Do insulin-like growth factor associated proteins qualify as a tumor marker? results of a prospective study in 163 cancer patients*

Flehmig B, Knoefel Wt, Prisack Hb, Shukla V, Kammers K, Scherer A, Schauer M, Matuschek G, Rudoy M, Peiper M, Gerber Pa, Hoff Np, Buhren Ba, Budach W, Bojar H, Steinbach G, Schwarz A, Erhardt A, Bölke E

Description

Objective Insulin-like growth factor (IGF)-1, -2 and Insulin like growth factor binding proteins (IGFBP) are involved in the proliferation and differentiation of cells. It has never been evaluated, if the IGF-system can serve as a tumor marker in neoplasms. Methods In our prospective study 163 patients with colorectal cancer (22), prostate cancer (21), head and neck tumors (17), lymphomas (20), lung cancer (34) and other entities (49) were analysed for their IGF and IGFBP serum levels at the beginning and the end of radiotherapy and compared to 13 healthy people. Subgroups of patients with local tumor disease versus metastatic disease, primary and recurrent therapy and curative versus palliative therapy were compared. Results The serum levels of IGF-2 were significantly elevated in patients with prostate and colorectal cancer. However, sensitivity and specificity were only 70%. IGFBP-2 serum levels were elevated in patients with head and neck tumors. Again sensitivity and specificity were only 73%. A difference between local disease and metastatic disease could not be found. A difference between IGF serum levels before and after radiotherapy could not be detected. Conclusion The IGF-system cannot serve as a new tumor marker. The detected differences are very small, sensitivity and specificity are too low. IGF measurement is not useful for the evaluation of the success of radiotherapy in malignancies.

Sujets

• Insulin-like growth factor
• Tumor marker

Informations

• Publié par: biomed
• Publié le: 01 janvier 2011
• Nombre de lectures: 7
• Langue: English
• Poids de l'ouvrage: 2 Mo

Extrait

oCtOber 10, 2011

EUr J Med Res (2011) 16: 451-456

EuRoPEan JouRnal oF MEDIcal RESEaRcH

451

© I. HOLZàpfeL PUbLishers 2011

D o I nSulIn - lIKE G RowTH F acToR a SSocIaTED P RoTEInS Q ualIFy aS a T uMoR M aRKER ? R ESulTS oF a P RoSPEcTIvE S TuDy In 163 c ancER P aTIEnTS *

1 1 32 22 11 1 c. MàtUsChek , M. RUdOY , M. Peiper , P. a. Gerber , n. P. HOff, B. a. BUhreN , B. FLehmig, w. BUdàCh , 3 44 56 78 w. T. KNOefeL , H. BOjàr, H. B. PrisàCk, G. SteiNbàCh , v. ShUkLà , a. SChWàrZ , K. Kàmmers , 9 101 3 a. Erhàrdt , a. SCherer, E. BöLke , M. SChàUer

1 DepàrtmeNt Of RàdiàtiON TheràpY àNd RàdiOONCOLOgY, uNiVersitätskLiNikUm DüsseLdOrf, HeiNriCh HeiNe uNiVersität, DUesseLdOrf, GermàNY 2 DepàrtmeNt Of DermàtOLOgY, uNiVersitätskLiNikUm DüsseLdOrf, HeiNriCh HeiNe uNiVersität, DüsseLdOrf, GermàNY 3 DepàrtmeNt Of GeNeràL-, visCeràL-, àNd PediàtriC SUrgerY, uNiVersitätskLiNikUm DüsseLdOrf, HeiNriCh HeiNe uNiVersität, DüsseLdOrf, GermàNY 4 INstitUte Of MOLeCULàr MediCiNe, DüsseLdOrf, GermàNY 5 DepàrtmeNt Of cLiNiCàL chemistrY, uNiVersitY Of uLm, GermàNY 6 MethOdist HOspitàL, HOUstON, Texàs, uSa 7 DepàrtmeNt Of SUrgerY, HOspitàL BiberàCh, GermàNY 8 DepàrtmeNt Of StàtistiCs, uNiVersitY Of DOrtmUNd, GermàNY 9 DepàrtmeNt Of GàstrOeNterOLOgY, uNiVersitätskLiNikUm DüsseLdOrf, HeiNriCh HeiNe uNiVersität, DüsseLdOrf, GermàNY 10 INstitUte Of DiàgNOstiC àNd INterVeNtiONàL RàdiOLOgY, uNiVersitY HOspitàL, DüsseLdOrf, GermàNY 11 chiLdreNshOspitàL, uNiVersitY Of TübiNgeN, TübiNgeN, GermàNY

Abstract Objective:INsULiN-Like grOWth fàCtOr (IGF)-1, -2 àNd INsULiN Like grOWth fàCtOr biNdiNg prOteiNs (IGFBP) àre iNVOLVed iN the prOLiferàtiON àNd differeNtiàtiON Of CeLLs. It hàs NeVer beeN eVàLUàted, ifthe IGF-sYstem CàN serVe às à tUmOr màrker iN NeOpLàsms. Methods:IN OUr prOspeCtiVe stUdY 163 pàtieNts With COLOreCtàL CàNCer (22), prOstàte CàNCer (21), heàd àNd NeCk tUmOrs (17), LYmphOmàs (20), LUNg CàNCer (34) àNd Other eNtities (49) Were àNàLYsed fOr their IGF àNd IGFBP serUm LeVeLs àt the begiNNiNg àNd the eNd Of ràdiOtheràpY àNd COmpàred tO 13 heàLthY peOpLe. SUb- grOUps OfpàtieNts With LOCàL tUmOr diseàse VersUs metàstàtiC diseàse, primàrY àNd reCUrreNt theràpY àNd CUràtiVe VersUs pàLLiàtiVe theràpY Were COmpàred. Results:IGF-2 Were sigNifiCàNtLYThe serUm LeVeLs Of eLeVàted iN pàtieNts With prOstàte àNd COLOreCtàL CàN- Cer. HOWeVer, seNsitiVitY àNd speCifiCitY Were ONLY 70%. IGFBP-2 serUm LeVeLs Were eLeVàted iN pàtieNts With heàd àNd NeCk tUmOrs. agàiN seNsitiVitY àNd speCifiCitY Were ONLY 73%. a differeNCe betWeeN LOCàL diseàse àNd metàstàtiC diseàse COULd NOt be fOUNd. a differeNCe betWeeN IGF serUm LeVeLs befOre àNd àfter ràdiOtheràpY COULd NOt be deteCted. Conclusion:The IGF-sYstem CàNNOt serVe às à NeW tU- mOr màrker. The deteCted differeNCes àre VerY smàLL, seNsitiVitY àNd speCifiCitY àre tOO LOW. IGF meàsUre- meNt is NOt UsefUL fOr the eVàLUàtiON Ofthe sUCCess Of ràdiOtheràpY iN màLigNàNCies.

Key words:INsULiN-Like grOWth fàCtOr, tUmOr màrker, iNsULiN Like grOWth fàCtOr biNdiNg prOteiN;, prOgNOstiC fàCtOrs

* ThisWOrk is dediCàted tO Kim Speer.

I nTRoDucTIon

INsULiN-Like grOWth fàCtOrs (IGF)-1 (sOmàtOmediN c) àNd -2 (sOmàtOmediN a), IGF-reCeptOrs (IGF1R, IGF2R) àNd IGF-biNdiNg prOteiNs (IGFBP1-7) pàrtiC- ipàte iN the prOLiferàtiON, differeNtiàtiON àNd àpOptOsis dUriNg embrYOgeNesis àNd deVeLOpmeNt [1, 2]. There- fOre, IGF bLOOd LeVeLs depeNd ON pàtieNts’ àge àNd LiV- er fUNCtiON With àN effeCtiVe hàLf-Life frOm seVeN miN- Utes tO seVeràL hOUrs [3]. liNked tO the biNdiNg prO- teiN, the COmpLex CàNNOt LeàVe the bLOOd sYstem àNd hàLf-Life is àCCOrdiNgLY LONger [4, 5]. IN màLigNàNt tUmOrs, àUtOCriNe àNd pàràCriNe LOOps iN the IGF-sYstem CONtribUte tO the iNhibitiON Of àpOptOsis [6, 7]. a high CONCeNtràtiON Ofthis grOWth fàCtOr àNd its biNdiNg prOteiNs COULd be deteCted iN sàrCOmàs àNd màNY differeNt CàrCiNOmàs, sUCh às prOstàte, breàst, COLON àNd Other CàNCers [8-12]. IN these NeOpLàsms espeCiàLLY à high expressiON ràte àNd serUm LeVeL OfIGFBP-2 COULd be shOWN bY differeNt stUdies [13, 14]. IGFBP-2 seems tO pLàY à màjOr rOLe iN prOLiferàtiON àNd CeLL-àdhesiON. assUmàbLe, high LeVeLs Of àCidLàbiLe sUbUNits (alS) OfIGFBPs prOteCt frOm fàst tUmOr grOWth bY àN àssOCiàted higher àffiNitY [3]. The regULàtiNg effeCt Ofthe IGF-sYstem ON prOLiferà- tiON, àpOptOsis, CeLL-migràtiON àNd metàstàses COULd be demONstràted iN CeLL CULtUres àNd àLsO iN à tUmOr àNi- màL mOdeL [15, 16]. The VàriàtiON Ofthe IGF sYstem serUm LeVeLs, espe- CiàLLY OfIGFBP, ON tUmOr grOWth, metàstàses àNd UN- der àNtiprOLiferàtiVe theràpY hàs NOt sUffiCieNtLY beeN expLOred iN ViVO. a pOssibLe beNefit frOm IGF às à NeW tUmOr màrker hàs NeVer beeN àNàLYZed sO fàr. There- fOre We COmpàred serUm LeVeLs OfIGF-1 àNd -2 àNd IGFBP-2 àNd -3 OfpàtieNts With differeNt màLigNàNt diseàses With tUmOr stàgiNg àNd fUrther tUmOr prOgress àfter ChemOtheràpY, ràdiOtheràpY Or reseCtiON.