Immunohistochemical Evaluation of RUNX2, Osteocalcin, and Vimentin in Feline Primary Pulmonary Carcinomas

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.