Inflammatory breast cancer shows angiogenesis with high endothelial proliferation rate and strong E-cadherin expression.
Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. Improved understanding of the mechanisms responsible for the differences between IBC and non-IBC might provide novel therapeutic targets. We studied 35 consecutive patients with IBC, biopsied prior to the initiation of chemotherapy. Angiogenesis was evaluated by Chalkley counting and by assessment of endothelial cell proliferation (ECP) and vessel maturity. The presence of fibrin, expression of the hypoxia marker carbonic anhydrase IX (CA IX) and epithelialcadherin (E-cadherin) expression were immunohistochemically detected. The same parameters were obtained in a group of 104 non-IBC patients. Vascular density, assessed by Chalkley counting (P<0.0001), and ECP (P=0.01) were significantly higher in IBC than in non-IBC. Abundant stromal fibrin deposition was observed in 26% of IBC and in only 8% of non-IBC (P=0.02). Expression of CA IX was significantly less frequent in IBC than in non-IBC with early metastasis (P=0.047). There was a significant positive correlation between the expression of CA IX and ECP in IBC (r=0.4, P=0.03), implying that the angiogenesis is partly hypoxia driven. However, the higher ECP in IBC and the less frequent expression of CA IX in IBC vs non-IBC points at a role for other factors than hypoxia in stimulating angiogenesis. Strong, homogeneous E-cadherin expression was found at cell-cell contacts in all but two IBC cases, both in lymphovascular tumour emboli and in infiltrating tumour cells, challenging our current understanding of the metastatic process. Both the intense angiogenesis and the strong E-cadherin expression may contribute to the highly metastatic phenotype of IBC.
Colpaert
C G
CG
Department of Pathology, University Hospital Antwerp, Edegem, Belgium. Cecile.Colpaert@uza.be
Vermeulen
P B
PB
Benoy
I
I
Soubry
A
A
van Roy
F
F
van Beest
P
P
Goovaerts
G
G
Dirix
L Y
LY
van Dam
P
P
Fox
S B
SB
Harris
A L
AL
van Marck
E A
EA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000098:blood supply* / Q000201:enzymology / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D002256:Carbonic Anhydrases / Q000378:metabolism; D002455:Cell Division; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D009389:Neovascularization, Pathologic
D015820:Cadherins; D005337:Fibrin; D002256:Carbonic Anhydrases