Umeå universitets logga

umu.sePublikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Prognostic factors in renal cell carcinoma: evaluation of erythropoietin and its receptor, carbonic anhydrase IX, parathyroid hormone-related protein and osteopontin
Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
2011 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

A prognostic factor is a marker or a feature that can be used to estimate the risk of recurrence of disease, metastatic spread and clinical outcome. Despite intensive search for more sophisticated markers in renal cell carcinoma (RCC), few have added prognostic information to earlier described factors like stage of disease, nuclear grade, tumour type, and in metastatic disease; performance status, anaemia, hypercalcaemia and increased erythrocyte sedimentation. In the dominating tumour type, clear cell renal RCC (cRCC), hypoxia is common, leading to an up-regulation of hypoxia inducible factor (HIF). The majority of cRCC have a mutation in the von Hippel Lindau gene (VHL-gene), which regulates HIF and in turn leads to up-regulation of a number of target genes for potential growth factors. The aim of the study was to evaluate the possible prognostic information of a few factors associated to pVHL/HIF, anemia and/or hypercalcaemia in RCC; erythropoietin (EPO) and it´s receptor (EPO-R), carbonic anhydrase IX (CA IX), parathyroid hormone-related protein (PTHrP) and osteopontin (OPN).

Patients diagnosed with RCC between 1982-2007 were included in the studies. The tumour tissue expressions of EPO, EPO-R and PTHrP were assessed using immunohistochemistry. Serum/plasma levels of EPO, CA IX, PTHrP and OPN were also analyzed using immunometric methods.

Our study demonstrated that the expression of EPO and EPO-R were related, and the expressions differed significantly between RCC types. The serum EPO levels did not associate to the tumour expression of EPO or EPO-R, indicating that circulating EPO derives from other sources than tumour cells. Erythropietin receptor expression was more frequent in advanced stages of disease, but neither EPO, nor EPO-R, were independent prognostic factors for survival.

Serum CA IX levels were higher in cRCC compared to papillary RCC (pRCC). In cRCC, the CA IX serum levels correlated positively to TNM stage, but serum CA IX did not add independent prognostic information.

Parathyroid hormone-related protein is a cause of hypercalcaemia in malignancy, and we observed that circulating PTHrP related to hypercalcaemia in RCC. The tumour expression of PTHrP associated positively to serum PTHrP, but not to serum calcium. We found an association between PTHrP and OPN in plasma, and both plasma PTHrP and OPN were positively associated to TNM stage.  Neither serum/plasma PTHrP nor tumour expression of PTHrP were independent prognostic factors for survival. The serum OPN levels were higher in pRCC but no impact on survival was observed in this RCC type. In contrast, plasma/serum OPN was an independent prognostic factor for disease-specific survival in cRCC.

Our results support a role for these factors in RCC. The expressions vary between tumour types, which can be explained by different gene aberrations. Some of the factors have a close relation to para-malignant symptoms like hypercalcaemia. Most of the factors correlate positively to TNM-stage, reflecting a relation to advanced disease. Although expression of EPO, EPO-R, PTHrP and CA IX did not add independent prognostic information, the results might contribute to greater understanding of important mechanisms and associations in RCC.

Osteopontin is a strong independent prognostic factor in cRCC, and should be further evaluated as a tool in the clinic when treating RCC patients.

Ort, förlag, år, upplaga, sidor
Umeå: Umeå universitet , 2011. , s. 48
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1400
Nyckelord [en]
Renal cell carcinoma, EPO, EPO-R, CA IX, PTHrP, OPN, prognosis
Nationell ämneskategori
Cancer och onkologi
Forskningsämne
onkologi
Identifikatorer
URN: urn:nbn:se:umu:diva-40047ISBN: 978-91-7459-145-3 (tryckt)OAI: oai:DiVA.org:umu-40047DiVA, id: diva2:397861
Disputation
2011-03-11, Bergasalen, Byggnad 27, Norrlands universitetssjukhus, Umeå, 09:00 (Svenska)
Opponent
Handledare
Tillgänglig från: 2011-02-21 Skapad: 2011-02-15 Senast uppdaterad: 2018-06-08Bibliografiskt granskad
Delarbeten
1. Parathyroid hormone-related protein and serum calcium in patients with renal cell carcinoma
Öppna denna publikation i ny flik eller fönster >>Parathyroid hormone-related protein and serum calcium in patients with renal cell carcinoma
2005 (Engelska)Ingår i: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 26, nr 4, s. 201-206Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Objective: To evaluate serum parathyroid hormone-related protein (PTHrP) in relation to serum calcium and clinical outcome of patients with renal cell carcinoma.

Methods: Sera from 243 patients with renal cell carcinoma were collected prior to therapy. Serum PTHrP was analyzed using an immunoradiometric assay. Tumour stage, nuclear grade, corrected serum calcium, and survival were assessed.

Results: Serum PTHrP was detectable in 37/243 sera (15%) and hypercalcaemia (≥2.60 mmol/l) in 32/220 (15%). A positive correlation between serum PTHrP and serum calcium was found (r = 0.326; p < 0.01). Following subdivision of the material, based on storage time, the frequency of detectable serum PTHrP seemed to decrease with time. Serum calcium, but not serum PTHrP, was correlated to tumour stage (p < 0.001). Survival was similar for patients with detectable and undetectable PTHrP, but those with hypercalcaemia had a significantly shorter survival time compared to those with normal serum calcium (p < 0.001). A multivariate analysis showed that tumour stage and serum calcium were independent prognostic factors, but not grade or PTHrP.

Conclusions: A positive relation of serum PTHrP to serum calcium was demonstrated in patients with renal cell carcinoma. Hypercalcaemia but not serum PTHrP predicted a worse prognosis.

Nyckelord
Parathyroid hormone-related protein, calcium, serum, hypercalcaemia, renal cell carcinoma, prognosis
Nationell ämneskategori
Cancer och onkologi
Forskningsämne
onkologi
Identifikatorer
urn:nbn:se:umu:diva-14553 (URN)10.1159/000086953 (DOI)16006777 (PubMedID)2-s2.0-24644437843 (Scopus ID)
Tillgänglig från: 2007-09-14 Skapad: 2007-09-14 Senast uppdaterad: 2023-03-24Bibliografiskt granskad
2. Expression of erythropoietin and its receptor in human renal cell carcinoma
Öppna denna publikation i ny flik eller fönster >>Expression of erythropoietin and its receptor in human renal cell carcinoma
Visa övriga...
2009 (Engelska)Ingår i: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 30, nr 2, s. 86-92Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Objective: To investigate the prognostic impact of erythropoietin (EPO) and EPO-receptor (EPO-R) expression in tumour as well as serum EPO in patients with renal cell carcinoma (RCC).

Methods: Using immunohistochemistry, EPO and EPO-R were assessed in tissue microarrays from 195 RCCs. RCC type, TNM stage, nuclear grade, survival, EPO and haemoglobin (Hb) levels in blood were registered.

Results: Strong expression of EPO and EPO-R in tumour tissue was found in 83 and 56%, respectively. EPO and EPO-R expression differed between RCC types. Serum EPO and blood Hb did not correlate to the expression of EPO or EPO-R. A positive correlation was found between the expression of EPO and EPO-R (p = 0.028). Survival was not related to tumour EPO, whereas strong EPO-R expression indicated a non-significantly worse prognosis. Serum EPO correlated positively to TNM stage and nuclear grade and negatively to survival. A multivariate analysis showed that TNM stage and nuclear grade were independent prognostic factors. Tumour EPO and EPO-R expression as well as serum EPO added no independent prognostic information.

Conclusion: No correlation between EPO or EPO-R in tumour tissue and serum EPO or blood Hb was found. Neither EPO, EPO-R in tumour tissue nor serum EPO are independent prognostic factors.

Nationell ämneskategori
Cancer och onkologi
Forskningsämne
onkologi
Identifikatorer
urn:nbn:se:umu:diva-22455 (URN)10.1159/000216844 (DOI)19407488 (PubMedID)2-s2.0-65449187188 (Scopus ID)
Tillgänglig från: 2009-05-11 Skapad: 2009-05-11 Senast uppdaterad: 2023-03-23Bibliografiskt granskad
3. Soluble carbonic anhydrase IX is not an independent prognostic factor in human renal cell carcinoma
Öppna denna publikation i ny flik eller fönster >>Soluble carbonic anhydrase IX is not an independent prognostic factor in human renal cell carcinoma
Visa övriga...
2010 (Engelska)Ingår i: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 30, nr 7, s. 2953-2957Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The aim of this study was to evaluate the prognostic information of soluble carbonic anhydrase (CA) IX expression in renal cell carcinoma (RCC).

PATIENTS AND METHODS: Serum CA IX was analysed in 361 patients. Tumour type, TNM stage, nuclear grade, and RCC-specific survival were assessed. Serum and immunohistochemical expression were compared.

RESULTS: Median serum CA IX expression was 141 (range 2-4, 181) pg/ml. Levels were significantly higher in 287 patients with clear cell, compared to 40 papillary (p<0.001) and 22 oncocytoma (p=0.002), but not to 12 chromophobe RCC (p=0.35). Serum CA IX in clear cell RCC was positively correlated to TNM stage (p=0.002). There was a positive trend between serum and immunohistochemical CA IX expression. In a multivariate analysis of clear cell RCC, TNM stage and nuclear grade were independent prognostic factors.

CONCLUSION: Serum CA IX was higher in clear cell RCC compared to other RCC types. In clear cell RCC, serum CA IX correlated to TNM stage, but not survival.

Ort, förlag, år, upplaga, sidor
International Institute of Anticancer Research, 2010
Nyckelord
Carbonic anhydrase IX, renal cell carcinoma, prognosis
Nationell ämneskategori
Cancer och onkologi
Forskningsämne
onkologi
Identifikatorer
urn:nbn:se:umu:diva-35336 (URN)000280796400067 ()20683038 (PubMedID)2-s2.0-77955824501 (Scopus ID)
Tillgänglig från: 2010-08-13 Skapad: 2010-08-13 Senast uppdaterad: 2023-03-24Bibliografiskt granskad
4. Osteopontin and parathyroid hormone-related protein in human renal cell carcinoma
Öppna denna publikation i ny flik eller fönster >>Osteopontin and parathyroid hormone-related protein in human renal cell carcinoma
Visa övriga...
(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Nationell ämneskategori
Cancer och onkologi
Forskningsämne
onkologi
Identifikatorer
urn:nbn:se:umu:diva-39979 (URN)
Tillgänglig från: 2011-02-11 Skapad: 2011-02-11 Senast uppdaterad: 2018-06-08Bibliografiskt granskad

Open Access i DiVA

fulltext(2429 kB)1863 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 2429 kBChecksumma SHA-512
49c332061779ff9aea7f835e1fa3abb483f926f1d8886c40b5276318513eabe7810ae0e6320094d5c5074070a35592fa0e07bfdffbf2fdb322adedcbd5c84c03
Typ fulltextMimetyp application/pdf

Person

Papworth, Karin

Sök vidare i DiVA

Av författaren/redaktören
Papworth, Karin
Av organisationen
Onkologi
Cancer och onkologi

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 1892 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

isbn
urn-nbn

Altmetricpoäng

isbn
urn-nbn
Totalt: 958 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf