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Molecular and immunohistochemical analyses of the focal form of congenital hyperinsulinism. Mod Pathol 2006 Jan;19(1):122-9



Pubmed ID




Scopus ID

2-s2.0-32844459139   56 Citations


Congenital hyperinsulinism is a rare pancreatic endocrine cell disorder that has been categorized histologically into diffuse and focal forms. In focal hyperinsulinism, the pancreas contains a focus of endocrine cell adenomatous hyperplasia, and the patients have been reported to possess paternally inherited mutations of the ABCC8 and KCNJ11 genes, which encode subunits of an ATP-sensitive potassium channel (K(ATP)). In addition, the hyperplastic endocrine cells show loss of maternal 11p15, where imprinted genes such as p57(kip2) reside. In order to evaluate whether all cases of focal hyperinsulinism are caused by this mechanism, 56 pancreatectomy specimens with focal hyperinsulinism were tested for the loss of maternal allele by two methods: immunohistochemistry for p57(kip2) (n=56) and microsatellite marker analysis (n=27). Additionally, 49 patients were analyzed for K(ATP) mutations. Out of 56 focal lesions, 48 demonstrated clear loss of p57(kip2) expression by immunohistochemistry. The other eight lesions similarly showed no nuclear labeling, but the available tissue was not ideal for definitive interpretation. Five of these eight patients had paternal K(ATP) mutations, of which four demonstrated loss of maternal 11p15 within the lesion by microsatellite marker analysis. All of the other three without a paternal K(ATP) mutation showed loss of maternal 11p15. K(ATP) mutation analysis identified 32/49 cases with paternal mutations. There were seven patients with nonmaternal mutations whose paternal DNA material was not available, and one patient with a mutation that was not present in either parent's DNA. These eight patients showed either loss of p57(kip2) expression or loss of maternal 11p15 region by microsatellite marker analysis, as did the remaining nine patients with no identifiable K(ATP) coding region mutations. The combined results from the immunohistochemical and molecular methods indicate that maternal 11p15 loss together with paternal K(ATP) mutation is the predominant causative mechanism of focal hyperinsulinism.

Author List

Suchi M, MacMullen CM, Thornton PS, Adzick NS, Ganguly A, Ruchelli ED, Stanley CA


Mariko Suchi MD, PhD Associate Professor in the Pathology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

ATP-Binding Cassette Transporters
Adenosine Triphosphate
Chromosomes, Human, Pair 11
Congenital Hyperinsulinism
Cyclin-Dependent Kinase Inhibitor p57
Infant, Newborn
Microsatellite Repeats
Potassium Channels
Potassium Channels, Inwardly Rectifying
Receptors, Drug
Sulfonylurea Receptors
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a