Ugo Di Tondo

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.

DNA/protein flow cytometry as a predictive marker of malignancy in dysplasia-free Barrett's esophagus: Thirteen-year follow-up study on a cohort of patients

Intestinal metaplasia identifies Barretts esophagus (BE) and is associated with an increased risk for esophageal adenocarcinoma. Dysplasia occurs as an intermediate step. However, progression from metaplasia to neoplasia without the demonstration of dysplasia has been described. The role of dual-parameter flow cytometry (FC) as a predictor of neoplastic risk in dysplasia-free cases was evaluated. DNA/protein FC and histology were performed on 362 samples from 30 dysplasia-free BE patients, followed up since 1985 once every 1-2 years. Nine cases were aneuploid, five of which (group IV) were frankly aneuploid; in the other four cases (group III), aneuploidy was detectable by dual-parameter analysis only. Twenty-one patients were diploid. Twelve (group II) also had an abnormally high G1-phase protein content compared to group I (nine patients), which were diploid with a low-moderate protein content. In three patients of group IV an adenocarcinoma in situ was diagnosed, after 5, 6, and 10 years, respectively. In two patients of group III, a low- and a high-grade dysplasia were observed at 3 and 6 years follow-up, respectively. One patient of group I first acquired a high protein content, then an aneuploid DNA content, and then progressed to adenocarcinoma (12 years). None of the still diploid patients (17 cases) have progressed to dysplasia or cancer compared with 6 of 13 presently aneuploid patients (P < 0.01). In conclusion, DNA/protein FC is a marker of increased malignant potential and thus may be used to detect patients at higher risk in dysplasia-free BE and assist in understanding the various stages of malignant transformation in long-term follow-up studies.

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.

Osteo-odonto-keratoprosthesis: Description of Surgical Technique with Results in 85 Patients

Osteo-odonto-keratoprosthesis is a technique designed for patients with severe corneal opacification who would be at high risk of graft rejection should donor tissue transplantation be performed. Because of the isolation of the prosthetic implant from the tissues that the technique provides, the authors are of the opinion that it is the only viable option in such patients. The visual outcome and complications of the procedure in a series of 85 cases are presented.

Inflammatory Pseudotumour of the Liver — Evidence for Malignant Transformation

A case of inflammatory pseudotumour of the liver is reported, and evidence is presented for its subsequent evolution into malignant non-Hodgkins lymphoma. Such postulated malignant transformation challenges the assumption that hepatic inflammatory tumours are entirely benign lesions.

Primary Non-Hodgkin's Lymphoma of the Liver

The clinicopathological features of a rare case of primary non-Hodgkins hepatic lymphoma (PHL) are described and compared to those of the other 76 cases reported in the world literature. PHL is mainly a disease of Caucasian, middle-aged males and, in approximately half of the reported cases, was associated with other diseases involving depression or chronic stimulation of the immune system. Right upper abdominal and epigastric pain with loss of weight are the most common presenting symptoms. The tumour is usually a single large mass involving both hepatic lobes and is almost invariably composed of lymphocytes reacting with B-cell markers. Most tumours are of intermediate or high grade according to the classification of the Working Formulation for Clinical Usage. No correlation is apparent between gross appearance of PHL (massive or nodular) and grade of severity. Chemotherapy or radiotherapy alone appears to be ineffective, while relatively good results can be obtained with combination modalities.

Differential Expression of IGF-I and IGF-II in Eutopic and Ectopic Endometria of Women With Endometriosis and in Women Without Endometriosis

PROBLEM: Factors regulating the development, growth, and differentiation of endometrial cells of endometriotic lesions are poorly understood. To investigate the paracrine‐autocrine regulation of ectopic endometrial cell growth, the expression of IGF‐I and IGF‐II were studied.

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.

Immunohistochemical localization of the growth hormone in human endometrium and decidua.

Problem:  Recent evidence of growth hormone (GH) receptor expression in rat endometrium and human myometrium have focused our attention on the role of the GH in endometrial development. We tested the expression of GH in the human endometrium throughout the menstrual cycle and during pregnancy.

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.