (BAC) (B, Hematoxylin counterstain, ×400). NE: normal epithelium.
trd-64-362-g001
Figure 2
Kaplan-Meier survival curves for overall survival.
trd-64-362-g002
Table 1
Clinical characteristics of patients
trd-64-362-i001
Table 2
Expression of LKB1 on primary lung cancer
trd-64-362-i002

( ): No. of cases.

Table 3
Expression of LKB1 according to histological cell types
trd-64-362-i003

Adeno: adenocarcinoma; BAC: bronchioloalveolar carcinoma.

*Significant the high rate of negative expression compared to other cell types (p<0.05).

Table 4
Expression of LKB1 according to sex
trd-64-362-i004

*Significant the high rate of negative expression compared to female (p<0.01).

Table 5
Expression of LKB1 according to smoking history
trd-64-362-i005

*Significant the high rate of negative expression compared to Non-smoker (p<0.01). †Non significant the rate of negative expression compared to more than 40 PY (p=0.391).

Table 6
Expression of LKB1 according to tumor site
trd-64-362-i006

*Non significant the rate of negative expression compared to peripheral site (p=0.098).

Table 7
Expression of LKB1 according to smoking history in periphery
trd-64-362-i007

*Significant the rate of negative expression compared to non-smoker in periphery (p=0.02).

Table 8
Expression of LKB1 according to TNM stage
trd-64-362-i008

*Non significant the rate of negative expression compared to each other on three groups (p=0.602).

Table 9
Expression of LKB1 according to T stage
trd-64-362-i009

*Non significant the rate of negative expression compared to more than T2 stage (p=0.086).

Table 10
Expression of LKB1 according to N stage
trd-64-362-i010

*Non significant the rate of negative expression compared to each other on four groups (p=0.237).

References

1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005. 55:74–108.
2. Minna JD, Ginsberg RJ, Ihde DC. DeVita VT, Hellman S, Rosenberg SA, editors. Chapter 30. Cancer of lung. Cancer: principles and practice of oncology. 1997. 5th ed. Philadelphia: Lippincott-Raven Pub.;849.
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. Nature. 1998. 391:184–187.
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. 128:896–899.
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. Cox G, Jones JL, Andi A, Waller DA, O'Byrne KJ. A biological staging model for operable non-small cell lung cancer. Thorax. 2001. 56:561–566.
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. 75:684–689.
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. 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. Tiainen M, Ylikorkala A, Makela TP. Growth suppression by Lkb1 is mediated by a G1 cell cycle arrest. Proc Natl Acad Sci USA. 1999. 96:9248–9251.
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. 8:2085–2090.
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 Cell. 2001. 7:1307–1319.
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. 154:677–681.
14. Ji H, Ramsey MR, Hayes DN, Fan C, McNamara K, Kozlowski P, et al. LKB1 modulates lung cancer differentiation and metastasis. Nature. 2007. 448:807–810.
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. 62:3659–3662.
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. 98:1747–1751.
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. Fraumeni JF JR, Schottenfeld D, Searle JG. Cancer epidemiology and prevention. 1996. 2nd ed. New York: Oxford University Press.
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. 61:1309–1313.
TOOLS
Similar articles