Abstract
Gastrointestinal cancers have frequently shown neuroendocrine (NE) differentiation, but whether NE differentiation occurs in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, tissue sections obtained from 43 patients with ESCC from a high-incidence area of Northern China were used for the assessing of NE differentiation by immunohistochemistry using antibody against chromogranin A (CGA). In addition, the malignant characteristics and proliferation capacity of CGA-positive cells were also examined by immunohistochemistry. The clinicopathological significance of these CGA-positive tumor cells in ESCC was assessed. Of 43 ESCC samples, CGA-immunoreactive tumor cells were detected in 10 cases (23.26%). However, the CGA-positive tumor cells were scattered at a very low number among non-immunoreactive tumor cells and were rarely constituted a major part of cancer cell nests. Only 4.65% (2/43) cases showed a high density (>10 cells but <1% of total tumor cell mass) of CGA-positive tumor cells. P53 immunoreactivity was frequently shown, while Ki67 was hard to detect in these CGA-positive cells. In addition, no relationship between CGA positivity rate and clinicopathological parameters was found. Thus, we concluded that low-density CGA-positive tumor cells can be detected in ESCC, supporting the notion that heterogeneous NE differentiation also exists in tumors that lack neuroendocrine cells in their normal epithelial counterparts.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Barrett P, Hobbs RC, Coates PJ, et al: Endocrine cells of the human gastrointestinal tract have no proliferative capacity. Histochem J 27:482–486, 1995
Blumenfeld W, Chandhoke DK, Sagerman P, et al: Neuroendocrine differentiation in gastric adenocarcinomas. An immunohistochemical study. Arch Pathol Lab Med 120:478–481, 1996
Bosman FT: Neuroendocrine cells in non-endocrine tumors: what does it mean? Verh Dtsch Ges Pathol 81:62–72, 1997
Bosman FT, Louwerens JW: Neuroendocrine (APUD) cells in ovarian teratomas and testicular teratocarcinomas. Cell Biol Int Rep 5:464, 1981
Chang KT, Huang CY, Tsai CM, et al: Role of IL-6 in neuroendocrine differentiation and chemosensitivity of non-small cell lung cancer. Am J Physiol Lung Cell Mol Physiol 289:L438–445, 2005
Cho KJ, Jang JJ, Lee SS, et al: Basaloid squamous carcinoma of the oesophagus: a distinct neoplasm with multipotential differentiation. Histopathology 36:331–340, 2000
Cui G, Koh TJ, Chen D, et al: Overexpression of glycine-extended gastrin inhibits parietal cell loss and atrophy in the mouse stomach. Cancer Res 64:8160–8166, 2004
de Bruine AP, Dinjens WN, van der Linden EP, et al: Extracellular matrix components induce endocrine differentiation in vitro in NCI-H716 cells. Am J Pathol 142:773–782, 1993
Hamilton K, Chiappori A, Olson S, et al: Prevalence and prognostic significance of neuroendocrine cells in esophageal adenocarcinoma. Mod Pathol 13:475–481, 2000
Hayashi H, Ooi A, Nakanishi I: Biological and clinicopathological significance of endocrine differentiation of gastric adenocarcinoma evaluated by double immunohistochemical labeling for chromogranin A and bromodeoxyuridine. Jpn J Clin Oncol 20:339–348, 1990
Jaskiewicz K, Louw J, Anichkov N: Barrett’s oesophagus: mucin composition, neuroendocrine cells, p53 protein, cellular proliferation and differentiation. Anticancer Res 14:1907–1912, 1994
Li MX, Cheng SJ: Carcinogenesis of esophageal cancer in Linxian, China. Chin Med J (Engl) 97:311–313, 1984
Li Z, Shimada Y, Uchida S, et al: TGF-alpha as well as VEGF, PD-ECGF and bFGF contribute to angiogenesis of esophageal squamous cell carcinoma. Int J Oncol 17:453–460, 2000
Linder S, Myrvold K, Falkmer UG, et al: Neuroendocrine cells in pancreatic duct adenocarcinoma: an immunohistochemical study. J Exp Clin Cancer Res 25:213–221, 2006
Louwerens JK, Schaberg A, Bosman FT: Neuroendocrine cells in cystic mucinous tumours of the ovary. Histopathology 7:389–398, 1983
Lu SH, Zhou Y, Que HP, et al: Peptidergic innervation of human esophageal and cardiac carcinoma. World J Gastroenterol 9:399–403, 2003
Ohashi K, Nemoto T, Nakamura K, et al: Increased expression of matrix metalloproteinase 7 and 9 and membrane type 1-matrix metalloproteinase in esophageal squamous cell carcinomas. Cancer 88:2201–2209, 2000
Ooi A, Hayashi H, Katsuda S, et al: Gastric carcinoma cells with endocrine differentiation show no evidence of proliferation. Hum Pathol 23:736–741, 1992
Ooi A, Mai M, Ogino T, et al: Endocrine differentiation of gastric adenocarcinoma. The prevalence as evaluated by immunoreactive chromogranin A and its biologic significance. Cancer 62:1096–1104, 1988
Parkin DM, Bray FI, Devesa SS: Cancer burden in the year 2000. The global picture. Eur J Cancer 37 Suppl 8):S4-S66, 2001
Rengifo-Cam W, Singh P: Role of progastrins and gastrins and their receptors in GI and pancreatic cancers: targets for treatment. Curr Pharm Des 10:2345–2358, 2004
Seifert P, Spitznas M: Tumours may be innervated. Virchows Arch 438:228, 2001
Syversen U, Halvorsen T, Marvik R, et al: Neuroendocrine differentiation in colorectal carcinomas. Eur J Gastroenterol Hepatol 7:667–674, 1995
Szumilo J, Swatek J, Chroscicki A, et al: Colonic adenocarcinoma with numerous paneth and endocrine cells. Pol J Pathol 56:89–92, 2005
Tajima Y, Nakajima T, Sugano I, et al: Hepatocellular carcinoma containing endocrine cells. An autopsy report of triple cancer involving the liver, kidney and thyroid. Acta Pathol Jpn 42:904–910, 1992
Tezel E, Nagasaka T, Tezel G, et al: Characterization of scattered neuroendocrine cells in ductal carcinoma of the pancreas. Pancreas 25:136–141, 2002
Untergasser G, Plas E, Pfister G, et al: Interferon-gamma induces neuroendocrine-like differentiation of human prostate basal-epithelial cells. Prostate 64:419–429, 2005
Waldum HL, Brenna E: Non-proliferative capacity of endocrine cells of the human gastro-intestinal tract. Histochem J 28:397–398, 1996
Wang JH, Dhillon AP, Sankey EA, et al: ‘Neuroendocrine’ differentiation in primary neoplasms of the liver. J Pathol 163:61–67, 1991
Wang KL, Yang Q, Cleary KR, et al: The significance of neuroendocrine differentiation in adenocarcinoma of the esophagus and esophagogastric junction after preoperative chemoradiation. Cancer 107:1467–1474, 2006
Wang LS, Chow KC, Wu CW: Expression and up-regulation of interleukin-6 in oesophageal carcinoma cells by n-sodium butyrate. Br J Cancer 80:1617–1622, 1999
Zhao M, Laissue JA, Zimmermann A: “Neuroendocrine” differentiation in hepatocellular carcinomas (HCCs): immunohistochemical reactivity is related to distinct tumor cell types, but not to tumor grade. Histol Histopathol 8:617–626, 1993
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yuan, A., Liu, J., Liu, Y. et al. Chromogranin A-positive tumor cells in human esophageal squamous cell carcinomas. Pathol. Oncol. Res. 13, 321–325 (2007). https://doi.org/10.1007/BF02940311
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02940311