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UID:20260712T105638EDT-386028iO6I@132.216.98.100
DTSTAMP:20260712T145638Z
DESCRIPTION:Background: Angiogenesis plays an important\nrole in the progre
 ssion of solid tumors\, providing both nutrients\nrequired for growth and 
 a way to escape the tumor bed. The level of\nvascularization\, as measured
  by microvessel density\, varies greatly\nbetween breast cancer patients. 
 A high microvessel density\nsignificantly predicts poor survival in breast
  cancer\, but\nbetween-study variation is high. It is also known that the 
 tumor\nvasculature differs significantly from its normal counterpart.\nAmo
 ng other changes\, it is often leaky and generally less mature\,\nlacking 
 the functional pericytes that help stabilize the vessels.\nExploitation of
  these differences has led to the development of\nseveral therapeutic aven
 ues to target the tumor vasculature\, most\nnotably antivascular endotheli
 al growth factor therapy. Several\nstudies have helped characterize the ge
 ne expression of tumor\nendothelial cells in different cancers and identif
 y tumor-specific\nendothelial markers. However\, none had sufficient sampl
 es to\ninvestigate the variations that exist between patients.\nMethods: T
 o study endothelial gene expression\,\nwe performed microarray hybridizati
 on (N=32) of laser capture\nmicrodissected endothelial cells from invasive
  ductal carcinomas\nand matched endothelial morphologically normal adjacen
 t tissue. We\nused various statistical techniques to analyze the data and 
 compare\nit with the additional datasets from the published literature.\nI
 mmunohistochemistry and polymerase chain reaction were used to\nvalidate t
 he results.\nResults: We identified two distinct subtypes of\ntumor endoth
 elial cells in breast cancer patients. They are\nassociated with tumors of
  high and low vascular density but not\nwith recurrence. The gene expressi
 on and immunohistochemistry of\npericyte markers offer evidence that the s
 ubtypes are also\nassociated with vessel maturity. Surprisingly\, most of 
 the\npublished markers of tumor endothelial cells are specifically\nassoci
 ated with the low vascular density group. We also identified\ndifferences 
 in the Notch and transforming growth factor-beta\nsignaling pathways. Usin
 g the information from the subtypes\, we\ndeveloped a prognostic predictor
  of recurrence based on tumor\nvascular gene expression. Interestingly\, t
 his is independent of the\nmicrovessel density\, identifying the recurrenc
 es in high and low\ndensity patients. The genes in this predictor are link
 ed to several\npathways linked to DNA repair\, apoptosis\, and energy\npro
 duction.\nRelevance: This project will help us clarify\nour understanding 
 of the process of vascularization in breast\ncancer and its role in tumor 
 progression and metastasis. The\nidentification of distinct tumor endothel
 ial classes will help\nclarify the complex role that the vasculature plays
  in tumor\nprogression. Our prognostic predictor reinforces that view and
 \nidentifies differences in tumor vascular gene expression can be\nlinked 
 to distant recurrences. This differential expression points\nto pathways t
 hat could be involved in metastasis. This could lead\nto more individualiz
 ed and potentially new treatment options.\n
DTSTART:20081022T183000Z
DTEND:20081022T200000Z
LOCATION:McIntyre Medical Building\, CA\, QC\, Montreal\, H3G 1Y6\, 3655 pr
 omenade Sir William Osler
SUMMARY:Transcriptional profile of vascular tissue identifies distinct subt
 ypes of vasculature and predicts clinical outcome in breast cancer
URL:/channels/event/transcriptional-profile-vascular-t
 issue-identifies-distinct-subtypes-vasculature-and-predicts-clinic-102197
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