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Altered Pigment Epithelium–Derived Factor and Vascular Endothelial Growth Factor Levels in Lymphangioma Pathogenesis and Clinical Recurrence
Douglas M. Sidle, MD;
John Maddalozzo, MD;
Jason D. Meier, MD;
Mona Cornwell, HT(ASCP);
Veronica Stellmach, PhD;
Susan E. Crawford, MD
Arch Otolaryngol Head Neck Surg. 2005;131:990-995.
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.
Author Affiliations: Departments of Otolaryngology–Head and Neck Surgery (Drs Sidle, Maddalozzo, and Meier) and Pathology (Ms Cornwell and Drs Stellmach and Crawford), Northwestern University Feinberg School of Medicine, and Division of Pediatric Otolaryngology, Children’s Memorial Hospital (Dr Maddalozzo), Chicago, Ill.
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