# Proliferation-Based WHO Grading and Heterogeneous Gastrin Expression in Canine Gallbladder Neuroendocrine Tumors

## TL;DR

This study applies human WHO grading to canine gallbladder neuroendocrine tumors and finds they are mostly low-grade and rarely express gastrin.

## Contribution

The study introduces WHO-based grading for canine gallbladder neuroendocrine tumors and evaluates gastrin expression as a potential therapeutic target.

## Key findings

- All canine gallbladder neuroendocrine tumors were classified as low-grade (NETs) using WHO criteria.
- Only one out of 19 tumors expressed gastrin, indicating limited therapeutic relevance of this marker in dogs.

## Abstract

Efforts by the World Health Organization (WHO) have clarified the descriptive nomenclature and histologic grading of neuroendocrine neoplasms (NENs) in human medicine. Employing a standardized stratification scheme enhances prognostic accuracy and guides treatment recommendations. Yet, this classification system has yet to be applied consistently in veterinary pathology. The objective of this study was to apply the markers of cell proliferation used in the WHO grading system to canine gallbladder (GB) NENs. In this group, all canine GB NENs were classified as low-grade neuroendocrine tumors (NETs), which is prognostically favorable in human patients. The secondary aim of the project was to determine whether canine GB NENs expressed gastrin, a potential therapeutic target. Gastrin expression was measured using immunohistochemistry; only 1 out of 19 GB NETs was positive. The use of proliferative indices in the histologic characterization of canine GB NENs is likely to improve prognostic information. The expression of gastrin was limited in this group of canine GB NENs; assessment may be warranted in individual canine NEN patients experiencing emesis or hematemesis.

Efforts by the World Health Organization (WHO) have clarified the descriptive nomenclature and histologic grading of neuroendocrine neoplasms (NENs) in human medicine. Employing a standardized stratification scheme in conjunction with specific immunohistochemical markers, such as gastrin, enhances prognostic accuracy and guides treatment recommendations. Yet, this classification system has yet to be applied consistently in veterinary pathology. Histopathologic features and gastrin expression were analyzed in a group of canine gallbladder (GB) NENs. Based on the human WHO histologic system, which stratifies grade based on proliferative indices (mitotic count and Ki67%), all gradable GB NENs were classified as neuroendocrine tumors (NETs) rather than neuroendocrine carcinomas (NECs). Only one GB NET was positive for gastrin using immunohistochemical staining. Collectively, our data suggest that canine GB NENs have a lower grade than most human GB NENs and rarely express gastrin. The use of proliferative indices in the histologic characterization of canine GB NENs is likely to improve prognostic information. Given the limited expression of gastrin in these neoplasms in dogs, this marker is unlikely to be widely applicable as a druggable target.