Angiogenesis in human renal cell carcinoma: hypoxia, vascularity and prognosis

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Fältnamn	Indikatorer	Metadata
000		04945nam a2200505 4500
001		oai:DiVA.org:umu-1331
003		SwePub
008		070903s2007 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
020		a 9789172643154q print
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-13312 URI
040		a (SwePub)umu
041		a engb eng
042		9 SwePub
072	7	a vet2 swepub-contenttype
072	7	a dok2 swepub-publicationtype
100	1	a Sandlund, Johanna,d 1979-u Umeå universitet,Institutionen för strålningsvetenskaper4 aut
245	1 0	a Angiogenesis in human renal cell carcinoma :b hypoxia, vascularity and prognosis
264	1	a Umeå :b Strålningsvetenskaper,c 2007
300		a 64 s.
338		a electronic2 rdacarrier
490	0	a Umeå University medical dissertations,x 0346-6612 ;v 1100
520		a Background: Angiogenesis is recognised as a critical step in tumour progression. The angiogenic switch is activated by various trigger signals, such as hypoxia, low pH, and genetic mutations. Renal cell carcinoma (RCC) is often an aggressive tumour, and advanced disease has limited treatment options and bad prognosis. This study was focused on markers of angiogenesis in RCC: endoglin (CD105) and CD31 assessing microvessel density (MVD), and carbonic anhydrase (CA) IX and hypoxia-inducible factor (HIF)-2α expressed at hypoxia. Upregulation of HIF is also associated with inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene, which is common in conventional/clear cell (c)RCC. Method: A tumour bank containing 308 tumours from patients operated 1982-2003 was used. The tumours were well characterised regarding tumour type, TNM stage, nuclear grade, tumour size, and patient survival. The tumours were prepared in tissue microarrays and fresh frozen in whole sections. To analyse the expression of endoglin, CD31, CA IX, and HIF-2α mRNA, immunohistochemistry and real-time PCR were used. Results: There was a higher endoglin expression in cRCC than in papillary (p)RCC and chromophobe (ch)RCC, and a higher CD31 expression in cRCC than in pRCC. MVD correlated inversely to TNM stage and nuclear grade in cRCC. There was also an inverse correlation between tumour diameter and CD31 expression in cRCCs. Patients with cRCC with high MVD had a more favourable prognosis than patients with lower MVD. Endoglin and CD31 were not independent prognostic factors. The CA IX expression was higher in cRCC than in pRCC and chRCC. Patients with cRCC expressing low CA IX had a significantly less favourable prognosis compared with those with higher expression. CA IX is an independent prognostic factor. There was a higher HIF-2α mRNA expression in cRCC than in pRCC and chRCC. In cRCC, there was a significant inverse correlation between HIF-2α mRNA expression, and TNM stage and nuclear grade. There was also an inverse correlation between HIF-2α mRNA expression and tumour size among patients with cRCC. HIF-2α was not an independent prognostic factor. Conclusion: In these studies, the factors related to hypoxia and vascularity were all inversely correlated to tumour aggressiveness in cRCC. MVD, CA IX, and HIF-2α expression were also higher in cRCC than in pRCC and chRCC. The relationship between angiogenesis, vascularity, and hypoxia is ambiguous. A line of reasoning including mutations increasing angiogenesis in advanced disease may also be applied to RCC. Measurements of individual angiogenic factors seem to provide prognostic information, and can potentially be combined in patient monitoring and treatment.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng
653		a Endoglin/CD105
653		a CD31
653		a prognosis
653		a CA IX
653		a HIF-2α
653		a renal cell carcinoma
653		a tissue microarray
653		a immunohistochemistry
653		a real-time PCR
653		a stage
653		a grade
653		a Oncology
653		a Onkologi
700	1	a Rasmuson, Torgny,c Docentu Umeå universitet,Institutionen för strålningsvetenskaper4 ths
700	1	a Ljungberg, Börje,c Professoru Umeå universitet,Institutionen för kirurgisk och perioperativ vetenskap4 ths
700	1	a Grankvist, Kjell,c Professoru Umeå universitet,Institutionen för medicinsk biovetenskap4 ths
700	1	a Bergh, Anders,c Professoru Umeå universitet,Institutionen för medicinsk biovetenskap4 ths
700	1	a Kjellén, Elisabeth,c Docentu Onkologiska klin, Universitetssjukhuset i Lund4 opn
710	2	a Umeå universitetb Institutionen för strålningsvetenskaper4 org
856	4	u https://umu.diva-portal.org/smash/get/diva2:140677/FULLTEXT01.pdfx primaryx Raw objecty fulltext
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1331

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Av författaren/redakt...: Sandlund, Johann ...; Rasmuson, Torgny ...; Ljungberg, Börje ...; Grankvist, Kjell ...; Bergh, Anders, P ...; Kjellén, Elisabe ...

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Av lärosätet: Umeå universitet

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