# The Expression of Neuroendocrine Markers in a Small Subset of Ameloblastoma with Implications of Clusterin

## TL;DR

This study explores neuroendocrine markers in ameloblastoma, finding that some cases show signs of neuroendocrine differentiation, possibly linked to clusterin expression.

## Contribution

The first study to suggest neuroendocrine differentiation in ameloblastoma using SYP and INSM1 immunoexpression and dense-core granules.

## Key findings

- SYP and INSM1 immunoexpression and dense-core granules suggest neuroendocrine differentiation in ameloblastoma.
- SYP-positive cases were exclusively found in CD56- and CLU-positive cases, with significant correlation between SYP and CLU expression.
- CD56 expression correlates with older age but not with subtype, SYP, or CLU expression.

## Abstract

Immunohistochemically, ameloblastomas often express CD56; however, novel neuroendocrine markers such as synaptophysin (SYP), insulinoma-associated protein 1 (INSM1), and chromogranin A (CgA) remain unexplored. We analyzed 36 ameloblastoma specimens for CD56, SYP, CgA, and clusterin (CLU) and examined limited samples for INSM1 expression by performing immunohistochemistry, transmission electron microscopy, and reverse transcriptase-polymerase chain reaction. Our findings indicate that the limited cells were positive for CD56, SYP, CgA, INSM1, and CLU expression in 72% (26/36), 14% (5/36), 0% (0/40), 80% (4/5), and 22% (8/36) of the cases, respectively. CD56 expression correlated with older age, but not with subtype, SYP, and CLU expression. However, SYP-positive cases were exclusively found in CD56- and CLU-positive cases, and SYP and CLU expression were significantly correlated. Selected cases had dense-core granules and NCAM1 and SYP mRNA expression. This study is the first to suggest neuroendocrine differentiation in ameloblastomas, as indicated by SYP and INSM1 immunoexpression and the presence of dense-core granules, which are consistent with the recent World Health Organization classification of Head and Neck Tumors guidelines. SYP-positive and CgA-negative phenotypes may characterize neuroendocrine differentiation in ameloblastoma. Although the underlying molecular mechanism remains unclear, CLU expression may be associated with neuroendocrine differentiation.