The assessment of angiogenesis and fibroblastic stromagenesis in hyperplastic and pre-invasive breast lesions.

BACKGROUND: To investigate the changes of the neoplastic microenvironment during the different morphological alterations of hyperplastic and pre-invasive breast lesions. METHODS: 78 in situ ductal carcinomas of all degrees of differentiation, 22 atypical ductal hyperplasias, 25 in situ lobular carcinomas, 18 atypical lobular hyperplasias, 32 ductal epithelial hyperplasias of usual type and 8 flat atypias were immunohistochemically investigated for the expression of vascular endothelial growth factor (VEGF), smooth muscle actin (SMA) and CD34, while microvessel density (MVD) was counted using the anti-CD31 antibody. RESULTS: VEGF expression was strongly correlated with MVD in all hyperplastic and pre-invasive breast lesions (p < 0.05). Stromagenesis, as characterized by an increase in SMA and a decrease in CD34 positive myofibroblasts was observed mostly around ducts harboring high grade in situ carcinoma and to a lesser extent around moderately differentiated DCIS. In these two groups of in situ carcinomas, a positive correlation between MVD and SMA (p < 0.05) was observed. On the contrary, CD34 was found to be inversely related to MVD (p < 0.05). No statistically significant changes of the stromal fibroblasts were observed in low grade DCIS neither in any of the other lesions under investigation as compared to normal mammary intra- and interlobular stroma. CONCLUSION: Angiogenesis is observed before any significant fibroblastic stromagenesis in pre-invasive breast lesions. A composite phenotype characterized by VEGF positive epithelial cells and SMA positive/CD34 negative stromal cells, is identified mostly in intermediate and high grade DCIS. These findings might imply for new therapeutic strategies using both anti-angiogenic factors and factors selectively targeting tumor stroma in order to prevent the progression of DCIS to invasive carcinoma.

Immunohistochemical localization of interleukin-6 in peripheral human endocrine glands.

Interleukin-6 (IL-6) is a pleiotropic cytokine with differentiation and growth-promoting effects. Extensive studies in experimental animals denote that IL-6 is produced in various endocrine organs and participates in the local control of endocrine cell function. The expression of this cytokine in human endocrine glands, however, has only been examined in a limited number of studies. We investigated the immunohistochemical expression and localization of IL-6 in a variety of peripheral human endocrine glands. In the adrenals, IL-6 immunoreactivity was detected in all three zones of the cortex. The reticularis and glomerulosa zones were more heavily stained as compared with the slight immunoreactivity of the fasciculata zone. In the adrenal medulla, chromaffin and sustentacular cells were variably positive. A substantial number of follicular thyroid cells were strongly immunoreactive for IL-6 in all normal and hyperplastic thyroids examined. Parafollicular cells were negative. Parathyroid chief cells were mildly positive; selective and more intense staining was observed in acidophilic cells. Pancreatic islet cells were variably positive. In the testis positive staining was selectively observed in both Leydig and Sertoli cells. In conclusion, IL-6 immunoreactivity is present in almost all the human endocrine glands and it expressed in a cell-specific manner. These observations provide further support for the existence of local immune-endocrine interactions.

Pituitary corticotroph adenoma containing many apoptotic cells: a histologic, immunohistochemical, ultrastructural and molecular study.

Apoptosis regulates cell turnover in normal tissues and occurs during the neoplastic process. Owing to difficulties in recognizing apoptotic cells by histology alone, several complementary approaches have been introduced, which disclosed the presence of cells with typical nuclear and cytoplasmic changes characteristic of apoptosis. Electron microscopy remains the most conclusive method to reveal the structural changes. Identification of caspase cleaved keratin 18 intermediate filament rearrangements can contribute to the identification of early apoptotic changes. The authors present here an unusual case of a pituitary corticotroph adenoma removed surgically from a young woman with Cushing disease. The tumor contained many apoptotic cells identified by histology. In addition, the apoptotic events were investigated using various morphologic techniques, including electron microscopy, the in situ end-labeling technique, and immunohistochemistry to confirm the caspase-cleaved keratin 18 rearrangements.