Histopathological and Immunohistochemical Study of Neoplastic Cell Heterogeneity in Early and Advanced Ovine Pulmonary Adenocarcinoma

Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring lung neoplasia in sheep caused by jaagsiekte sheep retrovirus (JSRV). JSRV infects alveolar type II pneumocytes (ATII) and club cells (CC), and the expression of viral oncoproteins induces a lung adenocarcinoma. The gross pathology of OPA exhibits differences in the anatomical patterns known as classical and atypical forms. Thirty natural OPA tumors, divided equally into early OPA tumors (Group A, GA), atypical tumors (Group B, GB), and classical tumors (Group C, GC), were obtained from adult sheep (2-9 years old). Tumor heterogeneity was studied comparing the histopathology (growth patterns, local invasion, mitotic figures, myxoid nodules), together with immunohistochemistry (IHC) using markers of JSRV-ENV, epithelial cells (ATII cells, CC, ki67), progenitor-stem epithelial cells (K5, p63, CD44), and the anterior grade protein 2 (AGR2). Papillary pattern was predominant in all groups. Lepidic pattern was also relevant in GA, and acinar pattern was relevant in GB. Low proliferation indexes and local invasion were observed in all groups. Myxoid nodules were few. IHC showed that all samples were positive for JSRV-ENV. Cell markers demonstrated that GA was different when compared to GB and GC, showing significantly the highest levels of CC, K5, and p63 positive tumor cells. There were no significant differences between GB and GC. The heterogeneity analysis of OPA tumors revealed that in early tumors, repair is important but is not reflected in classical or atypical different anatomical OPA forms.