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Figure 6.

Figure 6

Clonal orthotopic PB-Cre4+; Ptenfl/fl;TP53fl/fl carcinomas demonstrate multilineage differentiation, metastasis, and epithelial to mesenchymal transition. Sequential serial sections of a representative Clone 1 orthotopic prostate carcinoma (left column), a Clone 1 lung metastasis originating from this same primary carcinoma (middle column), and a Clone 2 sarcomatoid carcinoma (right column), staining with H&E (A–C) or IHC (D–R) for cytokeratin 8 (CK8), cytokeratin 5 (CK5), TP63, synaptophysin (SYN), and androgen receptor (AR). A: Clone 1 gives rise to adenosquamous carcinomas (A) with heterogeneous luminal cytokeratin 8 (CK8) expression (D) and basal cytokeratin 5 (CK5) expression (G). J: Definitive basal cells express nuclear TP63 (arrows in J). M: Heterogeneous synaptophysin (SYN) expression is observed in both adenocarcinoma and squamous portions of Clone 1 orthotopic tumors. P: Androgen receptor expression is heterogeneous ranging from strong nuclear expression (arrow) to weak nuclear and cytoplasmic expression (arrowhead). B: Clone 1 orthotopic tumors commonly metastasize to the lungs where metastases display either a luminal phenotype or are biphenotypic. Luminal phenotype lung metastasis that coexpresses CK8 (E) and CK5 (H) but not TP63 (K). N: Synaptophysin expression is common in Clone 1 lung metastases. Q: Androgen receptor expression in lung metastasis is generally low in the nucleus, yet high in the cytoplasm. C: Clone 2 orthotopic carcinomas undergo EMT to form sarcomatoid carcinomas with only occasional glandular differentiation. Sarcomatoid carcinomas lose cytokeratin expression leaving only occasional foci with weak CK8 expression (arrows in F). No CK5 (I) or TP63 (L) expression is observed. O: Weak cytoplasmic synaptophysin expression is common in clone 2 tumors. R: Androgen receptor expression is heterogeneous and generally lower in Clone 2, with most tumor cells having weak or absent nuclear expression, and low cytoplasmic expression. All images taken at similar resolution (×400). Scale bar = 100 μm.