Purpose Tumor inflammatory response was evaluated as a prognostic feature in triple-negative breast cancer (TNBC) and compared with the clinical prognosticators of breast cancer and selected biomarkers of cancer cell proliferation. Methods TNBC patients (n = 179) with complete clinical data and up to 18-year follow-up were obtained from Auria biobank,

SUMMARY Two sisters who died at the ages of 2* 5 years and 5 weeks are described. Both showed signs of panhypopituitarism. At necropsy, no hypophysis could be found in the first child and a rudimentary and partly ectopic hypophysis was found in the other. Both children had a flat, poorly developed sella turcica, and the sellar anomaly could be seen in skull x-rays. These patients represent a hereditary syndrome characterised by neonatal panhypopituitarism, hypoplasia of the pituitary gland, and flat sella turcica.Congenital hypopituitarism may result from various anomalies of the hypophysis-such as absence, hypoplasia, or ectopia of the hypophysis. It also occurs in anencephaly and holoprosencephaly and may be connected with anomalies in the proximity of the hypophysis (e.g. cleft lip and palate with pituitary insufficiency, septo-optic dysplasia, and pituitary dwarfism) (Rimoin and Schimke, 1971). Patients with aplasia, hypoplasia, or ectopia of the hypophysis show signs of hypopituitarism soon after delivery, with persistent hypoglycaemia as the most conspicuous clinical feature. Hypoglycaemia usually leads to convulsions and brain damage (Steiner and Lawrence, 1953;Ehrlich, 1957;Aimone and Campagnoli, 1970;Moncrieff et al., 1972;Johnson et al., 1973). The sella turcica was normal in many of the cases with hypophyseal aplasia or hypoplasia (Steiner and Boggs, 1965) but there were reports of a small sella in some of these cases (Blizzard and Alberts, 1956;Dunn, 1966;Ferrier and Stone, 1969).We report 2 sisters who died at ages 2 5 years and 5 weeks, both ofwhom showed clinical symptoms suggestive of panhypopituitarism. At necropsy the hypophysis was hypoplastic or absent and the sella turcica poorly developed and flat; sellar abnormality could be demonstrated radiologically. Findings suggest that hypoplasia of the hypophysis with a flat, poorly developed sella is an inherited clinical syndrome with characteristic radiological features. Case reports The parents, both healthy, lived in an area known to contain genetic isolates but there was no known consanguinity. The mother suffered from hydramnios during both pregnancies and had had slight toxaemia and abnormal glucose tolerance tests during her second pregnancy. Case 1. This baby girl born by caesarean section weighing 3990 g died at age 2 -5 years. She had only one umbilical artery. Her eyes were small and deeply set and the frontal bone was prominent, but otherwise the appearance was normal. She was jaundiced for 2 weeks after delivery. Soon after birth she developed severe hypoglycaemia which was treated with parenteral glucose infusions and cortisone. Hydrocortisone twice a week maintained normal blood glucose levels for a few months. This treatment was stopped at the age of one year and hypoglycaemic attacks reappeared 6 months later. She later developed epilepsy, probably secondary to brain damage caused by hypoglycaemia. Growth in weight and height was retarded. She suffered numerous infections-pneumonia and urinary tract infections several times and vi...

Purpose Triple-negative breast cancer (TNBC) is an aggressive disease lacking specific biomarkers to guide treatment decisions. We evaluated the combined prognostic impact of clinical features and novel biomarkers of cell cycle-progression in age-dependent subgroups of TNBC patients. Methods One hundred forty seven TNBC patients with complete clinical data and up to 18 year follow-up were collected from Turku University Hospital, Finland. Eight biomarkers for cell division were immunohistochemically detected to evaluate their clinical applicability in relation to patient and tumor characteristics. Results Age at diagnosis was the decisive factor predicting disease-specific mortality in TNBC (p = 0.002). The established prognostic features, nodal status and Ki-67, predicted survival only when combined with age. The outcome and prognostic features differed significantly between age groups, middle-aged patients showing the most favorable outcome. Among young patients, only lack of basal differentiation predicted disease outcome, indicating 4.5-fold mortality risk (p = 0.03). Among patients aged > 57, the established prognostic features predicted disease outcome with up to 3.0-fold mortality risk for tumor size ≥ 2 cm (p = 0.001). Concerning cell proliferation, Ki-67 alone was a significant prognosticator among patients aged > 57 years (p = 0.009). Among the studied cell cycle-specific biomarkers, only geminin predicted disease outcome, indicating up to 6.2-fold increased risk of mortality for tumor size < 2 cm (p = 0.03). Conclusion Traditional clinical features do not provide optimal prognostic characterization for all TNBC patients. Young age should be considered as an additional adverse prognostic feature in therapeutic considerations. Increased proliferation, as evaluated using Ki-67 or geminin immunohistochemistry, showed potential in detecting survival differences in subgroups of TNBC.

The present paper reports for the first time on the prognostic value of miRNA-494 in invasive breast cancer. Particularly, detection of miRNA-494 could benefit patients with node-negative breast cancer in identifying subgroups with aggressive disease. Based on our experience, the developed automatic ISH method to visualize altered levels of miRNAs-494, -205, -21 and -126 could be applied to routine pathology diagnostics providing that conditions of tissue treatment, especially fixation delays, are managed.