Lab Med Online.  2014 Oct;4(4):218-221. 10.3343/lmo.2014.4.4.218.

A Case of Small Cell Lung Carcinoma with Coexisting Autoantibodies against Proliferating Cell Nuclear Antigen and Centriole Detected Using the Autoimmune Target Test

• Lee ZY
• Kim TY

• KMID: 2312259
• DOI: http://doi.org/10.3343/lmo.2014.4.4.218

Abstract

Approximately 60-70% of small cell lung carcinoma (SCLC) cases are diagnosed at extensive stage, thus tumor markers for its early detection are needed. Autoantibodies associated with malignancy are present before radiographic detection. Autoantibodies detected using the autoimmune target (AIT) test in patients with some tumors have shown the possibility of autoantibodies to be used as a tumor marker. To overcome the limitations of antinuclear antibody (ANA) test using HEp-2 cell line, the AIT test was developed using human macrophage cell line, IT-1, as a substrate, which showed positive identification of various autoantibodies with a higher level of sensitivity. We report a case of SCLC with autoantibodies against proliferating cell nuclear antigen (PCNA) and centriole in a 70-yr-old man who had a history of heavy alcohol consumption and a 50 pack-yr history of smoking. Results of computed tomography of the chest and abdomen showed a lung mass and multiple metastases. Extensive stage SCLC was confirmed using sputum cytology and lymph node aspiration biopsy. Anti-PCNA (1:1,280) and anti-centriolar (1:320) patterns were detected using the AIT test. Neuron-specific enolase was elevated (38.2 ng/mL). There was no evidence of systemic autoimmune rheumatic disease or chronic hepatitis. This is the first case report in which coexisting autoantibodies against PCNA and centriole associated with SCLC were detected using the AIT test. This case provides some evidence that autoantibodies may be used as a tumor marker for SCLC.

Keyword

Autoimmune target test; Autoantibodies; Centriole; Proliferating cell nuclear antigen; Small cell lung carcinoma

MeSH Terms

Abdomen
Alcohol Drinking
Antibodies, Antinuclear
Autoantibodies*
Biopsy, Needle
Cell Line
Centrioles*
Hepatitis, Chronic
Humans
Lung
Lymph Nodes
Macrophages
Neoplasm Metastasis
Phosphopyruvate Hydratase
Proliferating Cell Nuclear Antigen*
Rheumatic Diseases
Small Cell Lung Carcinoma*
Smoke
Smoking
Sputum
Thorax
Biomarkers, Tumor
Antibodies, Antinuclear
Autoantibodies
Phosphopyruvate Hydratase
Proliferating Cell Nuclear Antigen
Smoke

Reference

1. The Korea Central Cancer Registry, National Cancer Center. Annual report of cancer statistics in Korea in 2010. Seoul: Ministry of Health and Welfare;2012. p. 19.

2. Joshi M, Ayoola A, Belani CP. Small-cell lung cancer: an update on targeted therapies. Adv Exp Med Biol. 2013; 779:385–404.

3. Horn L, Pao W, et al. Neoplasms of the lung. In : Longo DL, Kasper DL, editors. Harrison's principles of internal medicine. 18th ed. New York: McGraw Hill;2012. p. 737–753.

4. Zhong L, Coe SP, Stromberg AJ, Khattar NH, Jett JR, Hirschowitz EA. Profiling tumor-associated antibodies for early detection of non-small cell lung cancer. J Thorac Oncol. 2006; 1:513–519.

5. Fernandez-Madrid F, VandeVord PJ, Yang X, Karvonen RL, Simpson PM, Kraut MJ, et al. Antinuclear antibodies as potential markers of lung cancer. Clin Cancer Res. 1999; 5:1393–1400.

6. Yao Y, Fan Y, Wu J, Wan H, Wang J, Lam S, et al. Potential application of non-small cell lung cancer-associated autoantibodies to early cancer diagnosis. Biochem Biophys Res Commun. 2012; 423:613–619.

7. Blaes F, Klotz M, Huwer H, Straub U, Kalweit G, Schimrigk K, et al. Antineural and antinuclear autoantibodies are of prognostic relevance in non-small cell lung cancer. Ann Thorac Surg. 2000; 69:254–258.

8. Woodard KM, Chapman CJ. Lung cancer - can autoantibodies provide an aid to diagnosis? Expert Opin Med Diagn. 2008; 2:911–923.

9. Sir JU, Kim TY. Anti-MTOC-MT antibody is commonly detected by AIT test in colorectal cancer patients. Virchows Arch. 2009; 455:99–100.

10. Mahler M, Miyachi K, Peebles C, Fritzler MJ. The clinical significance of autoantibodies to the proliferating cell nuclear antigen (PCNA). Autoimmun Rev. 2012; 11:771–775.

11. Maga G, Hubscher U. Proliferating cell nuclear antigen (PCNA): a dancer with many partners. J Cell Sci. 2003; 116:3051–3060.

12. Beyne-Rauzy O, Thebault S, Adoue D, Fortenfant F. Anti-PCNA antibodies: prevalence and predictive value. Joint Bone Spine. 2005; 72:432–435.

13. Rattner JB, Martin L, Waisman DM, Johnstone SA, Fritzler MJ. Autoantibodies to the centrosome (centriole) react with determinants present in the glycolytic enzyme enolase. J Immunol. 1991; 146:2341–2344.

14. Hayakawa I, Sato S, Hasegawa M, Echigo T, Takehara K. A case of scleroderma spectrum disorder with anticentriole antibody and pulmonary hypertension. Clin Rheumatol. 2004; 23:266–268.

15. Vermeersch P, De Beeck KO, Lauwerys BR, Van den Bergh K, Develter M, Marien G, et al. Antinuclear antibodies directed against proliferating cell nuclear antigen are not specifically associated with systemic lupus erythematosus. Ann Rheum Dis. 2009; 68:1791–1793.

16. Briasoulis E, Kamposioras K, Tzovaras V, Pafitanis G, Kostoula A, Mavridis A, et al. CENP-B specific anti-centromere autoantibodies heralding small-cell lung cancer. A case study and review of the literature. Lung Cancer. 2008; 60:302–306.

17. Zuber M. Positive antinuclear antibodies in malignancies. Ann Rheum Dis. 1992; 51:573–574.

18. Jearn LH, Kim DA, Kim TY. Limitations of antinuclear antibody tests (HEp-2) are overcome with the autoimmune target test (IT-1) in systemic lupus erythematosus. J Rheumatol. 2009; 36:1833–1834.

19. Mihn DC, Kim TY. Various autoantibodies are found in small-cell lung cancer. Lung Cancer. 2009; 64:250.

20. Nagashio R, Sato Y, Jiang SX, Ryuge S, Kodera Y, Maeda T, et al. Detection of tumor-specific autoantibodies in sera of patients with lung cancer. Lung Cancer. 2008; 62:364–373.