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Altered pigment epithelium-derived factor and vascular endothelial growth factor levels in lymphangioma pathogenesis and clinical recurrence.

OBJECTIVE
To determine the role of angiogenesis in the clinical behavior and pathogenesis of lymphangioma tumors.


DESIGN
A retrospective study. Median follow-up period was 44.5 months.


SETTING
Children's Memorial Hospital, Chicago, Ill.


PATIENTS
Tumor specimens from 12 pediatric patients who underwent surgical excision of cervicofacial lymphangioma were examined for expression of angiogenic inducer vascular endothelial growth factor (VEGF) and angiogenic inhibitor pigment epithelium-derived factor (PEDF) using immunohistochemical analysis. Specimens were divided into recurrent and nonrecurrent tumors based on clinical information.


MAIN OUTCOME MEASURES
Staining patterns of VEGF and PEDF were evaluated in lymphangioma specimens. Staining patterns were then compared in both recurrent and nonrecurrent groups and graded in a blinded fashion. Histological evidence of increased angiogenesis including microvascular density, stromal fibrosis, and inflammation were graded in each group and correlated with recurrence.


RESULTS
Lymphangioma specimens demonstrated histological evidence of increased angiogenic activity including multiple areas of increased VEGF staining combined with little PEDF staining. Sex, age at onset, or tumor location did not correlate with recurrence. Furthermore, recurrent specimens had increased histological evidence of angiogenesis as well as increased VEGF and decreased PEDF activity compared with nonrecurrent lesions.


CONCLUSIONS
Lymphangiomas exhibit tumorlike pathogenesis owing to the high expression of angiogenic inducers compared with the low expression of inhibitors. Recurrence may be influenced by this imbalance of angiogenic mediators. Further research with antiangiogenic therapy using agents such as PEDF analogues or anti-VEGF receptor antibodies is indicated because they may stabilize or suppress the growth of these neoplasms.