Synaptophysin and chromogranin A expression analysis in human tumors
Ria Uhlig, David Dum, Natalia Gorbokon, Anne Menz, Franziska Büscheck, Andreas M. Luebke, Claudia Hube‐Magg, Andrea Hinsch, Doris Höflmayer, Christoph Fraune, Katharina Möller, Christian Bernreuther, Patrick Lebok, Sören Weidemann, Maximilian Lennartz, Frank Jacobsen, Till S. Clauditz, Guido Sauter, Waldemar Wilczak, Stefan Steurer, Eike Burandt, Rainer Krech, Till Krech, Andreas H. Marx, Ronald Simon, Sarah Minner
Abstract
The expression of the neuroendocrine markers synaptophysin and chromogranin A was analyzed by immunohistochemistry in 14,584 samples from 103 different tumor types and subtypes in a tissue microarray format. At least one of these markers was found to be positive in 96.7% of tumors from various subtypes of neuroendocrine neoplasms. In non-neuroendocrine tumors, synaptophysin and/or chromogranin A staining was seen in 6.3% (n = 584), specifically in 41 of 88 non-neuroendocrine tumor entities. Basal cell carcinomas of the skin (50% positive for chromogranin A alone) and adrenocortical carcinomas (91.7% positive for synaptophysin alone) stood out due to a frequent expression of only one specific marker. A subdivision of non-neuroendocrine neoplasms revealed "neuroendocrine differentiation" most commonly in adenocarcinomas from the female genital tract (18.9%), from pancreatico-/hepato-/biliary tract (15.8%) and the prostate (14.9%) while it was rare in urothelial (1.0%) and squamous cell carcinomas (0.6%). A comparison with clinico-pathological parameters of tumor aggressiveness did not suggest a clinical significance of neuroendocrine marker expression in 204 endometrium cancers, 249 pancreatic adenocarcinomas, 233 gastric adenocarcinomas and 1,182 colorectal adenocarcinomas. Within a cohort of 1,073 breast cancers of no special type, synaptophysin positivity was seen in 4.9% of cases and it was significantly linked to advanced tumor stage (p = 0.0427), high tumor grade (p = 0.0319) and loss of estrogen receptor expression (p = 0.0061) but unrelated to patient outcome. In conclusion, "neuroendocrine differentiation" can be observed in many different tumor types with non-neuroendocrine morphology. Evidence for a statistically significant association (p < 0.0001) between such a "neuroendocrine differentiation" and tumor aggressiveness could not be found.