We aimed to detect truncated
CCN3 protein variants in
formalin-fixed
paraffin-embedded samples of eight Wilms'
tumors using anti-K19M and novel domain-specific
antibodies, anti-NH2, anti-NH3, anti-NH4, and anti-NH5 raised against C-terminal (CT) domain and modules 1, 2, 3, and 4 of the
CCN3 protein, respectively. In Wilms'
tumors, all the domain
antibodies except anti-NH4 exhibited both nuclear and cytoplasmic staining in blastema as well as primitive tubules. NH4 was detected only in the cytoplasm of
tumor cells. Normal fetal kidneys revealed mainly cytoplasmic immunoreactivity for all
antibodies in tubules and glomeruli, except for K19 and NH5, which showed some nuclear staining. Our data suggest expression of a truncated nuclear CCN3 variant lacking the
thrombospondin type-1-like domain and cytoplasmic full-length
CCN3 protein in
Wilms' tumor cells. In addition, normal fetal kidneys express mainly full-length
protein mostly localized to cytoplasm. Truncated
CCN3 protein in
Wilms' tumor cells may provide evidence for its tumorigenic role in these
tumors. Uniform NH5 staining compared to variable expression of K19M indicates that using NH5 is a better approach for detecting the CT domain of
CCN3 protein in archival specimens. Thus, the domain-specific
antibodies represent valuable tools for detecting
CCN3 protein variants in normal and neoplastic kidneys.