Abstract Invasive lobular breast carcinoma (ILC) accounts for 10-15% of breast cancers diagnosed annually. Evidence suggests that some aspects of endocrine treatment response might differ between invasive ductal carcinoma (IDC) and ILC, and that patients with ILC have worse long-term survival. We analyzed The Cancer Genome Atlas dataset and observed lower levels of ESR1 mRNA (P=0.002) and ERα protein (P=0.038) in ER+ ILC (n=137) compared to IDC (n=554) and further confirmed the mRNA difference in a local UPMC cohort (ILC, n=143; IDC, n=877; P<0.005). In both datasets, the correlation between ESR1 mRNA and ERα protein was weaker in ILC suggesting differential post-transcriptional regulation of ERα. In vitro, 17β-estradiol (E2) decreased the rate of degradation and increased the half-life of ERα in ILC cell lines, whereas the opposite was observed in IDC cell lines. Further, E2 failed to induce robust ubiquitination of ERα in ILC cells. To determine the potential clinical relevance of these findings, we evaluated the effect of two selective estrogen receptor down-regulators (SERDs), ICI182,780 and AZD9496, on ERα turnover and cell growth. While ICI182,780 and AZD9496 showed similar effects in IDC cells, in ILC cell lines, AZD9496 was not as effective as ICI182,780 in decreasing ERα stability and E2 induced proliferation. Furthermore, AZD9496 exhibited partial agonist activity in growth assays in ILC cell lines. Our study provides evidence for a distinct ERα regulation by SERDs in ILC cell lines and therefore it is important to include ILC models into preclinical and clinical testing of novel SERDs.

CD is a rare autosomal recessive disease, characterized by multifocal cystic dilatation of intrahepatic bile ducts. The course of the disease is characterized by intrahepatic cholelithiasis, recurrent episodes of cholangitis, because of cholelithiasis, hepatic abscesses often ending in death caused by uncontrolled infection. Other conditions such as choledochal cyst and renal cystic disease are frequently associated, and patients have a higher risk for the development of cholangiocarcinoma. Endoscopic drainage of the bile duct is palliative and ineffective. OLT appears to be the treatment of choice. In monolobar cases partial liver resection has been shown to be a curative therapeutic option. We report on the course of disease in a Turkish girl who was diagnosed with CD in the neonatal period. At the age of 8.2 yr, she received OLT and is in good health 57 months post-transplantation.

Primary pancreatic lymphoma (PPL) is a rare form of extranodal lymphoma. So far, only in adults has a coincidence with diabetes mellitus (DM) been described. We report a nearly 9-year-old German boy presenting with a Burkitt lymphoma associated with a temporary insulin-dependent DM and exocrine insufficiency of the pancreas. After the patient went into remission, a spontaneous recovery of the endocrine pancreatic function was observed. On immunophenotyping, the lymphoma cells revealed expression of FasL suggesting a potentially apoptotic effect on pancreatic tissue. Beta cell impairment may have been caused by FasL resembling autoimmune diabetes.