Skip to main content
PMC home page
Thorax logoLink to Thorax
. 1995 Feb;50(2):116–120. doi: 10.1136/thx.50.2.116

Reliability of commercially available immunocytochemical markers for identification of neuroendocrine differentiation in bronchoscopic biopsies of bronchial carcinoma.

J R Gosney 1, M A Gosney 1, M Lye 1, S A Butt 1
PMCID: PMC473891  PMID: 7701447

Abstract

BACKGROUND--Although neuroendocrine differentiation occurs quite commonly in non-small cell bronchial malignancies, its biological significance and implications for management remain uncertain. Determining these facts requires its recognition early, ideally at diagnosis, which is usually made on tissue from bronchoscopy, but the best means of its detection in such material is unclear. A prospective comparative study was performed of 10 commercially available antisera to a series of markers of neuroendocrine differentiation, to test their efficacy when applied to fibreoptic bronchoscopy biopsy specimens. METHODS--Expression of chromogranin A, synaptophysin, neurone-specific enolase, protein gene product 9.5, the BB isoenzyme of creatine kinase, gastrin releasing peptide, adrenocorticotrophic hormone, calcitonin, calcitonin gene related peptide, and leucine enkephalin was sought by immunolabelling of bronchoscopic biopsy tissue from 83 primary bronchial carcinomas, 22 of them of small cell type. RESULTS--Only synaptophysin and chromogranin were sensitive and specific enough for neuroendocrine differentiation to discriminate between small cell and non-small cell lesions, whereas protein gene product 9.5 and creatine kinase were neither particularly sensitive nor specific and neurone-specific enolase actually labelled more non-small cell tumours than small cell lesions. Of the five secretory products sought, only gastrin releasing peptide was detectable in just one tumour. Three squamous and two morphologically undifferentiated tumours immunolabelled for synaptophysin and chromogranin, almost certainly indicating neuroendocrine differentiation in the absence of small cell morphology. CONCLUSIONS--Of the markers studied, only synaptophysin and chromogranin were sufficiently specific and sensitive for neuroendocrine differentiation to justify their inclusion in any panel of antibodies used in its detection in tissue obtained at fibreoptic brochoscopy.

Full text

PDF
119

Images in this article

118Image
on p.118
119Image
on p.119

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Addis B. J., Hamid Q., Ibrahim N. B., Fahey M., Bloom S. R., Polak J. M. Immunohistochemical markers of small cell carcinoma and related neuroendocrine tumours of the lung. J Pathol. 1987 Oct;153(2):137–150. doi: 10.1002/path.1711530207. [DOI] [PubMed] [Google Scholar]
  2. Ariyoshi Y., Kato K., Ueda R., Takahashi T., Sato T., Akatsuka H., Kuwabara M., Kito K., Suchi T., Nishimura M. Biological and clinical implication of neuron-specific enolase and creatine kinase BB in small cell lung cancer. Jpn J Clin Oncol. 1986 Sep;16(3):213–221. [PubMed] [Google Scholar]
  3. Bepler G., Jaques G., Koehler A., Gropp C., Havemann K. Markers and characteristics of human SCLC cell lines. Neuroendocrine markers, classical tumor markers, and chromosomal characteristics of permanent human small cell lung cancer cell lines. J Cancer Res Clin Oncol. 1987;113(3):253–259. doi: 10.1007/BF00396382. [DOI] [PubMed] [Google Scholar]
  4. Berendsen H. H., de Leij L., Poppema S., Postmus P. E., Boes A., Sluiter H. J., The H. Clinical characterization of non-small-cell lung cancer tumors showing neuroendocrine differentiation features. J Clin Oncol. 1989 Nov;7(11):1614–1620. doi: 10.1200/JCO.1989.7.11.1614. [DOI] [PubMed] [Google Scholar]
  5. Bostwick D. G., Roth K. A., Evans C. J., Barchas J. D., Bensch K. G. Gastrin-releasing peptide, a mammalian analog of bombesin, is present in human neuroendocrine lung tumors. Am J Pathol. 1984 Nov;117(2):195–200. [PMC free article] [PubMed] [Google Scholar]
  6. Brambilla E., Veale D., Moro D., Morel F., Dubois F., Brambilla C. Neuroendocrine phenotype in lung cancers. Comparison of immunohistochemistry with biochemical determination of enolase isoenzymes. Am J Clin Pathol. 1992 Jul;98(1):88–97. doi: 10.1093/ajcp/98.1.88. [DOI] [PubMed] [Google Scholar]
  7. Chejfec G., Lee I., Warren W. H., Gould V. E. Bombesin in human neuroendocrine (NE) neoplasms. Peptides. 1985;6 (Suppl 3):107–112. doi: 10.1016/0196-9781(85)90359-6. [DOI] [PubMed] [Google Scholar]
  8. Dhillon A. P., Rode J., Dhillon D. P., Moss E., Thompson R. J., Spiro S. G., Corrin B. Neural markers in carcinoma of the lung. Br J Cancer. 1985 May;51(5):645–652. doi: 10.1038/bjc.1985.97. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gazdar A. F., Zweig M. H., Carney D. N., Van Steirteghen A. C., Baylin S. B., Minna J. D. Levels of creatine kinase and its BB isoenzyme in lung cancer specimens and cultures. Cancer Res. 1981 Jul;41(7):2773–2777. [PubMed] [Google Scholar]
  10. Gould V. E., Wiedenmann B., Lee I., Schwechheimer K., Dockhorn-Dworniczak B., Radosevich J. A., Moll R., Franke W. W. Synaptophysin expression in neuroendocrine neoplasms as determined by immunocytochemistry. Am J Pathol. 1987 Feb;126(2):243–257. [PMC free article] [PubMed] [Google Scholar]
  11. Graziano S. L., Mazid R., Newman N., Tatum A., Oler A., Mortimer J. A., Gullo J. J., DiFino S. M., Scalzo A. J. The use of neuroendocrine immunoperoxidase markers to predict chemotherapy response in patients with non-small-cell lung cancer. J Clin Oncol. 1989 Oct;7(10):1398–1406. doi: 10.1200/JCO.1989.7.10.1398. [DOI] [PubMed] [Google Scholar]
  12. Hamid Q. A., Corrin B., Dewar A., Hoefler H., Sheppard M. N. Expression of gastrin-releasing peptide (human bombesin) gene in large cell undifferentiated carcinoma of the lung. J Pathol. 1990 Jun;161(2):145–151. doi: 10.1002/path.1711610209. [DOI] [PubMed] [Google Scholar]
  13. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  14. Kasurinen J., Syrjänen K. J. Peptide hormone immunoreactivity and prognosis in small-cell carcinoma of the lung. Respiration. 1986;49(1):61–67. doi: 10.1159/000194860. [DOI] [PubMed] [Google Scholar]
  15. Kayser K., Schmid W., Ebert W., Wiedenmann B. Expression of neuroendocrine markers (neuronspecific enolase, synaptophysin and bombesin) in carcinoma of the lung. Pathol Res Pract. 1988 Aug;183(4):412–417. doi: 10.1016/S0344-0338(88)80087-6. [DOI] [PubMed] [Google Scholar]
  16. Linnoila R. I., Mulshine J. L., Steinberg S. M., Funa K., Matthews M. J., Cotelingam J. D., Gazdar A. F. Neuroendocrine differentiation in endocrine and nonendocrine lung carcinomas. Am J Clin Pathol. 1988 Dec;90(6):641–652. doi: 10.1093/ajcp/90.6.641. [DOI] [PubMed] [Google Scholar]
  17. Mooi W. J., Dewar A., Springall D., Polak J. M., Addis B. J. Non-small cell lung carcinomas with neuroendocrine features. A light microscopic, immunohistochemical and ultrastructural study of 11 cases. Histopathology. 1988 Sep;13(3):329–337. doi: 10.1111/j.1365-2559.1988.tb02043.x. [DOI] [PubMed] [Google Scholar]
  18. Nakajima T., Shimosato Y., Morinaga S., Terasaki T., Tsumuraya M., Yamaguchi K., Ichinose H., Nagatsu T., Kato K., Nakazato Y. Immunohistochemical study of small cell lung carcinoma; with special reference to the neuroendocrine markers aromatic L-amino acid decarboxylase and gastrin-releasing peptide. Jpn J Clin Oncol. 1986 Sep;16(3):223–233. [PubMed] [Google Scholar]
  20. Said J. W., Vimadalal S., Nash G., Shintaku I. P., Heusser R. C., Sassoon A. F., Lloyd R. V. Immunoreactive neuron-specific enolase, bombesin, and chromogranin as markers for neuroendocrine lung tumors. Hum Pathol. 1985 Mar;16(3):236–240. doi: 10.1016/s0046-8177(85)80008-3. [DOI] [PubMed] [Google Scholar]
  21. Schmechel D., Marangos P. J., Brightman M. Neurone-specific enolase is a molecular marker for peripheral and central neuroendocrine cells. Nature. 1978 Dec 21;276(5690):834–836. doi: 10.1038/276834a0. [DOI] [PubMed] [Google Scholar]
  22. Schmechel D., Marangos P. J., Brightman M. Neurone-specific enolase is a molecular marker for peripheral and central neuroendocrine cells. Nature. 1978 Dec 21;276(5690):834–836. doi: 10.1038/276834a0. [DOI] [PubMed] [Google Scholar]
  23. Sheppard M. N. Neuroendocrine differentiation in lung tumours. Thorax. 1991 Nov;46(11):843–850. doi: 10.1136/thx.46.11.843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sundaresan V., Reeve J. G., Stenning S., Stewart S., Bleehen N. M. Neuroendocrine differentiation and clinical behaviour in non-small cell lung tumours. Br J Cancer. 1991 Aug;64(2):333–338. doi: 10.1038/bjc.1991.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Thompson R. J., Doran J. F., Jackson P., Dhillon A. P., Rode J. PGP 9.5--a new marker for vertebrate neurons and neuroendocrine cells. Brain Res. 1983 Nov 14;278(1-2):224–228. doi: 10.1016/0006-8993(83)90241-x. [DOI] [PubMed] [Google Scholar]
  26. Travis W. D., Linnoila R. I., Tsokos M. G., Hitchcock C. L., Cutler G. B., Jr, Nieman L., Chrousos G., Pass H., Doppman J. Neuroendocrine tumors of the lung with proposed criteria for large-cell neuroendocrine carcinoma. An ultrastructural, immunohistochemical, and flow cytometric study of 35 cases. Am J Surg Pathol. 1991 Jun;15(6):529–553. doi: 10.1097/00000478-199106000-00003. [DOI] [PubMed] [Google Scholar]
  27. Wiedenmann B., Franke W. W., Kuhn C., Moll R., Gould V. E. Synaptophysin: a marker protein for neuroendocrine cells and neoplasms. Proc Natl Acad Sci U S A. 1986 May;83(10):3500–3504. doi: 10.1073/pnas.83.10.3500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wilson B. S., Lloyd R. V. Detection of chromogranin in neuroendocrine cells with a monoclonal antibody. Am J Pathol. 1984 Jun;115(3):458–468. [PMC free article] [PubMed] [Google Scholar]
  29. Yamaguchi K., Abe K., Adachi I., Kimura S., Suzuki M., Shimada A., Kodama T., Kameya T., Shimosato Y. Peptide hormone production in primary lung tumors. Recent Results Cancer Res. 1985;99:107–116. doi: 10.1007/978-3-642-82533-0_12. [DOI] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES