Familial adenomatous polyposis associated with multiple endocrine neoplasia type 1-related tumors and thyroid carcinoma: A case report with clinicopathologic and molecular analyses
ABSTRACT We describe a sporadic case with familial adenomatous polyposis, multiple endocrine neoplasia type 1 (MEN1)-related tumors (an endocrine cell tumor of the pancreas and bilateral parathyroid tumors), and a papillary thyroid carcinoma. To clarify how mutations of the adenomatous polyposis coli ( APC ) gene and the MEN1 gene, responsible for familial adenomatous polyposis and MEN1, respectively, might have contributed to tumorigenesis in this case, we studied germline mutations in both genes and loss of heterozygosity at their genetic loci in multiple lesions. In addition, we performed immunohistochemistry for beta-catenin, associated with the function of the APC gene. A germline mutation was found in the APC gene but not in the MEN1 gene. Normal allelic loss at the APC gene locus was observed in bilateral parathyroid tumors. Immunohistochemical staining of beta-catenin demonstrated accumulation in the cytoplasm in addition to membrane staining in all analyzed tumors and a strong nuclear reaction in the endocrine cell tumor of the pancreas. The presence of normal allelic deletions of the APC gene in bilateral parathyroid tumors and nuclear staining of beta-catenin in the pancreatic tumor in addition to the germline mutations suggests that functional loss of the APC gene played an important role not only in familial adenomatous polyposis but also in the MEN1-related tumors in this case.
- American Journal of Surgical Pathology 04/2003; 27(3):412-3. DOI:10.1097/00000478-200303000-00018 · 4.59 Impact Factor
Article: Papillary thyroid carcinomaAmerican Journal of Surgical Pathology 09/2003; 27(8):1176-7. DOI:10.1097/00000478-200308000-00022 · 4.59 Impact Factor
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ABSTRACT: The effects of prolactin (PRL) on transcript profile expression in 24h cultured pancreatic adult rat islets were investigated by cDNA expression array analysis to identify possible candidate mRNA species that encode proteins involved in the maturation and growth of the endocrine pancreas. The expression of 54 out of 588 genes was altered by treatment with PRL. The differentially expressed transcripts identified were distributed in six main categories involved in cell proliferation and differentiation, namely, cell cycle regulation, signal transduction, transcription factors and coactivators, translational machinery, Ca(2+)-mediated exocytosis, and immuno-response. Treatment with PRL also reduced the expression of genes related to apoptosis. Several genes, whose expression was previously not known to be modulated by PRL were also identified including macrophage migration inhibitory factor and Ca(2+)/calmodulin-dependent protein kinase IV. These genes have recently been shown to play a crucial role in insulin secretion and insulin gene expression, respectively. Treatment with PRL also modified the expression of AKT2 and bone morphogenetic protein receptor 1A that control glucose homeostasis and directly affect the behavior of endocrine pancreas and/or the sensitivity of target tissues to insulin. In conclusion, PRL induces several patterns of gene expression in pancreatic islet cells. The analysis of these different patterns will be useful for understanding the complex mechanism of action of PRL in the maturation and differentiation of pancreatic islets.Molecular and Cellular Endocrinology 06/2004; 220(1-2):41-50. DOI:10.1016/j.mce.2004.04.001 · 4.24 Impact Factor