DNA aneuploidy and cell proliferation in breast tumors

The cellular DNA content of 30 benign and 180 malignant breast tumors was analyzed by means of flow cytometry (FCM). All benign tumors exhibited a normal DNA content (diploid), whereas 65% of the malignant tumors showed an abnormal DNA content (aneuploid). The ploidy distribution of malignant tumors was bimodal with an increasing frequency near diploid DNA index (DI), and a second group had a DI ranging from triploid to tetraploid. In estimating the degree of malignancy eight independent histomorphologic and cytologic criteria were introduced. A good correlation was observed between DNA content abnormalities and the grade of differentiation of breast carcinomas. The percentage of S-phase cells of DNA aneuploid cell lines was significantly higher than in the diploid ones. The highly differentiated breast carcinomas (Grade 1) indicated lower S-phase values as compared to the undifferentiated (Grade 3) ones. S-phase values estimated by FCM were about two times higher than the 3H-thymidine labeling index (LI) obtained by an in vitro procedure. The data estimated in this study showed that DNA determinations as an adjunct to conventional histopathologic assessment may provide objective clinically relevant information with respect to the degree of malignancy and prognosis of patients with breast carcinoma.     

Cytochemical localization of peroxidase activity in normal, proliferating and neoplastic thyroid tissues of rats. An ultrastructural study.

In the control animals of thyroid peroxidase is localized within the membrane of rough endoplasmic reticulum, perinuclear cisternae, microvilli, lamellar structures of the GOLGI apparatus and dispersed through the cytoplasm small vesicles. 3 weeks treatment of the animals with MTU leads to disappearance of the peroxidase activity from the follicular cells. However, a prolongation of MTU administration until the 6th month and latter causes a reappearance of the peroxidase activity within the same structures of the proliferating cells as in the control animals. In the epithelial cells of follicular and papillary carcinomas the reaction product is observed predominantly within the membrane of the rough endoplasmic reticulum, perinuclear space and outher membrane of the microvilli. The changes in the inhibitory effect of MTU on the peroxidase activity during thyroid carcinogenesis are discussed.     

Interleukin‐1 expression in inflammatory myopathies: evidence of marked immunoreactivity in sarcoid granulomas and muscle fibres showing ischaemic and regenerative changes

The most frequent autoimmune adult inflammatory myopathies are dermatomyositis, polymyositis, inclusion body myositis, and sarcoid myopathy. Interleukin‐1 (IL‐1) is a pleiotropic molecule, implicated in the inflammatory process, but also in tissue protection and remodelling. We evaluated the immunocytochemical expression of IL‐1α and β in frozen muscle biopsy specimens from patients with dermatomyositis (15 cases), polymyositis (five cases), inclusion body myositis (five cases) and sarcoid myopathy (five cases). Positive immunoreactivities, were observed in both inflammatory cells and muscle fibres. Specificity of the immunostaining was assessed by Western blot experiments. IL‐1 positive inflammatory cells were rare in polymyositis and inclusion body myositis, moderately abundant in dermatomyositis, and prominent in sarcoid myopathy granulomas. In sarcoid myopathy, 24.6±4.1% inflammatory cells were IL‐1α‐positive and 45.2±2.6% were IL‐1β‐positive. IL‐1 positive muscle fibres were mainly observed in dermatomyositis, usually remote from inflammatory infiltrates. Positive immunostaining for IL‐1 was observed in fibres showing ischaemic punched‐out vacuoles, that correspond to areas of myosinolysis, in atrophic perifascicular fibres, and in fibres located within healing microinfarcts. All NCAM‐positive regenerating fibres were IL‐1 positive. We conclude that: (i) IL‐1 is expressed in granulomas of sarcoid myopathy, which is in keeping with the role ascribed to IL‐1 in the formation of granulomas; (ii) IL‐1 is expressed by muscle fibres undergoing ischaemic damage; and (iii) IL‐1 expression by muscle fibres is associated with myofibrillar protein breakdown and regeneration.