Comparison between NOR-1 and DOG-1 immunohistochemistry staining in the diagnosis of salivary acinic cell carcinoma

Introduction

Acinic cell carcinoma (ACC) of the salivary gland presents diagnostic challenges due to its wide histomorphological variability. DOG-1 has been shown to be sensitive in the diagnosis of ACC but is not specific. DOG-1 positivity can be seen in normal salivary acini, polymorphous adenocarcinoma, and luminal cells of pleomorphic adenoma. A novel rearrangement t(4;9) (q13;q31) leading to the upregulation of nuclear receptor subfamily 4 group A member 3 (NR4A3) has recently been identified in ACC. Immunostaining using an antibody targeting this rearrangement, neuron-derived orphan receptor 1 (NOR-1), has been investigated for reliable diagnosis of ACC. The purpose of this study was to evaluate and compare the performance of NOR-1 antibody with DOG-1.

Materials and Methods

An IRB-approved retrospective search of the University of Florida Oral Pathology biopsy service database between 2000 and 2022 was performed for ACC cases. DOG-1, mammaglobin, and NR4A3 immunohistochemical staining was performed on all included cases with appropriate control using the commercially available antibody NOR-1 (sc-393902 [H-7], Santa Cruz Biotechnology Inc.).

Results

Eight cases of low-grade ACC were included. Patient age ranged between 40 and 95 years with equal gender distribution. One case was from parotid gland while all other cases were from buccal and labial minor salivary glands. Five cases were conventional solid variant, two were microcystic, and one papillary-cystic variants. Six cases out of eight stained positive for NOR-1 with variable intensity, while DOG-1 stained five cases out of eight. All cases were negative for mammaglobin.

Conclusions

NOR-1 staining revealed more sensitivity than DOG-1 for diagnosis of ACC within our case series. However, evaluation of this marker in additional studies with larger number of cases is recommended.