Late onset of bortezomib-associated cutaneous reaction following herpes zoster.
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Biomedical subjects
Publications and source records attributed to Renato Rosso.
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CONTEXT: CD31 (platelet-endothelial cell adhesion molecule-1; PECAM-1), an adhesion molecule involved in the process of angiogenesis, is used as a marker of normal and neoplastic vascularization. During the assessment of angiogenesis and vascular invasion in a thymic carcinoid tumor, we observed unexpected immunostaining for CD31 in perithymic brown fat nests. OBJECTIVE: To determine whether CD31 is expressed by normal and neoplastic cells of brown fat, a tissue whose thermogenetic activity depends heavily on high perfusion. DESIGN: Formalin-fixed, paraffin-embedded archival tissues were immunostained by the labeled avidin-biotin method using antibodies against CD31 (clones JC70A and 1A10) after retrieval of heat-induced epitopes. Archival tissues included perithymic, periadrenal, axillary, and neck adipose tissue in which were embedded nests of brown fat (n = 15), hibernoma (n = 3), lipoma (n = 6), well-differentiated liposarcoma (n = 4), and myxoid liposarcoma (n = 4). RESULTS: Invariably, multivacuolated and univacuolated adipocytes of normal brown fat and hibernomas were intensely positive for the CD31 antigen. The immunostaining "decorated" cell membranes and the membranes of intracytoplasmic vacuoles. No expression of CD31 was found in normal adipocytes of white fat, in neoplastic cells of lipomas, or in multivacuolated lipoblasts of well-differentiated and myxoid liposarcomas. CONCLUSIONS: The spectrum of cell types that express CD31 is expanded to include normal and neoplastic brown fat cells. We speculate that the expression of CD31 may play a role in the development and maintenance of the vascular network characterizing this specialized adipose tissue. Moreover, CD31 may inhibit the Bax-mediated apoptosis of brown fat cells. For practical purposes, CD31 may be used as an immunohistochemical marker for distinguishing between white and brown fat and for diagnosing hibernoma in paraffin sections.
The fourth case in the literature is presented of a patient with the rare association of hyperparathyroidism and osteosarcoma. A 56-year-old woman presented with hyperparathyroidism and a lesion in the tibia. Initial diagnosis was brown tumor. Histology, however, revealed osteosarcoma, and the patient was treated accordingly. The experimental induction of osteosarcoma by parathormone in rodent studies makes this finding alarming, considering the increasing use of parathormone in the treatment of osteoporosis. The mechanism by which osteosarcoma is induced in humans cannot be explained based on current knowledge of mechanisms of action of parathyroid hormone.
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The proto-oncogene product Ron is the receptor for macrophage stimulating protein, a scatter factor that stimulates cell proliferation, prevents apoptosis, and induces an invasive cell phenotype. We investigated the expression of Ron, Ki-67 (proliferation index), p53, and bcl-2 (proapoptotic and antiapoptotic proteins, respectively) in 50 renal tumors (19 clear cell carcinomas, 18 oncocytomas, 7 papillary cell carcinomas, 5 chromophobe cell carcinomas, and 1 carcinoma with sarcomatoid areas). In addition, we studied Ron in normal kidney and in the renal carcinoma cell line Caki-1. Immunostaining and Western blot showed Ron in normal kidney and in all oncocytomas but never in renal cell carcinomas or in Caki-1. In addition, Western blot showed that Ron was expressed in phosphorylated, i.e., active, form. Bcl-2 was strongly expressed in oncocytomas, whereas Ki-67 and p53 were much less expressed in oncocytomas than in carcinomas. These results indicate in Ron a marker that differentiates oncocytoma from the other renal epithelial tumors. We therefore think that Ron may prove to be a new tool for a sound and precise diagnosis of oncocytoma, a benign tumor that cannot always be distinguished from carcinomas at histologic examination. The overexpression of bcl-2, but not p53 in oncocytoma, suggests that the MSP/Ron system sustains the growth of oncocytoma by opposing apoptosis.
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