GLUT1 expression appears to be an indicator of poor prognosis in DMPM. Standard histological classification of DMPM may not be adequate to select patients for aggressive locoregional treatments, such as CRS and HIPEC. Multicenter validation of the prognostic factors identified in this preliminary study is needed to refine patient selection for potential cure.
Background/Aims: Experimental studies in vitro suggest that somatostatin and some of its analogues used in clinical practice, such as octreotide, may have potent antiangiogenic properties. However, the clinical transposition of these data is difficult. Methods: To address this issue, we designed a comparative study of the effects of somatostatin and octreotide on the interactions between neoplastic endocrine cells and endothelial cells in several in vitro and in vivo experimental models, including primary cultures of human umbilical vein endothelial cells (HUVEC), indirect cocultures between HUVEC and the somatostatin-producing endocrine cell line STC-1, and an animal model of intrahepatic dissemination of STC-1 cells. Results: 10–8M octreotide markedly inhibited both basal and VEGF-stimulated HUVEC proliferation, had no effect on endothelial cell migration, but inhibited endothelial tubule formation. HUVEC cocultured with the somatostatin- and VEGF-producing STC-1 cells presented a markedly decreased proliferation, a slightly increased motility and an increased capacity of tubule formation; in this system, the inhibition of endothelial cell proliferation was abolished by neutralizing anti-somatostatin but was restored in the presence of anti-VEGF antibodies. This suggests that somatostatin is able to antagonize the effects of VEGF on endothelial cell proliferation but not on endothelial cell sprouting. Finally, no significant effect of octreotide on tumor growth and intratumoral microvascular density was detected in an experimental model of intrahepatic dissemination of STC-1 cells. Conclusion: The in vitro antiangiogenic effects of somatostatin and its analogues are likely to be efficiently counterbalanced in the tumor microenvironment by the concomitant release of proangiogenic factors like VEGF.
The presence of pleomorphic tumor giant cells in thyroid carcinomas of follicular cell origin is always worrisome for the pathologist as they first of all refer to anaplastic carcinoma, one of the most aggressive human malignancies. However, non-anaplastic pleomorphic giant cells are well described in other thyroid diseases, most often benign. In this paper, we describe four cases of papillary thyroid carcinoma displaying pleomorphic tumor giant cells with features that differ from those of anaplastic carcinoma. Pleomorphic giant cells were admixed with the underlying thyroid carcinoma and constituted from 5% to 25% of the tumor. Cytologically, they had an abundant eosinophilic cytoplasm with large and irregular nuclei. Compared to pleomorphic giant cells of anaplastic carcinoma, they reproduced the growth pattern of the underlying carcinoma, had a low mitotic index without necrosis or inflammation, and were reactive with thyroglobulin and thyroid-specific transcription factor-1 and strongly and diffusely positive for cytokeratin AE1/AE3. After 16-84 months of follow-up, patients are relapse-free and still alive. These cases show that pleomorphic tumor giant cells arising in papillary thyroid carcinomas do not always represent dedifferentiation and progression to anaplastic carcinoma. Distinction among these processes is critical as their treatment and prognosis are very different.
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