| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Molecular Oncology, Markers, Clinical Correlates |
Departments of Pathology [H. G., F. S., G. H. S., W. H. W.], Oncology [G. H. S.], OncologyBiostatistics [M. Z.], and Otolaryngology-Head and Neck Surgery [D. S., W. H. W.], The Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, and the Molecular Pathology Program, Spanish National Cancer Center, Madrid, Spain [M. S-C.]
Purpose: About one-third of sporadic lung adenocarcinomas demonstrates biallelic inactivation of the LKB1 gene, but the timing of this event is not known.
Design: We performed LKB1 immunohistochemistry on 35 primary lung adenocarcinomas and 96 atypical adenomatous hyperplasias (AAH), a form of early glandular neoplasia from which some lung adenocarcinomas arise.
Results: In all cases, strong cytoplasmic staining was noted in the non-neoplastic epithelium lining the airways from the bronchi to the terminal bronchioles. There was a marked reduction in LKB1 staining in 9 of 35 (26%) adenocarcinomas and in 10 of 96 (10%) AAHs. When the AAHs were subclassified on the basis of cytoarchitectural atypia, loss of LKB1 expression was more frequent in the high-grade lesions (7 of 33, 21%) than low-grade lesions (3 of 63, 5%; P = 0.021). For the 21 adenocarcinomas where the genetic status was known, immunohistochemistry staining reliably reflected the activational state of the LKB1 gene (95% concordancy).
Conclusions: In AAH, loss of LKB1 expression is strongly associated with severe dysplasia, suggesting that LKB1 inactivation may play a role in the critical transition from premalignant to malignant tumor growth.
This article has been cited by other articles:
|
|
 |
|
  R. S. Herbst, J. V. Heymach, and S. M. Lippman Lung Cancer N. Engl. J. Med., September 25, 2008; 359(13): 1367 - 1380. [Full Text] [PDF]
|
|
|
|
 |
|
 J. D.F. Licchesi, W. H. Westra, C. M. Hooker, E. O. Machida, S. B. Baylin, and J. G. Herman Epigenetic alteration of Wnt pathway antagonists in progressive glandular neoplasia of the lung Carcinogenesis, May 1, 2008; 29(5): 895 - 904. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Contreras, S. Gurumurthy, J. M. Haynie, L. J. Shirley, E. A. Akbay, S. N. Wingo, J. O. Schorge, R. R. Broaddus, K.-K. Wong, N. Bardeesy, et al. Loss of Lkb1 Provokes Highly Invasive Endometrial Adenocarcinomas Cancer Res., February 1, 2008; 68(3): 759 - 766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Memmott, J. J. Gills, M. Hollingshead, M. C. Powers, Z. Chen, B. Kemp, A. Kozikowski, and P. A. Dennis Phosphatidylinositol Ether Lipid Analogues Induce AMP-Activated Protein Kinase Dependent Death in LKB1-Mutant Non Small Cell Lung Cancer Cells Cancer Res., January 15, 2008; 68(2): 580 - 588. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Wagner, J. E. Mullally, and F. A. Fitzpatrick Reactive Lipid Species from Cyclooxygenase-2 Inactivate Tumor Suppressor LKB1/STK11: CYCLOPENTENONE PROSTAGLANDINS AND 4-HYDROXY-2-NONENAL COVALENTLY MODIFY AND INHIBIT THE AMP-KINASE KINASE THAT MODULATES CELLULAR ENERGY HOMEOSTASIS AND PROTEIN TRANSLATION J. Biol. Chem., February 3, 2006; 281(5): 2598 - 2604. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P A Marignani LKB1, the multitasking tumour suppressor kinase J. Clin. Pathol., January 1, 2005; 58(1): 15 - 19. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
