cyclin-d1 and Hemangioma

Infantile hemangioma (IH) is the most common tumor of infancy. The first-line therapy for IH is propranolol, a nonselective β-adrenergic receptor antagonist. However, mechanisms for the therapeutic effect of propranolol and regrowth of IH following cessation of treatment in some cases are not clear. We have recently shown that IH arises from multipotent stem cells. Whether IH stem cells are responsive to propranolol and are selectively targeted is unknown, and this is the focus of this study.. IH stem cells were exposed to propranolol and were assayed for cellular and molecular alterations. We used endothelial cells (ECs) as controls and bone marrow-derived mesenchymal progenitor cells (bm-MPCs) as normal stem/progenitor counterparts to determine selectivity.. Our results show that propranolol significantly reduced IH stem cell growth but failed to induce caspase-3 activation. Normal bm-MPCs and mature ECs showed maintained or increased caspase-3 activation and significantly reduced cyclin-D1 levels. We further show that IH stem cells may escape apoptosis by inducing antiapoptotic pathways.. This study reveals that propranolol does not induce apoptosis in IH stem cells, which is in contrast with the result for ECs. Escape from apoptosis in IH stem cells may involve induction of antiapoptotic pathways.

Topics: Adrenergic beta-Antagonists; Apoptosis; Caspase 3; Cell Count; Cell Proliferation; Cyclin D1; Hemangioma; Humans; Infant; Multipotent Stem Cells; Propranolol; Real-Time Polymerase Chain Reaction

Cyclin D1 gene amplification has been reported to promote abnormal endothelial cell proliferation and angiogenesis; these findings constantly present in proliferating haemangiomas. The present study was conducted to evaluate cyclin D1 gene amplification by fluorescence in situ hybridization analysis in tissue biopsies of 22 proliferating haemangiomas from 20 infants. Two significant correlations of cyclin D1 gene amplification with the early onset and the duplication of proliferating haemangiomas have been observed. Moreover, a significant correlation (P< or =0.05) has been found between the treatment parameters of proliferating haemangiomas with the amplified versus the normal cyclin D1 gene. Proliferating haemangiomas with the amplified cyclin D1 gene required more frequent flashlamp pulsed dye laser treatment sessions at the maximum dosimetry and more frequent intralesional steroid injections at the maximum dose/injection but treatment outcomes were limited. The more frequent post-treatment complications among proliferating haemangiomas with cyclin D1 gene amplification might be attributable not only to the associated more aggressive natural course, but also to the higher treatment parameters needed for effective treatment. Within the limitations of the present study, cyclin D1 gene amplification was seen for the first time in proliferating haemangiomas. We have found that the amplification of the cyclin D1 gene can predict the more aggressive natural course of proliferating haemangiomas and the limited outcome and higher incidence of complications after non-excision treatment modalities. The present findings reflect the possible usefulness of antisense cyclin D1 to improve the therapeutic outcome of proliferating haemangiomas.

Topics: Biopsy; Cyclin D1; Female; Gene Amplification; Genes, bcl-1; Hemangioma; Humans; In Situ Hybridization, Fluorescence; Infant; Laser Therapy; Male; Steroids

Vascular tumors comprise a minor subgroup of tumors arising in the breast and represent variants of hemangiomas and angiosarcomas. Diagnostic challenges may arise when differentiating hemangiomas from types I and II angiosarcomas. Ki-67 expression has been used as an adjunct to distinguish between benign and malignant lesions exhibiting histologic overlap at various anatomic sites.. To investigate the utility of Ki-67 and other cell cycle regulatory proteins (S-phase kinase-associated protein 2 [Skp2], p27, and cyclin D1) in the differential diagnosis of mammary vascular lesions.. Thirty-four vascular tumors (21 hemangiomas and 13 angiosarcomas) of the breast were studied. The Ki-67 index and immunoreactivity for Skp2, p27, and cyclin D1 were determined in each case. Appropriate statistical methods were used.. The mean value of Ki-67 index was statistically different when comparing hemangiomas and angiosarcomas (P < .001). Angiosarcomas were typically positive for Skp2, whereas hemangiomas were negative (P < .001). Sensitivity and specificity cutoffs for Ki-67 index to distinguish hemangiomas from angiosarcomas showed a candidate cutoff point of 175. The mean values of Ki-67 of low-grade angiosarcomas were significantly different from all hemangiomas (P < .001) and also different from the subset of atypical hemangiomas (P = .02). Sensitivity and specificity cutoffs for Ki-67 index to distinguish all hemangiomas from low-grade angiosarcomas showed a candidate cutoff point between 150 and 175. Among angiosarcomas, positivity for Ki-67 was inversely related to that of p27 but not to Skp2 or cyclin D1. This was also true among hemangiomas.. Ki-67 index can be used as a diagnostic tool to distinguish between benign and malignant vascular lesions of the breast. This can be particularly helpful in cases of histologic overlap such as low-grade angiosarcoma and hemangioma.

Topics: Biomarkers, Tumor; Breast Neoplasms; Breast Neoplasms, Male; Cell Cycle; Cyclin D1; Diagnosis, Differential; Female; Hemangioma; Hemangiosarcoma; Humans; Immunohistochemistry; Ki-67 Antigen; Male; Middle Aged; Proliferating Cell Nuclear Antigen; S-Phase Kinase-Associated Proteins; Sensitivity and Specificity