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. 1990 Feb;136(2):319–327.

Chromogranin A and B gene expression in carcinomas of the breast. Correlation of immunocytochemical, immunoblot, and hybridization analyses.

A Pagani 1, M Papotti 1, H Höfler 1, R Weiler 1, H Winkler 1, G Bussolati 1
PMCID: PMC1877399  PMID: 2305832

Abstract

Chromogranins (Cg) are regarded as specific neuroendocrine (NE) markers in cells and tumors. Expression of CgA and CgB genes has been demonstrated by correlative immunocytochemical, immunoblotting, in situ hybridization, and Northern blot procedures in seven argyrophilic breast carcinomas, while eight control cases of ductal carcinomas, not otherwise specified, were negative. A high degree of correlation was observed between the various techniques revealing CgA and/or CgB gene expression at different levels; minor discrepancies might be related to tumor heterogeneity or to technical factors. The present study, confirming previous investigations, establishes NE differentiation in a group of human breast cancers. The identification of this type of tumors, especially by testing chromogranin(s) production, appears to be of both biologic and clinical interest.

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Selected References

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

  1. Ahn T. G., Cohn D. V., Gorr S. U., Ornstein D. L., Kashdan M. A., Levine M. A. Primary structure of bovine pituitary secretory protein I (chromogranin A) deduced from the cDNA sequence. Proc Natl Acad Sci U S A. 1987 Jul;84(14):5043–5047. doi: 10.1073/pnas.84.14.5043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Azzopardi J. G., Muretto P., Goddeeris P., Eusebi V., Lauweryns J. M. 'Carcinoid' tumours of the breast: the morphological spectrum of argyrophil carcinomas. Histopathology. 1982 Sep;6(5):549–569. doi: 10.1111/j.1365-2559.1982.tb02750.x. [DOI] [PubMed] [Google Scholar]
  3. Benedum U. M., Baeuerle P. A., Konecki D. S., Frank R., Powell J., Mallet J., Huttner W. B. The primary structure of bovine chromogranin A: a representative of a class of acidic secretory proteins common to a variety of peptidergic cells. EMBO J. 1986 Jul;5(7):1495–1502. doi: 10.1002/j.1460-2075.1986.tb04388.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Benedum U. M., Lamouroux A., Konecki D. S., Rosa P., Hille A., Baeuerle P. A., Frank R., Lottspeich F., Mallet J., Huttner W. B. The primary structure of human secretogranin I (chromogranin B): comparison with chromogranin A reveals homologous terminal domains and a large intervening variable region. EMBO J. 1987 May;6(5):1203–1211. doi: 10.1002/j.1460-2075.1987.tb02355.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Burnette W. N. "Western blotting": electrophoretic transfer of proteins from sodium dodecyl sulfate--polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem. 1981 Apr;112(2):195–203. doi: 10.1016/0003-2697(81)90281-5. [DOI] [PubMed] [Google Scholar]
  6. Bussolati G., Gugliotta P., Sapino A., Eusebi V., Lloyd R. V. Chromogranin-reactive endocrine cells in argyrophilic carcinomas ("carcinoids") and normal tissue of the breast. Am J Pathol. 1985 Aug;120(2):186–192. [PMC free article] [PubMed] [Google Scholar]
  7. Bussolati G., Papotti M., Sapino A., Gugliotta P., Ghiringhello B., Azzopardi J. G. Endocrine markers in argyrophilic carcinomas of the breast. Am J Surg Pathol. 1987 Apr;11(4):248–256. doi: 10.1097/00000478-198704000-00002. [DOI] [PubMed] [Google Scholar]
  8. Capella C., Eusebi V., Mann B., Azzopardi J. G. Endocrine differentiation in mucoid carcinoma of the breast. Histopathology. 1980 Nov;4(6):613–630. doi: 10.1111/j.1365-2559.1980.tb02957.x. [DOI] [PubMed] [Google Scholar]
  9. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  10. Clayton F., Sibley R. K., Ordonez N. G., Hanssen G. Argyrophilic breast carcinomas: evidence of lactational differentiation. Am J Surg Pathol. 1982 Jun;6(4):323–333. doi: 10.1097/00000478-198206000-00005. [DOI] [PubMed] [Google Scholar]
  11. Cohle S. D., Tschen J. A., Smith F. E., Lane M., McGavran M. H. ACTH-secreting carcinoma of the breast. Cancer. 1979 Jun;43(6):2370–2376. doi: 10.1002/1097-0142(197906)43:6<2370::aid-cncr2820430630>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
  12. Cross A. S., Azzopardi J. G., Krausz T., van Noorden S., Polak J. M. A morphological and immunocytochemical study of a distinctive variant of ductal carcinoma in-situ of the breast. Histopathology. 1985 Jan;9(1):21–37. doi: 10.1111/j.1365-2559.1985.tb02968.x. [DOI] [PubMed] [Google Scholar]
  13. FEYRTER F., HARTMANN G. UBER DIE CARCINOIDE WUCHSFORM DES CARCINOMA MAMMAE, INSBESONDERE DAS CARCINOMA SOLIDUM (GELATINOSUM) MAMMAE. Frankf Z Pathol. 1963 Oct 3;73:24–39. [PubMed] [Google Scholar]
  14. Ferguson D. J., Anderson T. J. Distribution of dense core granules in normal, benign and malignant breast tissue. J Pathol. 1985 Sep;147(1):59–65. doi: 10.1002/path.1711470108. [DOI] [PubMed] [Google Scholar]
  15. Fischer-Colbrie R., Frischenschlager I. Immunological characterization of secretory proteins of chromaffin granules: chromogranins A, chromogranins B, and enkephalin-containing peptides. J Neurochem. 1985 Jun;44(6):1854–1861. doi: 10.1111/j.1471-4159.1985.tb07179.x. [DOI] [PubMed] [Google Scholar]
  16. Fischer-Colbrie R., Iacangelo A., Eiden L. E. Neural and humoral factors separately regulate neuropeptide Y, enkephalin, and chromogranin A and B mRNA levels in rat adrenal medulla. Proc Natl Acad Sci U S A. 1988 May;85(9):3240–3244. doi: 10.1073/pnas.85.9.3240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Fisher E. R., Palekar A. S. Solid and mucinous varieties of so-called mammary carcinoid tumors. Am J Clin Pathol. 1979 Dec;72(6):909–916. doi: 10.1093/ajcp/72.6.909. [DOI] [PubMed] [Google Scholar]
  18. Grimelius L. A silver nitrate stain for alpha-2 cells in human pancreatic islets. Acta Soc Med Ups. 1968;73(5-6):243–270. [PubMed] [Google Scholar]
  19. Hagn C., Schmid K. W., Fischer-Colbrie R., Winkler H. Chromogranin A, B, and C in human adrenal medulla and endocrine tissues. Lab Invest. 1986 Oct;55(4):405–411. [PubMed] [Google Scholar]
  20. Helman L. J., Gazdar A. F., Park J. G., Cohen P. S., Cotelingam J. D., Israel M. A. Chromogranin A expression in normal and malignant human tissues. J Clin Invest. 1988 Aug;82(2):686–690. doi: 10.1172/JCI113648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Heyderman E., Neville A. M. A shorter immunoperoxidase technique for the demonstration of carcinoembryonic antigen and other cell products. J Clin Pathol. 1977 Feb;30(2):138–140. doi: 10.1136/jcp.30.2.138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hoefler H., Childers H., Montminy M. R., Lechan R. M., Goodman R. H., Wolfe H. J. In situ hybridization methods for the detection of somatostatin mRNA in tissue sections using antisense RNA probes. Histochem J. 1986 Nov-Dec;18(11-12):597–604. doi: 10.1007/BF01675295. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Iacangelo A., Affolter H. U., Eiden L. E., Herbert E., Grimes M. Bovine chromogranin A sequence and distribution of its messenger RNA in endocrine tissues. Nature. 1986 Sep 4;323(6083):82–86. doi: 10.1038/323082a0. [DOI] [PubMed] [Google Scholar]
  25. Iacangelo A., Okayama H., Eiden L. E. Primary structure of rat chromogranin A and distribution of its mRNA. FEBS Lett. 1988 Jan 25;227(2):115–121. doi: 10.1016/0014-5793(88)80880-9. [DOI] [PubMed] [Google Scholar]
  26. Kaneko H., Hojo H., Ishikawa S., Yamanouchi H., Sumida T., Saito R. Norepinephrine-producing tumors of bilateral breasts: a case report. Cancer. 1978 May;41(5):2002–2007. doi: 10.1002/1097-0142(197805)41:5<2002::aid-cncr2820410547>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  27. Krenning E. P., Bakker W. H., Breeman W. A., Koper J. W., Kooij P. P., Ausema L., Lameris J. S., Reubi J. C., Lamberts S. W. Localisation of endocrine-related tumours with radioiodinated analogue of somatostatin. Lancet. 1989 Feb 4;1(8632):242–244. doi: 10.1016/s0140-6736(89)91258-0. [DOI] [PubMed] [Google Scholar]
  28. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  29. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  30. Lloyd R. V., Iacangelo A., Eiden L. E., Cano M., Jin L., Grimes M. Chromogranin A and B messenger ribonucleic acids in pituitary and other normal and neoplastic human endocrine tissues. Lab Invest. 1989 Apr;60(4):548–556. [PubMed] [Google Scholar]
  31. Lloyd R. V., Wilson B. S. Specific endocrine tissue marker defined by a monoclonal antibody. Science. 1983 Nov 11;222(4624):628–630. doi: 10.1126/science.6635661. [DOI] [PubMed] [Google Scholar]
  32. Nesland J. M., Holm R., Johannessen J. V. A study of different markers for neuroendocrine differentiation in breast carcinomas. Pathol Res Pract. 1986 Oct;181(5):524–530. doi: 10.1016/S0344-0338(86)80144-3. [DOI] [PubMed] [Google Scholar]
  33. Nesland J. M., Holm R., Johannessen J. V., Gould V. E. Neuroendocrine differentiation in breast lesions. Pathol Res Pract. 1988 Apr;183(2):214–221. doi: 10.1016/S0344-0338(88)80048-7. [DOI] [PubMed] [Google Scholar]
  34. O'Farrell P. H. High resolution two-dimensional electrophoresis of proteins. J Biol Chem. 1975 May 25;250(10):4007–4021. [PMC free article] [PubMed] [Google Scholar]
  35. Papotti M., Macrì L., Finzi G., Capella C., Eusebi V., Bussolati G. Neuroendocrine differentiation in carcinomas of the breast: a study of 51 cases. Semin Diagn Pathol. 1989 May;6(2):174–188. [PubMed] [Google Scholar]
  36. Papotti M., Macrí L., Bussolati G., Reubi J. C. Correlative study on neuro-endocrine differentiation and presence of somatostatin receptors in breast carcinomas. Int J Cancer. 1989 Mar 15;43(3):365–369. doi: 10.1002/ijc.2910430302. [DOI] [PubMed] [Google Scholar]
  37. Rindi G., Buffa R., Sessa F., Tortora O., Solcia E. Chromogranin A, B and C immunoreactivities of mammalian endocrine cells. Distribution, distinction from costored hormones/prohormones and relationship with the argyrophil component of secretory granules. Histochemistry. 1986;85(1):19–28. doi: 10.1007/BF00508649. [DOI] [PubMed] [Google Scholar]
  38. Schmid K. W., Fischer-Colbrie R., Hagn C., Jasani B., Williams E. D., Winkler H. Chromogranin A and B and secretogranin II in medullary carcinomas of the thyroid. Am J Surg Pathol. 1987 Jul;11(7):551–556. doi: 10.1097/00000478-198707000-00007. [DOI] [PubMed] [Google Scholar]
  39. Schmid K. W., Weiler R., Xu R. W., Hogue-Angeletti R., Fischer-Colbrie R., Winkler H. An immunological study on chromogranin A and B in human endocrine and nervous tissues. Histochem J. 1989 Jun;21(6):365–373. doi: 10.1007/BF01798500. [DOI] [PubMed] [Google Scholar]
  40. Schober M., Fischer-Colbrie R., Schmid K. W., Bussolati G., O'Connor D. T., Winkler H. Comparison of chromogranins A, B, and secretogranin II in human adrenal medulla and pheochromocytoma. Lab Invest. 1987 Oct;57(4):385–391. [PubMed] [Google Scholar]
  41. Simon J. P., Bader M. F., Aunis D. Secretion from chromaffin cells is controlled by chromogranin A-derived peptides. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1712–1716. doi: 10.1073/pnas.85.5.1712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Smith A. D., Winkler H. A simple method for the isolation of adrenal chromaffin granules on a large scale. Biochem J. 1967 May;103(2):480–482. doi: 10.1042/bj1030480. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Sobol R. E., Memoli V., Deftos L. J. Hormone-negative, chromogranin A-positive endocrine tumors. N Engl J Med. 1989 Feb 16;320(7):444–447. doi: 10.1056/NEJM198902163200707. [DOI] [PubMed] [Google Scholar]
  44. Taxy J. B., Tischler A. S., Insalaco S. J., Battifora H. "Carcinoid" tumor of the breast. A variant of conventional breast cancer? Hum Pathol. 1981 Feb;12(2):170–179. doi: 10.1016/s0046-8177(81)80104-9. [DOI] [PubMed] [Google Scholar]
  45. Weiler R., Feichtinger H., Schmid K. W., Fischer-Colbrie R., Grimelius L., Cedermark B., Papotti M., Bussolati G., Winkler H. Chromogranin A and B and secretogranin II in bronchial and intestinal carcinoids. Virchows Arch A Pathol Anat Histopathol. 1987;412(2):103–109. doi: 10.1007/BF00716181. [DOI] [PubMed] [Google Scholar]
  46. Weiler R., Fischer-Colbrie R., Schmid K. W., Feichtinger H., Bussolati G., Grimelius L., Krisch K., Kerl H., O'Connor D., Winkler H. Immunological studies on the occurrence and properties of chromogranin A and B and secretogranin II in endocrine tumors. Am J Surg Pathol. 1988 Nov;12(11):877–884. doi: 10.1097/00000478-198811000-00008. [DOI] [PubMed] [Google Scholar]
  47. Winkler H., Apps D. K., Fischer-Colbrie R. The molecular function of adrenal chromaffin granules: established facts and unresolved topics. Neuroscience. 1986 Jun;18(2):261–290. doi: 10.1016/0306-4522(86)90154-5. [DOI] [PubMed] [Google Scholar]
  48. Woodard B. H., Eisenbarth G., Wallace N. R., Mossler J. A., McCarty K. S., Jr Adrenocorticotropin production by a mammary carcinoma. Cancer. 1981 Apr 1;47(7):1823–1827. doi: 10.1002/1097-0142(19810401)47:7<1823::aid-cncr2820470717>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]

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