Piero Luigi Alo

Fatty acid synthase (FAS) predictive strength in poorly differentiated early breast carcinomas.

Aims and background Many normal and human cancer tissues express fatty acid synthase (FAS), the major enzyme required for endogenous fatty acid biosynthesis. Strong expression of FAS seems to be associated with a poor prognosis. This study examines the strength of FAS and other common markers of relapse in poorly differentiated breast carcinoma. Materials and methods Fifty-one patients with poorly differentiated ductal infiltrating breast carcinomas were followed up for more than 10 years. Immunohistochemical detection of FAS was associated with morphological features of the tumors, with immunohistochemical expression of c-erbB-2, cathepsin D, estrogen and progesterone receptor status and with DNA ploidy in order to detect a statistical correlation. Results The chi-square test revealed a correlation between FAS and peritumoral lymphatic vessel invasion (PLVI) (P = 0.001). Univariate analysis showed that FAS was correlated with disease-free survival (DFS) (P = 0.0001). Other prognosticators associated with DFS were PLVI (P = 0.002), estrogen (P = 0.008) and progesterone receptor status (P = 0.007). Bivariate analysis showed that FAS was a further prognostic discriminant of DFS within the ER, PgR and PLVI subsets. Discussion FAS is a reliable prognosticator of recurrence in poorly differentiated early breast carcinomas. Association of FAS with PLVI may be useful to plan a correct follow-up in patients with breast neoplasms.

Adrenomedullin, a New Vasoactive Peptide, Is Increased in Preeclampsia

Adrenomedullin is a novel peptide that elicits a long-lasting vasorelaxant activity. Recently, we found high concentrations of adrenomedullin in maternal and umbilical cord plasma and in amniotic fluid in full-term human pregnancy, indicating a role of this peptide during gestation. To investigate the possibility that adrenomedullin is involved in the pathophysiology of preeclampsia, we measured its concentration in maternal and fetoplacental compartments. We studied 12 normotensive nonpregnant women, 13 hypertensive nonpregnant subjects, 29 patients with preeclampsia, and 30 normotensive pregnant women. In all patients, plasma was collected from the cubital vein, and amniotic fluid samples were obtained by transabdominal amniocentesis or at elective cesarean section. Plasma samples from umbilical vein and placental tissues were collected at delivery. Adrenomedullin was assayed on plasma and amniotic fluid samples using a specific radioimmunoassay, and its localization and distribution on placental sections was determined by immunohistochemistry. Adrenomedullin concentrations were higher in hypertensive than in normotensive nonpregnant patients. Pregnant women had higher adrenomedullin levels than nonpregnant subjects, although maternal plasma adrenomedullin concentrations did not differ between normal pregnant and preeclamptic women. Preeclamptic patients showed higher concentrations (P<0.01) than normotensive pregnant women of adrenomedullin in amniotic fluid (252+/-29 versus 112+/-10 fmol/ micromol creatinine) and umbilical vein plasma (18.1+/-2.1 versus 8. 5+/-1.1 fmol/mL). Increased local production of adrenomedullin is associated with preeclampsia. The fetus seems to be responsible for the higher levels of this hormone. Increased adrenomedullin concentrations may be necessary to maintain placental vascular resistance and/or fetal circulation at a physiological level.

Immunohistochemical Expression of Human Erythrocyte Glucose Transporter and Fatty Acid Synthase in Infiltrating Breast Carcinomas and Adjacent Typical/Atypical Hyperplastic or Normal Breast Tissue

To evaluate the immunohistochemical expression of GLUT1, human erythrocyte glucose transporter 1, and fatty acid synthase (FAS), 66 human breast carcinomas and adjacent peritumoral tissue were studied. GLUT1 and FAS were expressed in 53 and 61 carcinomas, in 17 and 14 typical/atypical hyperplastic tissues, and in 16 and 13 tissues adjacent to tumor normal breast tissue, respectively. Statistical analysis revealed association between invasive carcinomas, invasive carcinomas with in situ component and GLUT1 immunostaining. GLUT1 staining was associated with tumor grade, FAS with tumor stage, and GLUT1 and FAS coexpression with tumor grade. Controls expressed no immunostaining. GLUT1 and FAS are new markers involved in the biologic activities of cancer cells. GLUT1 and FAS coexpression may indicate increased use of energy by the neoplastic cells correlated with poorly differentiated features and aggressive behavior. The innovative finding that GLUT1 and FAS are observed in mammary carcinoma adjacent nonneoplastic tissues may suggest a role in detecting initial phases of breast carcinogenesis.

Immunohistochemical study of fatty acid synthase, Ki67, proliferating cell nuclear antigen, and p53 expression in hyperplastic parathyroids

Patients with secondary hyperparathyroidism following chronic renal disease frequently develop hyperplastic parathyroids. Hyperplastic parathyroids have an increased number of chief cells, a decreased amount of stromal fat, and a nodular or diffuse histologic pattern. Hyperplastic parathyroids may also express higher proliferative activity compared with controls. We evaluated the morphologic features and immunohistochemical expression of fatty acid synthase (FAS), Ki67, proliferating cell nuclear antigen, and p53 protein in 78 hyperplastic parathyroids from 20 patients with secondary hyperparathyroidism. Twenty normal parathyroids incidentally removed during nonneoplastic thyroid surgery were used as controls. Our results showed that hyperplastic glands overexpress FAS (P =.06). Statistical analysis also revealed a significant association between FAS and p53 protein (P =.006) and between FAS and hyperplastic glands with a predominant nodular pattern (P =.02). Hyperplastic parathyroids from patients with chronic renal failure strongly express FAS. Fatty acid synthase may therefore be a potential biological indicator of highly proliferating parathyroid cells.

Changes in plasma adrenomedullin levels during the menstrual cycle.

We investigated whether the levels of adrenomedullin, a novel peptide produced by several tissues, including the pituitary gland, change during the ovarian cycle. We studied 13 healthy women with regular menstrual cycles. Plasma samples were collected at 7, 14, 21 and 28 days of the ovarian cycle and assayed for adrenomedullin 1-52 using a specific RIA. LH, FSH, 17beta-estradiol, and progesterone concentrations were also determined. The adrenomedullin profile during ovarian cycle was similar to that of LH; plasma adrenomedullin increased from 10.9 pg/ml at the 7th day to 15.1 pg/ml at the 14th, and decreased to 8.5 pg/ml in the subsequent menses. The changes in plasma adrenomedullin were related to changes in LH and 17beta-estradiol. The cause of the increase in adrenomedullin levels during the late follicular phase of the menstrual cycle is not clear. Since it has been demonstrated that adrenomedullin is involved in the regulation of hypothalamus-pituitary-adrenal gland and its secretion is regulated by sex hormones we speculate that adrenomedullin could also play a role in regulating the hypothalamus-pituitary-ovary feedback. Alternatively it may be involved in the regulation of fluid and electrolyte homeostasis during the menstrual cycle.

Immunohistochemical Localization of Adrenomedullin in Fetal and Neonatal Lung

Adrenomedullin is a potent hypotensive peptide that has been demonstrated to increase pulmonary blood flow in fetal sheep. To examine whether adrenomedullin plays a role in the transitional changes of human pulmonary blood flow at birth, we have evaluated, by immunohistochemistry, its presence and distribution in fetal lung during gestation using a polyclonal antibody directed toward human adrenomedullin 1-52. We collected lung specimen from abortive fetuses (n = 6), preterm neonates (n = 4), and term infants (n = 3). Two adult lung specimen were used as controls. Immunoreactive adrenomedullin was detected in fetal lung collected as early as at 18 wk of gestation and in all tissues throughout gestation. Adrenomedullin was localized predominantly in the epithelial cells of bronchi, with an apical distribution. Endothelial cells also stained for adrenomedullin. The intensity of staining and the percentage of positive bronchial epithelial cells increased as gestation progressed; but staining for adrenomedullin was absent in tissues collected after breathing and in the adult controls. These findings indicate that adrenomedullin may play an important role in respiratory homeostasis at birth. Moreover, the immunohistochemical expression of AM in the late organogenetic period and its increasing staining during fetal lung development may suggest a possible role in the mechanisms of fetal lung differentiation and/or maturation.

Fatty acid synthase expression in Paget's disease of the vulva

Summary:We explored the immunohistochemical expression of fatty acid synthase (FAS) in Pagets disease of the vulva (PDV) and its association with clinico-pathological features. FAS is a recently discovered molecule involved in energy supply of normal cells. FAS is also overexpressed in neoplastic tissues because of their increased necessity of energy. Specimens from 20 patients with PDV were immunohistochemically evaluated; increased FAS expression was observed in 7 of 8 patients with invasive PDV (87%), in 3 of 4 patients with microinvasive PDV (75%), and in 1 of 8 patients with noninvasive PDV (12%). Statistical analysis revealed that increased FAS expression was associated with invasive PDV (p = 0.04). To our knowledge, this association of FAS in PDV is the first to be reported in literature. These observations reveal that FAS is a reliable marker of aggressiveness in PDV. The knowledge of FAS statistical association in invasive PDV is an important finding that may stratify these patients in different prognostic groups and determine therapeutic approaches for patient care.

Unsuspected chronic ectopic pregnancy in a patient with chronic pelvic pain

‘Chronic ectopic pregnancy’ is a clinico-pathological entity that results from abortion or minor ruptures of a tubal pregnancy with a subsequent inflammatory response, extensive adhesions and mass formation, in which chorionic villi may be w x present 1]3 . The term chronic describes only the presence of a mass of gestational origin and does not imply chronicity of pregnancy. This condition is difficult to diagnose. Pelvic pain, hemodynamic stability, high incidence of negative pregnancy tests, due to the presence of non-viable trophoblast, and regular cycles are often present w x 1]3 . Sonographic patterns are poorly specific. A correct diagnosis is obtained only during or even after surgery. We report a case of a 30-year-old woman, complaining of acyclic pelvic pain, dysmenorrhea and deep dyspareunia, with regular menses and several negative pregnancy tests. Four

Laparoscopic diagnosis and treatment of a well-differentiated papillary mesothelioma of the peritoneum

Well-differentiated papillary mesothelioma is a rare neoplasm of peritoneum, found mainly in women of reproductive age, and usually misdiagnosed as an ovarian mass. A 46-year-old woman was clinically suspected of having an adnexal mass. Peritoneal mesothelioma was diagnosed and successfully removed at laparoscopy. Laparoscopy allows differentiation from ovarian serous tumors and treatment of the lesions. Long follow-up is recommended because of the tendency to recur.

Overexpression of Fatty Acid Synthase in Ulcerative Colitis

Fatty acid synthase is an enzyme that catalyzes the synthesis of long-chain fatty acids. The enzyme expression is minimal in adult tissues and very high in many cancers. Ulcerative colitis is a chronic inflammatory bowel disease that, when long-standing, is associated with an increased risk of colon cancer. The aim of the present study was to establish whether fatty acid synthase levels in the mucosa without dysplasia of patients with long-standing ulcerative colitis were higher than in control subjects. Three groups of patients were selected: 30 with active ulcerative colitis, 30 with ulcerative colitis in remission, and 30 undergoing colonoscopy for colorectal cancer screening, as healthy control subjects. Fatty acid synthase expression was evaluated with immunohistochemical procedures. The enzyme was detected in all patients with active colitis, in most patients with quiescent disease, in both pathologic and normal mucosa, but in only 3 healthy control subjects. Our results suggest that extension of ulcerative colitis is greater than that revealed by common diagnostic techniques.