Clusterin/ApoJ expression during the development of hemangioma

Hemangioma is the most common tumor of infancy. This vascular tumor is char acterized by an initial rapid proliferation followed by an inevitable regre ssion. The life cycle of hemangioma is divided into proliferative, involuti ng, and involuted phases. The cellular and molecular mechanisms responsible for controlling the biological behavior of hemangioma are largely unknown. Differential display analysis using mRNA isolated from biopsy specimens re presentative of the 3 different phases showed increased expression of clust erin/apoJ (clust/apoJ) in the involuting samples. Clust/apoJ is a multifunc tional glycoprotein that has been associated with apoptosis. Reverse transc ription-polymerase chain reaction (RT-PCR) and immunohistochemistry showed that both the transcription and protein expression of clust/apoJ were incre ased in hemangioma as the tumor progressed from the proliferative to the in voluting and involuted phases. This suggests that clust/apoJ is involved in regulating apoptosis during the spontaneous regression of hemangioma. It h as been suggested that mast cells (MC) play a role in the regression of hem angioma. The increase in the number and proportion of clust/apoJ-positive M C with progression of hemangioma, along with the localization of clust/apoJ to MC granules, supports this hypothesis. We suggest that MC may be synthe sizing/releasing this apoptotic modulator, leading to the regression of the tumor. Better understanding of the pathogenesis of hemangioma by identific ation of the relevant factors involved in its regression such as clust/apoJ will result in the development of novel therapies for this condition and t umors that do not undergo spontaneous regression. HUM PATHOL 31:691-697, Co pyright (C) 2000 by W.B. Saunders Company.