Objectives: To assess the diagnostic value of bronchoalveolar lavage fluid (BALF) ferritin as a lung tumor marker by comparing serum and BALF ferritin concentrations in patients with peripheral lung cancer versus control subjects with benign lung disease, and to examine the theory of ferritin compartmentalization around the tumor area by comparing ferritin concentrations in serum and bilateral (affected and unaffected side) BALF in cancer patients. Methods: Four groups of patients were investigated: 10 control nonsmokers, 10 control smokers, 10 smokers with chronic obstructive pulmonary disease (COPD), and 22 patients with primary bronchogenic carcinoma. A bronchoalveolar lavage (BAL) was performed in all subjects (both sides in 13 oncological patients, one side in the others) and samples of BALF and blood were submitted to biochemical analysis. Results: As a lung tumor marker, BALF ferritin showed 54% sensitivity and 93% specificity and serum ferritin 22% sensitivity and 93% specificity. A significant difference was observed between the two sides in the cancer patients (p = 0.033), and between BALF ferritin from the affected side and COPD patients (p = 0.025). Greater differences were obtained when BALF ferritin in the affected side of cancer patients was compared with values in both control nonsmokers (p < 0.0001) and control smokers (p < 0.001). Conclusions: These findings seem to confirm the relative diagnostic value of BALF ferritin as a lung tumor marker and the theory of ferritin compartmentalization. However, further studies are required to clarify the relations between iron and ferritin on the one hand and inflammation, tumorigenesis and host response on the other.

Keywords:
Ferritin, Bronchoalveolar lavage, Lung cancer, Tumor marker
1.
Niklinski J, Furman M: Clinical tumour markers in lung cancer (109 refs). Eur J Cancer Prevent 1995;4:129–138.
2.
Worwood M: Ferritin in human tissues and serum. Clin Haematol 1982;11:275–307.
3.
Giler S, Moroz C: The significance of ferritin in malignant diseases. Biomedicine 1978;28:203–206.
4.
Konijn AM, Hershko C: The anaemia of inflammation and chronic disease; in De Souza M, Brock JH (eds): Iron in Immunity, Cancer and Inflammation. Chichester, Wiley, 1989, p 111.
5.
Lombardi C, Tassi GF, Pizzocollo G, Donato F: Clinical significance of a multiple biomarker assay in patients with lung cancer. Chest 1990;97:639–644.
6.
Gail MH, Muenz L, McIntire KR, Radovich B, Braunstein G, Brown PR, Deftos L, Dnistrian A, Dunsmore M, Elashoff R, Geller N, W Go VL, Hirji K, Klauber MR, Pee D, Petroni G, Schwartz M, Wolfsen AR: Multiple markers for lung cancer diagnosis: Validation of models for localized lung cancer. J Natl Cancer Inst 1988;80:97–101.
7.
Ferrigno D, Buccheri GF: Serum ferritin levels in lung cancer patients (letter). Eur J Cancer 1992;28:241.
8.
Buccheri GF, Violante B, Sartoris AM, Ferrigno D, Curcio A, Vola F: Clinical value of multiple biomarker assay in patients with bronchogenic carcinoma. Cancer 1986;57:2389–2398.
9.
Bianco A, Marcatili P, D’Auria D, Sorrentino P, Zofra S: Blood tumor markers in patients with lung cancer. Ann Ital Med Interna 1996;11:114–118.
10.
Alvarez Sala R, Blasco R, Callol L, Laguna R, Alvarez Sala JL, Gomez De Terreros FJ: Tumor markers in bronchoalveolar lavage. Acta Oncol (Stockh) 1989;28:290–291.
11.
Macchia V, Mariano A, Cavalcanti M, Coppa A, Cecere C, Fraiolo G, Elia S, Ferrante G: Tumor markers and lung cancer: Correlation between serum and bronchial secretion levels of CEA, TPA, CanAg CA-50, NSE and ferritin. Int J Biol Markers 1987;2:151–156.
12.
Schultek T, Braun J, Wiessmann KJ, Wood WG: Bronchoalveolar lavage: The umoral parameter spectrum in bronchial carcinoma and chronic bronchitis. Dtsch Med Wochenschr 1986;111:333–337.
13.
Son CH, Lee MK, Hong TJ, Chung WT, Park SK, Shin YK: Measurements of carcinoembryonic antigen and ferritin levels in the serum and bronchoalveolar lavage fluid in patients with pulmonary disease. Tuberc Respir Dis 1988;35:92–102.
14.
Maxim PE, Veltri RW, Sprinkle PM: Soluble tumor-associated markers in lung cancer extracts. Oncololgy 1981;38:147–153.
15.
Mountain CF: Revision in the International System for Staging Lung Cancer. Chest 1997;111:1710–1717.
16.
Klech H, Pohl W: Technical recommendations and guidelines for bronchoalveolar lavage (BAL). Eur Resp J 1989;2:561–585.
17.
Auble D: Extended tables for the Mann-Whitney statistic. Bull Inst Educ Res Indiana University, 1953, vol 1.
18.
Goldstein N, Lippmann ML, Goldberg SK, Fein AM, Shapiro B, Leon SA: Usefulness of markers in serum and bronchoalveolar lavage of patients undergoing fiberoptic bronchoscopy. Am Rev Respir Dis 1985;132:60–64.
19.
Nelson ME, O’Brien-Ladner AR, Wesselius LJ: Regional variation in iron and iron-binding proteins within the lungs of smokers. Am J Resp Crit Care Med 1996;153:1353–1358.
20.
Stevens R, Richard G, Kalkwarf DR: Iron, radiation and cancer. Envir Hlth Perspect 1990;87:291–300.
21.
Gayton KZ, Kensler TW: Oxidative mechanisms in carcinogenesis. Br Med Bull 1993;49:523–544.
22.
Cerutti PA: Prooxidant states and tumor promotion. Science 1985;229:375–381.
23.
Feig DI, Reid TM, Loeb LA: Reactive oxygen species in tumorigenesis. Cancer Res 1994;54(suppl):1890–1894.
24.
Cazzola M, Bergamaschi G, Dezza L, Arosio P: Manipulations of cellular iron metabolism for modulating normal and malignant cell proliferation: Achievements and prospects. Blood 1990;75:1903–1919.
25.
Reizenstein P: Iron, free radicals and cancer. Med Oncol Tumor Pharmacother 1991;8:229–233.
26.
Weinberg ED: Cellular iron metabolism in health and disease. Drug Metab Rev 1990;22:531–579.
27.
Halliwell B, Gutteridge JMC: Free Radicals in Biology and Medicine, ed 2. Oxford, Oxford University Press, 1989.
28.
Ames BN, Shigenaga MK, Hagen TM: Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA 1993;90:7915–7922.
29.
Gutteridge JMC, Halliwell B: Iron toxicity and oxygen radicals. Clin Haematol 1989;2:195–256.
30.
Ryrfeldt A, Bannenber G, Moldus O: Free radicals and lung disease. Br Med Bull 1993;49:588–603.
31.
Thompson AB, Bohling T, Heires A, Linder J, Rennard SI: Lower respiratory tract iron burden is increased in association with cigarette smoking. J Lab Clin Med 1991;117:493–499.
32.
Thompson AB, Bohling T, Payvandi F, Rennard SI: Lower respiratory tract lactoferrin and lysozyme arise primarily in the airways and are elevated in association with chronic bronchitis. J Lab Clin Med 1990;115:148–158.
33.
Corhay JL, Weber G, Bury Th, Mariz S, Roelandts I, Radermecker MF: Iron content in human alveolar macrophages. Eur Respir J 1992;5:804–809.
34.
Dietemann-Molard A, Maier E, Pelletier A, Hutt N, Maier A, Bohner C, Pauli G, Leroy MJF, Roegel E: Etude multiélémentaire des composants inorganiques due liquide de lavage bronchoalvéolaire chez le sujet normal et dans diverses pathologies pulmonaires. Rev Mal Respir 1989;6:511–517.
35.
McGowan SE, Henley SA: Iron and ferritin contents and distribution in human alveolar macrophages. J Lab Clin Med 1988;111:611–617.
36.
Wesselius LJ, Flowers CH, Skikne BS: Alveolar macrophage content of isoferritins and transferrin: A comparison of non-smokers and smokers with and without chronic airflow obstruction. Am Rev Respir Dis 1992;145:311–316.
37.
Mims CA: The Pathogenesis of Infectious Diseases. London/New York, Academic Press/Grune & Stratton, 1976, p 213.
38.
Braude AI: Mechanisms of natural resistance to infections; in Braude AI, Davis CE, Fierer J (eds): Medical Microbiology and Infectious Disease, Philadelphia, Saunders, 1981, pp 739–764.
39.
Beisel WR: Metabolic effect of infection; in Braude AI, Davis CE, Fierer J (eds): Medical Microlbiology and Infectious Disease. Philadelphia, Saunders, 1981, pp 803–808.
1999
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.