Abstract
Colorectal adenocarcinomas may display features of endocrine differentiation, shown by argyrophil stains and by the expression of endocrine markers such as chromogranin A. We investigated chromogranin A and secretogranin II immunoreactivity in a series of 208 carcinomas of the large bowel to assess the prevalence and clinical significance of endocrine differentiation. Tumours expressing endocrine markers were classified as low expressors (< than 1 immunoreactive tumour cell/mm2) and high expressors (> than 1 immunoreactive tumour cell/mm2). There were 33 (16%) carcinomas showing both chromogranin A and secretogranin II immunoreactivity: 11 tumours (5%) were high expressors. Endocrine differentiation was not related to the disease stage, tumour location, grade, DNA ploidy and p53 protein accumulation. In the entire series chromogranin A immunoreactivity did not provide prognostic information using univariate and multivariate analysis. A worse overall survival (P=0.048) was demonstrated for the stage III patients with high expressor tumours, but there were only five patients in this group. The results of our investigation suggest that chromogranin A immunoreactivity is not a useful variable in the prognostic assessment of colorectal adenocarcinomas.
Similar content being viewed by others
References
Arends JW, Wiggers T, Verstijnen K, Bosman FT (1986) The occurrence and clinicopathological significance of serotonin immunoreactive cells in large bowel carcinoma. J Pathol 149:97–102
Azzopardi JG, Pollock DJ (1963) Argentaffin and argyrophils cells in gastric carcinoma. J Pathol Bacteriol 86:443–452
Beahrs OH, Henson DE, Hutter RVP, Meyers MH (1988) Manual for staging of cancer, 3rd edn. JB Lippincott, Philadelphia
Bonar SF, Sweeney EC (1986) The prevalence, prognostic significance and hormonal content of endocrine cells in gastric cancer. Histopathology 10:53–63
Bosari S, Lee AKC, Wiley BD, Heatley GJ, Hamilton WM, Silverman ML (1992) DNA quantitation by image analysis of paraffin-embedded colorectal adenocarcinomas and its prognostic value. Mod Pathol 5:324–328
Bosari S, Lee AKC, DeLellis RA, Wiley BD, Heatley GJ, Silverman ML (1992) Microvessel quantitation and prognosis in invasive carcinoma. Hum Pathol 23:755–761
Bosari S, Viale G, Bossi P, Maggioni M, Coggi G, Murray JJ, Lee AKC (1994) Cytoplasmic accumulation of p53 protein: an independent prognostic indicator in colorectal adenocarcinomas. J Natl Cancer Inst 86:681–687
Bruine AP de, Dinjens WNM, Van der Linden EP, Pijls MMJ, Moerkerk PT, Bosman FT (1993) Extracellular matrix components induce endocrine differentiation in vitro in NCI-H716 cells. Am J Pathol 142:773–782
Bruine AP de, Wiggers T, Beek C, Volovics A, Meyenfeldt M von, Arends JW, Bosman FT (1993) Endocrine cells in colorectal adenocarcinomas: incidence, hormone profile and prognostic relevance. Int J Cancer 54:765–771
Campo E, Munoz J, Miquel R, Palacin A, Cardesa A, Sloane BF, Emmert-Buck MR (1994) Cathepsin B expression in colorectal carcinomas correlates with tumor progression and shortened patient survival. Am J Pathol 145:301–309
Cox WF, Pierce GB (1982) The endodermal origin of the endocrine cells of an adenocarcinoma of the colon of the rat. Cancer 50:1530–1538
Eiden LE, Huttner WB, Mallet J, O'Connor DT, Winkler H, Zanini A (1987) A nomenclature proposal for the chromogranin/secretogranins proteins. Neuroscience 21:1019–1021
Facer P, Bishop AE, Lloyd RV, Wilson BS, Hennessy RJ, Polak JM (1985) Chromogranin: a newly recognized marker for endocrine cells of the human gastrointestinal tract. Gastroenterology 89:1366–1373
Folkman J, Klagsbrun M (1987) Angiogenic factors. Science 235:442–447
Hamada Y, Oishi A, Shoji T, Takada H, Yamamura M, Hioki K, Yamamoto M (1992) Endocrine cells and prognosis in patients with colorectal carcinoma. Cancer 69:2641–2646
Hu SM, Raine L, Fanger H (1981) Use of avidin-biotin-peroxidase complex (ABC): a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29:577–580
Hynes RO (1987) Integrins: a family of cell surface receptors. Cell 48:549–554
Iwashita A (1979) Argyrophil and argentaffin cells in carcinomas of the colon and rectum. Fukuoka Igaku Zasshi 70:370–390
Jansson D, Gould VE, Gooch GT, Rittenhouse HG, Shin SS, Manderino GL, Tomita JT, Staren ED (1988) Immunohistochemical analysis of colon carcinomas applying exocrine and neuroendocrine markers. APMIS 96:1129–1139
Kandel J, Bossy-Wetzel E, Radvanyi F, Klagsbrun M, Folkman J, Hanahan D (1991) Neovascularization is associated with a switch to the export of bFGF in the multistep development of fibrosarcoma. Cell 66:1095–1104
Kirkland SC (1988) Clonal origin of columnar, mucous and endocrine cell lineages in human colorectal epithelium. Cancer 61:1359–1363
Koretz K, Schlag P, Boumsell L, Moller P (1991) Expression of VLA-α2, VLA-α6, and VLA-β1 chains in normal mucosa and adenomas of the colon, and in colon carcinomas and their liver metastases. Am J Pathol 138:741–750
Kubo T, Watanabe H (1971) Neoplastic argentaffin cells in gastric and intestinal carcinomas. Cancer 27:447–454
Le Douarin NM, Teillet MA (1973) The migration of neural crest cells to the wall of the digestive tract in avian embryo. J Embryol Exp Morphol 30:31–48
Li D, Bell J, Brown A, Berry CL (1994) The observation of angiogenin and basic fibroblast growth factor gene expression in human colonic adenocarcinomas, gastric adenocarcinomas and hepatocellular carcinomas. J Pathol 172:171–175
Macchiarini P, Fontanini G, Hardin MJ, Squartini F, Angeletti CA (1992) Relation of neovasculature to metastases of non-small-cell lung cancer. Lancet 340:145–146
O'Connor DT, Burton D, Deftos LJ (1983) Immunoreactive human chromogranin-A in diverse polypeptide-hormone-producing human tumors and normal endocrine tissues. J Clin Endocrinol Metab 57:1084–1086
Ooi A, Mai M, Ogino T, Ueda H, Kitamura T, Takahashi Y, Kawahara E, Nakanishi I (1988) Endocrine differentiation of gastric adenocarcinoma. The prevalence as evaluated by immunoreactive chromogranin A and its biologic significance. Cancer 62:1096–1104
Pearse AGE (1969) The cytochemistry and ultrastructure of polypeptide hormone-producing cells of the APUD series, and the embryologic, physiologic and pathologic implications of the concept. J Histochem Cytochem 17:303–313
Pelagi M, Bisiani C, Gini A, Bonardi MA, Rosa P, Mare P, Viale G, Cozzi MG, Salvadore M, Zanini A, Siccardi AG, Buffa R (1989) Preparation and characterization of anti-human chromogranin A and chromogranin B (secretogranin I) monoclonal antibodies. Mol Cell Probes 4:87–101
Pelagi M, Zanini A, Gasparri A, Ermellino L, Giudici AM, Ferrero S, Siccardi AG, Buffa R (1992) Immunodetection of secretogranin II in animal and human tissues by new monoclonal antibodies. Regul Pept 39:201–214
Rogers LW, Murphy RC (1979) Gastric carcinoid and gastric carcinoma. Am J Surg Pathol 3:195–202
Ruoslahti E, Pierschbacher MD (1987) New perspective in cell adhesion: RGD and integrins. Science 238:491–497
Smith DM, Haggitt RC (1984) The prevalence and prognostic significance of argyrophil cells in colorectal carcinomas. Am J Surg Pathol 8:123–128
Sun X-F, Carstersen JM, Zhang H, Stal O, Wingren S, Hatschek T, Nordenskjold B (1992) Prognostic significance of cytoplasmic p53 oncoprotein in colorectal adenocarcinoma. Lancet 340:1369–1373
Tahara E, Haizuka S, Kodama T, Yamada A (1975) The relationship of gastrointestinal endocrine cells to gastric epithelial changes with special reference to gastric cancer. Acta Pathol Jpn 25:161–177
Weidner N, Folkman J, Pozza F, Bevilacqua P, Allred EN, Moore DH, Meli S, Gasparini G (1992) Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst 84:1875–1887
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ferrero, S., Buffa, R., Pruneri, G. et al. The prevalence and clinical significance of chromogranin A and secretogranin II immunoreactivity in colorectal adenocarcinomas. Vichows Archiv A Pathol Anat 426, 587–592 (1995). https://doi.org/10.1007/BF00192113
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00192113