, Volume 12, Issue 2, pp 125-136

Analysis of β-catenin mutations and α-, β-, and γ-catenin expression in normal and neoplastic human pituitary tissues

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Abstract

The cadherin-catenin system mediates Ca2+-dependent cell-cell adhesion, and genetic alterations in these molecules play a significant role in multistage carcinogenesis. Mutations in the β-catenin gene, mostly affecting exon 3, have been detected in malignant cell lines and in primary tumors. Immunohistochemical abnormalities in α-, β-, and γ-catenin have been reported in malignant and benign tumors, and nuclear localization of β-catenin has been associated with mutations in exon 3 of this gene.

Mutational analysis of exon 3 of the β-catenin gene was undertaken by polymerase chain reaction (PCR) and sequencing using genomic DNA extracted from frozen tissues, including 4 normal pituitaries, 22 pituitary adenomas, and one pituitary carcinoma. Frozen sections from these cases were used for immunohistochemical detection of β-catenin. We also analyzed immunohistochemical expression of α-, β-, and γ-catenin by paraffin sections from 154 pituitary tumors, including 148 adenomas and 6 carcinomas. Genomic DNA was extracted from paraffin sections of 2 gonadotroph tumors showing nuclear staining for β-catenin and was used for PCR and sequencing of exon 3 of the β-catenin gene.

No mutations in exon 3 of the β-catenin gene were found in any of the 23 cases analyzed by PCR and sequencing. In addition, the 2 cases studied by paraffin section immunohistochemistry, with nuclear staining for β-catenin, were negative for mutations in this exon. Normal pituitary expressed all three catenin proteins. Immunostaining usually showed a membranous pattern of reactivity and was generally stronger in normal pituitary than in the adjacent adenomas. Stains for α-catenin were positive in fewer tumors than for β-catenin. The lowest frequency immunopositive tumors and the weakest immunostaining was for γ-catenin. All medically treated prolactinomas were negative for γ-catenin, whereas treated growth hormone adenomas were less often positive for both α- and γ-catenin than for untreated tumors. The percentage of positive cases for β-catenin was the same in these two groups. Most pituitary carcinomas were negative for both α- and γ-catenin but were β-catenin positive.

These results indicate that (i) mutations in exon 3 of the β-catenin gene are uncommon in pituitary tumors, and (ii) expression of α-, β-, and γ-catenin is decreased in pituitary adenomas compared to normal pituitary tissues.