Frequent nuclear beta-catenin accumulation and associated mutations in endometrioid-type endometrial and ovarian carcinomas with squamous differentiation

Focal squamous differentiation is a common feature of endometrioid endometr ial and ovarian carcinomas (E-Em and E-Ova Gas). A close association betwee n mutated beta -catenin accumulation and alteration in cellular morphology has recently been demonstrated in murine L cell lines. To clarify the possi ble role of beta -catenin abnormalities and changes in tumour morphology, 6 0 grade (G) 1 or G2 E-Em Cas with areas of squamous differentiation (SqD), including morules and squamous metaplastic (SqM) foci, as well as 32 G1 or G2 tumours without such lesions, were investigated and the results compared with findings for c-jun and wnt-1 expression. Twenty-three E-Ova Gas, with and without SqD lesions, were also examined. In E-Em Gas, frequent nuclear beta -catenin accumulation was observed in 22 (84.6%) of 26 tumours with m orules and 15 (45.5%) of 33 with SqM foci, in contrast to 4 (12.5%) of 32 w ithout such lesions. Similar findings were also noted for mutations in exon 3 of the beta -catenin gene, involving codons 32, 33, 34, 37, 41, and 45, the single nucleotide substitutions being identical between Son and the sur rounding carcinoma tissue in most informative cases. The mutations were pos itively related to nuclear immunopositivity, but inversely to membrane expr ession, while there was no association with the status of c-jun or wnt-1. T hese E-Ova Gas, nuclear beta -catenin accumulation and mutations a ere limi ted to tumours with SqD features, independent of c-jun and wnt-1 status. Th ese data indicate that beta -catenin abnormalities are relatively common in E-Em and E-Ova Cas with SqD features, implying a role in the squamous diff erentiation of tumour cells, not necessarily related to c-jun and/or wnt-1 status. Copyright (C) 2001 John Wiley & Sons, Ltd.