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Immunohistochemical Evaluation of RUNX2, Osteocalcin, and Vimentin in Feline Primary Pulmonary Carcinomas
by
, , , , , and
Alexandra Morar
1, 
Corina Toma
1,*,
Dragoș Hodor
1,
Mara-Georgiana Haralambie
1,
Iulia Pană
1,
Alexia-Teodora Hoța
1,
Diana Bochynska
2,
Claudiu Gal
1,3 and
Cornel Cătoi
1 1
Department of Veterinary Pathology, Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, 400372 Cluj-Napoca, Romania
2
Department of Veterinary Pathology, Ross University School of Veterinary Medicine, 00265 Basseterre, Saint Kitts and Nevis
3
Department of Veterinary Pathology, Synevovet, Industriilor 25, 077040 Chiajna, Romania
*
Author to whom correspondence should be addressed.
Vet. Sci. 2026, 13(9), 980; https://doi.org/10.3390/vetsci13090980 (registering DOI)
Submission received: 12 August 2026
/
Revised: 5 September 2026
/
Accepted: 16 September 2026
/
Published: 17 September 2026
(This article belongs to the Special Issue Focus on Tumours in Pet Animals: 3rd Edition)
Simple Summary
Primary lung cancer in cats is rare but often spreads directly to the digits, a condition known as feline lung-digit syndrome. The biological reasons for this unique bone-targeted spread remain poorly understood. In this study, we examined lung tumors from 18 cats, including 5 cases where the cancer had spread to the digits. We tested these samples for RUNX2, osteocalcin, and vimentin. We found that tumors spreading to the toes had significantly higher levels of RUNX2 protein compared to those that did not. Ultimately, this study provides the first descriptive data showing that higher RUNX2 immunoreactivity is observed in primary pulmonary carcinomas from cats with documented digital metastasis.
Abstract
Feline primary pulmonary carcinomas (PPCs) occasionally exhibit a distinctive metastatic tropism for the distal digits, clinically recognized as feline lung-digit syndrome or MODAL syndrome. The molecular mechanisms driving this unique behavior remain poorly understood. This retrospective study evaluated 18 feline PPCs to investigate the expression of bone-related markers (RUNX2, osteocalcin), vimentin, Ki-67, MCK, and TTF-1. Cases were classified into PPCs with (n = 5) and without (n = 13) documented digital metastases. Adenosquamous carcinoma was the predominant histological subtype (61.1%); all tumors expressed MCK and TTF-1. While osteocalcin and aberrant vimentin expression were detected across both groups, they did not differ significantly between groups. Conversely, RUNX2 nuclear immunoreactivity was significantly elevated in cases with digital metastasis (p = 0.006). Furthermore, the evaluation of matched primary and metastatic lesions demonstrated that digital metastases retained the histological and immunophenotypic profiles of their primary tumors. Overall, this first characterization demonstrates that higher RUNX2 immunoreactivity was observed in primary pulmonary carcinomas from cats with documented digital metastasis. However, without the evaluation of extra-digital metastases, it remains undetermined whether this reflects a specific tropism for the digits or a general metastatic competence.
