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Expression of angiogenic VEGF‐A (soluble isoforms 121, 165) and lymphangiogenic VEGF‐C in colorectal cancers with micro‐satellite instability
Author(s) -
Hollingsworth Simon J.,
Drye Elizabeth R.,
Tou Samson I.H.,
Boulos Paul B.
Publication year - 2005
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.20321
Subject(s) - medicine , vegf receptors , colorectal cancer , cancer research , angiogenesis , gene isoform , oncology , pathology , cancer , biology , gene , biochemistry
Background and Objectives Colorectal cancers (CRC) with high‐level micro‐satellite instability (MSI‐H) show reduced metastatic potential and better prognosis compared to stage‐matched stable (MSS) cancers. Angiogenesis/lymphangiogenesis, central to tumour growth and spread, is mediated by vascular endothelial growth factor (VEGF) cytokines, but little is known of their relationship to MSI. Methods In this study, 67 sporadic CRC with identified MSI status, and 8 samples of normal colon were analysed for VEGF‐A soluble isoforms (VEGF‐121/VEGF‐165) and VEGF‐C gene transcription (by RT‐PCR and scanning densitometry), and blood vessel density (BVD; measuring angiogenesis) and VEGF‐C protein expression (measuring lymphangiogenesis). Results Compared to normal colon, VEGF‐165 transcription was reduced ( P < 0.05), but VEGF‐121 transcription was higher in MSS ( P < 0.06) and MSI‐L ( P < 0.01) cancers (but similar in MSI‐H). VEGF‐165 transcription was unrelated to MSI, but VEGF‐121 transcription was elevated in MSI‐L ( P < 0.06). There was a weak inverse correlation with VEGF‐121 transcription and Dukes stage ( P < 0.09), and with BVD and MSI ( P < 0.09). With a singular di‐nucleotide loci mutation (MSI‐L), VEGF‐121 ( P < 0.03) and VEGF‐C ( P < 0.04) transcription was elevated. Conclusions MSI‐H cancers have reduced angiogenic/lymphangiogenic potential, and transcription of VEGF‐121 may be important in early growth and spread of CRC. Elevated VEGF‐121 and VEGF‐C transcription with singular di‐nucleotide mutations may aid in the identification of distinct MSI‐L cancers. J. Surg. Oncol. 2005;92:317–325. © 2005 Wiley‐Liss, Inc.