Cytoplasmic OCT4 staining is a sensitive marker of neuroendocrine differentiation

Previous studies by the authors have described a novel cytoplasmic staining pattern with OCT4 in normal adrenal medullary tissue and in paragangliomas. We aimed to determine if this type of staining is found in other neuroendocrine tissues by examining a broad range of neuroendocrine tumors. Fifty neuroendocrine tumors of various grades and primary organ sites were selected. All cases were immunostained with OCT4 and Ki-67. OCT4 reactivity was then scored for intensity (0-3+) and extent (0-3+). Ki-67 proliferation index was scored as a percentage of total tumor cells. Immunoelectron microscopy was performed to determine precise location of antibody binding within cells. Immunoreactivity was seen in 26 (96%) of 27 cases of carcinoid tumors. The same type of strong staining was seen in 4 (67%) of 6 moderately differentiated neuroendocrine tumors. Only 2 (12%) of 17 poorly differentiated neuroendocrine tumors showed similar staining. A strong, inverse correlation was seen with OCT4 and Ki-67 index. Immunoelectron microscopy showed binding of OCT4 antibody to neurosecretory granules. Cytoplasmic staining of OCT4 is a sensitive marker of neuroendocrine differentiation that has yet to be described in any other tissue or tumor type. These findings show that this antibody has a high affinity for well- to moderately differentiated neuroendocrine tumors. Although comparative studies with other markers and a more extensive analysis of other tissue types are necessary, cytoplasmic staining of OCT4 may prove to be a useful immunostain in the diagnosis of neuroendocrine tumors.