Clinical Cancer Research, Vol 1, Issue 6 659-664, Copyright © 1995 by American Association for Cancer Research

ARTICLES

Localized adenocarcinoma of the lung: oncogene expression of erbB-2 and p53 in 150 patients

DH Harpole Jr, JR Marks, WG Richards, JE Herndon 2nd and DJ Sugarbaker
Lung Cancer Research Laboratory, Division of Thoracic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

Historical information and pathological material from 150 consecutive patients with localized adenocarcinoma of the lung was collected to evaluate oncogene expression of erbB-2 and p53, and erbB-2 gene amplification. Pathological material after resection was reviewed to verify histological staging, and patient follow-up was complete in all cases for at least 68 months. Immunohistochemistry of erbB-2 (HER-2/neu) and p53 oncogene expression was performed on two separate paraffin tumor blocks for each patient with normal lung as control. Gene amplification of erbB-2 was measured after DNA extraction from 20-micrometer sections of erbB-2-positive and -negative tumors. All analyses were blinded and included Kaplan-Meier survival estimates with Cox proportional hazards regression modeling. Two adequate blocks of tumor and normal lung were available for 138 (92%) patients. Immunohistochemical identification of expression of p53 was observed in 49 (37%) patients and erbB-2 in 17 (13%) patients. DNA dot blot analyses were performed on 17 erbB-2-positive and 13 randomly selected erbB-2-negative tumors. There was 1 (6%) of 17 erbB-2-positve tumors with 4-fold erbB-2 gene amplification. Actual 5-year survival was 63% and actuarial 10-year survival was 59% for the entire population of 150 patients. Significant univariate predictors (P < 0.05) of cancer death were the presence of symptoms, tumor size >3 cm, poor differentiation, visceral pleural invasion, and p53 expression. Multivariate analysis associated symptoms and p53 expression as independent factors with decreased survival. Thus, this project examined p53 and erbB-2 expression in patients with localized adenocarcinoma and associated p53 status with survival. Multicenter collection of data should allow the development of a model of cancer recurrence in this most common lung cancer.

This article has been cited by other articles:

				U. Gatzemeier, G. Groth, C. Butts, N. Van Zandwijk, F. Shepherd, A. Ardizzoni, C. Barton, P. Ghahramani, and V. Hirsh Randomized phase II trial of gemcitabine-cisplatin with or without trastuzumab in HER2-positive non-small-cell lung cancer Ann. Onc., January 1, 2004; 15(1): 19 - 27. [Abstract] [Full Text] [PDF]

				P. Heinmoller, C. Gross, K. Beyser, C. Schmidtgen, G. Maass, M. Pedrocchi, and J. Ruschoff HER2 Status in Non-Small Cell Lung Cancer: Results from Patient Screening for Enrollment to a Phase II Study of Herceptin Clin. Cancer Res., November 1, 2003; 9(14): 5238 - 5243. [Abstract] [Full Text] [PDF]

				R. J. Korst and R. G. Crystal Active, specific immunotherapy for lung cancer: hurdles and strategies using genetic modification Ann. Thorac. Surg., October 1, 2003; 76(4): 1319 - 1326. [Abstract] [Full Text] [PDF]

				W Hilbe, S Dirnhofer, F Oberwasserlechner, W Eisterer, K Ammann, T Schmid, G Hilbe, J Thaler, and E Woll Immunohistochemical typing of non-small cell lung cancer on cryostat sections: correlation with clinical parameters and prognosis J. Clin. Pathol., October 1, 2003; 56(10): 736 - 741. [Abstract] [Full Text] [PDF]

				T.-L. Hung, F.-F. Chen, J. M. Liu, W.-W. Lai, A.-L. Hsiao, W.-T. Huang, H. H. W. Chen, and W.-C. Su Clinical Evaluation of HER-2/neu Protein in Malignant Pleural Effusion-Associated Lung Adenocarcinoma and as a Tumor Marker in Pleural Effusion Diagnosis Clin. Cancer Res., July 1, 2003; 9(7): 2605 - 2612. [Abstract] [Full Text] [PDF]

				A. A. Adjei, G. K. Dy, C. Erlichman, J. M. Reid, J. A. Sloan, H. C. Pitot, S. R. Alberts, R. M. Goldberg, L. J. Hanson, P. J. Atherton, et al. A Phase I Trial of ISIS 2503, an Antisense Inhibitor of H-ras, in Combination with Gemcitabine in Patients with Advanced Cancer Clin. Cancer Res., January 1, 2003; 9(1): 115 - 123. [Abstract] [Full Text] [PDF]

				Y.-C. Lee, C.-T. Wu, C.-S. Chen, H.-H. Hsu, and Y.-L. Chang The significance of E-cadherin and {alpha}-, {beta}-, and {gamma}-catenin expression in surgically treated non-small cell lung cancers of 3 cm or less in size J. Thorac. Cardiovasc. Surg., March 1, 2002; 123(3): 502 - 507. [Abstract] [Full Text] [PDF]

				C. J. Piyathilake, A. R. Frost, U. Manne, H. Weiss, W. C. Bell, D. C. Heimburger, and W. E. Grizzle Differential Expression of Growth Factors in Squamous Cell Carcinoma and Precancerous Lesions of the Lung Clin. Cancer Res., March 1, 2002; 8(3): 734 - 744. [Abstract] [Full Text] [PDF]

				E. Steels, M. Paesmans, T. Berghmans, F. Branle, F. Lemaitre, C. Mascaux, A.P. Meert, F. Vallot, J.J. Lafitte, and J.P. Sculier Role of p53 as a prognostic factor for survival in lung cancer: a systematic review of the literature with a meta-analysis Eur. Respir. J., October 1, 2001; 18(4): 705 - 719. [Abstract] [Full Text] [PDF]

				P. A. Bunn Jr., B. Helfrich, A. F. Soriano, W. A. Franklin, M. Varella-Garcia, F. R. Hirsch, A. Baron, C. Zeng, and D. C. Chan Expression of Her-2/neu in Human Lung Cancer Cell Lines by Immunohistochemistry and Fluorescence in Situ Hybridization and its Relationship to in Vitro Cytotoxicity by Trastuzumab and Chemotherapeutic Agents Clin. Cancer Res., October 1, 2001; 7(10): 3239 - 3250. [Abstract] [Full Text] [PDF]

				J. Brabender, K. D. Danenberg, R. Metzger, P. M. Schneider, J. Park, D. Salonga, A. H. Holscher, and P. V. Danenberg Epidermal Growth Factor Receptor and HER2-neu mRNA Expression in Non-Small Cell Lung Cancer Is Correlated with Survival Clin. Cancer Res., July 1, 2001; 7(7): 1850 - 1855. [Abstract] [Full Text] [PDF]

				T. Mitsudomi, N. Hamajima, M. Ogawa, and T. Takahashi Prognostic Significance of p53 Alterations in Patients with Non-Small Cell Lung Cancer: A Meta-Analysis Clin. Cancer Res., October 1, 2000; 6(10): 4055 - 4063. [Abstract] [Full Text]

				T. Hashimoto, Y. Tokuchi, M. Hayashi, Y. Kobayashi, K. Nishida, S.-i. Hayashi, Y. Ishikawa, S. Tsuchiya, K. Nakagawa, J.-i. Hayashi, et al. p53 Null Mutations Undetected by Immunohistochemical Staining Predict a Poor Outcome with Early-Stage Non-Small Cell Lung Carcinomas Cancer Res., November 1, 1999; 59(21): 5572 - 5577. [Abstract] [Full Text] [PDF]

				T. A. D'Amico, MD, M. Massey, MD, J. E. Herndon II, PhD, M.-B. Moore, and D. H. Harpole Jr A BIOLOGIC RISK MODEL FOR STAGE I LUNG CANCER: IMMUNOHISTOCHEMICAL ANALYSIS OF 408 PATIENTS WITH THE USE OF TEN MOLECULAR MARKERS J. Thorac. Cardiovasc. Surg., April 1, 1999; 117(4): 736 - 743. [Abstract] [Full Text] [PDF]

				D. H. Harpole Jr Invited commentary Ann. Thorac. Surg., October 1, 1998; 66(4): 1163 - 1164. [Full Text] [PDF]

				D. H. Harpole Jr, W. G. Richards, J. E. Herndon II, and D. J. Sugarbaker Angiogenesis and Molecular Biologic Substaging in Patients With Stage I Non-Small Cell Lung Cancer Ann. Thorac. Surg., May 1, 1996; 61(5): 1470 - 1476. [Abstract] [Full Text]