Endocrine Abstracts

Introduction: Focal congenital hyperinsulinism (F-CHI) is caused by dual-hit pathology, comprising a paternally-inherited ABCC8/KCNJ11 mutation and somatic loss of the maternal allele at chromosome 11p15. This leads to dysregulation of insulin secretion and β-cell overgrowth with a focal domain.

Objectives: To compare the proliferative index (PI) of the F-CHI lesion and non-lesion pancreatic tissues to age-matched control pancreata and insulinoma tissues.

Methods: Ki67 immunostaining was used to quantify the PI of paraffin-embedded F-CHI tissue (n=8; age 2–10 months at pancreatic surgery; positive for ABCC8 mutations), age-matched control pancreata (n=12) and insulinomas (n=3, age 5–16 years). The PI was derived from the total number of Ki67-positive cells expressed as a percentage of the total cell count using digitized images of histological sections of tissue, ~35 000 cells per tissue (n=30 tissue sections in total).

Results: Control tissue showed age-related decline in PI from >8% of total cells at 2 days to <0.5% at 10 months. In comparison, F-CHI tissue retained a high PI inside and outside the lesion. Within the lesion, PI was increased by an average (±SEM) 1.4-fold (4.7%±0.5) (n=5) vs controls in children <4 months of age at surgery, which became statistically significant at age >4 month, ninefold (4.2%±0.8) (n=3) P=0.025. Interestingly, the PI of non-islet and islet tissue outside the focal lesion was also increased; at >4 months this was increased to 7.3-fold (3.4%±0.4) in non-islet tissue (P=0.02, n=3) and 2.3-fold (1.2%±0.4) in islets (P=0.01). These trends were not seen in insulinoma tissue as PI values were ≤ 0.5% in both the lesion and non-lesion tissue.

Summary/conclusion: Enhanced proliferation is retained both inside and outside the F-CHI lesion with more gradual age related decline. The increased proliferation rate in F-CHI cannot be solely attributed to maternal 11p15 deletion as this is confined to the lesion.