Absence of Canonical WNT Signaling in Adult Renal Cell Tumors of Embryonal Origin.

BACKGROUND/AIM: The canonical β-catenin pathway is involved in the development of Wilms' tumor, but its role in adult renal cell tumors (RCT) of embryonal origin is not yet known.

MATERIALS AND METHODS: We sequenced the catenin beta 1 (CTNNB1) gene in papillary RCTs, applied the TOPflash/FOPflash reporter plasmid system on cell lines, and examined the β-catenin protein expression by immunohistochemistry.

RESULTS: The absence of mutations in CTNNB1 and low TOPflash/FOPflash ratio in tumor cell lines indicated the absence of active Wingless-type MMTV integration site family (WNT) signaling in RCTs. The weakly cytoplasmic tending towards membranous expression of β-catenin in RCT is analogous to cellular differentiation in the embryonal kidney rather than tumorigenic activation of WNT signaling.

CONCLUSION: The localization of β-catenin in papillary RCT, metanephric adenoma and mucinous tubular and spindle-cell carcinoma corresponds to that of emerging tubules of kidney at distinct stage of maturation, indicating their embryonal origin.