Chorioangiomas are benign angiomatous tumours of the placenta occurring with a frequency of approximately one per cent of all examined placentae.
Hypoxia and genetic factors are discussed to be predisposing factors for
chorioangiomas. However, not much is known about the
tumorigenesis of these benign tumours. Screening with various
antibodies in a rare case of chorangiomatosis, we found disseminated spindle cells coexpressing vascular epithelial
growth factor (
VEGF),
neutral endopeptidase 24.11 (NEP/CD10), and KIT
protein (CD117) within the tumour stroma. A possible involvement of such factors in angiogenesis and
tumorigenesis of
chorioangiomas/chorangiomatosis has not been studied so far.Seven placentae with
chorioangiomas (n=6) or chorangiomatosis (n=1), six normal placentae, and four cutaneous haemangiomas were analysed immunohistochemically (ABC and APAAP methods) using
antibodies against
VEGF, NEP, KIT
protein, as well as endothelial markers like
PECAM-1 (CD31), CD34, v. Willebrand factor (
factor VIII), and ulex europaeus. In addition, analysis of c-kit 'gain of function' mutation Asp 816 to Val by means of Hinfl digestion and direct sequencing of semi-nested polymerase chain reaction products was performed. All
chorioangiomas and haemangiomas strongly expressed the endothelial markers CD34, CD31, and FVIII, while only weak expression of
ulex lectin was noted. Disseminated groups of
VEGF-, NEP-, and KIT
protein-positive spindle cells, which coexpressed
vimentin and smooth-muscle actin were identified as myofibroblasts in the stroma of four
chorioangiomas. These spindle cells were quantified as numerous in two and as rare in two other cases. No
VEGF-positive myofibroblasts, however, were detected in the villous stroma of normal control placentae and haemangiomas. Only scattered perivascular myofibroblasts expressing KIT
protein and NEP were detected in early gestational placenta controls. In all
chorioangiomas and chorangiomatosis PCR analysis failed to unveil c-kit 'gain of function' mutation Asp 816 to Val in KIT
protein-positive spindle cells. Moreover, a significant increase in mast cells was observed only in the haemangiomas. As expected, endothelial origin of
chorioangiomas/chorangiomatosis was verified by CD31, CD34, FVIII expression. Myofibroblastic spindle cells expressing
VEGF and NEP may be precursor cells in these peculiar angiomatous tumours. Although activating c-kit mutation Asp 816 to Val was not detected by PCR, the presence of KIT
protein (CD117)-positive intratumoral myofibroblastic spindle cells in
chorioangiomas and chorangiomatosis might suggest involvement of the
stem cell factor (
SCF)-receptor in pathologically enhanced angiogenesis.