Metastatic potential of ovine pulmonary adenocarcinoma: a comprehensive assessment of the draining pulmonary lymph nodes

Abstract

Ovine pulmonary adenocarcinoma (OPA), caused by Jaagsiekte sheep retrovirus (JSRV; family Retroviridae, taxon species Betaretrovirus ovijaa), is a viral oncogenic lung disease in sheep. Its metastatic potential remains under-evaluated. We investigated macrometastases (MACs), micrometastases (MICs), and isolated tumor cells (ITCs) in regional draining lymph nodes (DLNs) using histopathology and immunohistochemistry (IHC). Samples from 41 lung tumors and their regional DLNs were obtained from slaughtered Țurcană sheep. Histologically, all cases were diagnosed as OPAs. The classical or mixed OPA was observed in 37 of 41 (90%) cases; the remaining tumors were the atypical form. In 10 cases, myxoid growths were also detected. For IHC, anti-multicytokeratin, thyroid transcription factor 1, and JSRV antibodies were used to detect metastatic cells within DLNs. Neoplastic cells were identified in 16 of 41 (39%) DLNs, including 2 MAC, 7 MIC, and 7 ITC cases. Lung tumors >7 cm were significantly associated with lymph node metastasis (p < 0.05). A random forest model incorporating tumor volume, necrosis, mitotic count, and Ki67 index achieved the best performance (AUC = 0.70; accuracy = 62.5%; F1 = 0.57) for metastasis prediction. A benign epithelial inclusion was found within a DLN in one case, which has not been reported previously, to our knowledge. We found that OPA has a higher metastatic potential than previously recognized, particularly in larger tumors. Multivariate analysis, including additional tumor markers, likely would improve metastasis prediction. Our findings advance our understanding of OPA progression and its relevance as a comparative model for human lung adenocarcinoma.