Frequent mutation and nuclear localization of β-catenin in sertoli cell tumors of the testis.
The Sertoli cell tumor (SCT) of the testis is a sex cord stromal tumor, usually sporadic, rarely associated with genetic syndromes. Much remains unclear about the molecular genetic changes involved in SCT and its histogenesis. Recently, nuclear β-catenin immunostaining has been reported in a case of bilateral SCT, but the molecular basis of the aberrant nuclear β-catenin expression remains uncertain. In the present study, β-catenin immunohistochemical assay and mutational analysis of exon 3 of the CTNNB1 gene by direct sequencing were performed in 14 SCTs, 2 of which had an unfavorable clinical course. Immunohistochemical study showed that β-catenin was located in the cytoplasm of tumor cells in 4 cases (28.6%) and in both the nuclei and the cytoplasm in the remaining 10 cases (71.4%). β-Catenin mutations were detected in 10 of the 14 patients (71.4%) under evaluation. Ten of 10 mutation-carrying cases showed strong nuclear and diffuse cytoplasmic β-catenin immunoreactivity. Seven of the 8 CTNNB1-mutated tumors tested for cyclin D1 displayed diffuse immunoreactivity in the nuclei of tumor cells. We conclude that CTNNB1 exon 3 mutations are likely to be involved in the pathogenesis of male SCT with nuclear accumulation of β-catenin and affect the expression of cyclin D1.
Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Federica
F
Perrone
Alessia
A
Bertolotti
Gabriella
G
Montemurro
Biagio
B
Paolini
Marco A
MA
Pierotti
Maurizio
M
Colecchia
D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001706:Biopsy; D002467:Cell Nucleus / Q000737:chemistry*; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000032:analysis; D003593:Cytoplasm / Q000737:chemistry; D004252:DNA Mutational Analysis; D005091:Exons; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012707:Sertoli Cell Tumor / Q000737:chemistry* / Q000235:genetics* / Q000473:pathology; D013736:Testicular Neoplasms / Q000737:chemistry* / Q000235:genetics* / Q000473:pathology; D055815:Young Adult; D051176:beta Catenin / Q000032:analysis / Q000235:genetics
D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; C495270:CTNNB1 protein, human; D051176:beta Catenin; D019938:Cyclin D1