Skip to main content
Erschienen in: Medical Oncology 12/2014

01.12.2014 | Original Paper

MR imaging in hepatocellular carcinoma: correlations between MRI features and molecular marker VEGF

verfasst von: Zhaoqin Huang, Xiangjiao Meng, Jianjun Xiu, Xiuqin Xu, Lei Bi, Jie Zhang, Xue Han, Qingwei Liu

Erschienen in: Medical Oncology | Ausgabe 12/2014

Einloggen, um Zugang zu erhalten

Abstract

The aim of this paper was to investigate the correlations between magnetic resonance imaging (MRI) features and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC). Thirty-six patients with HCC included in this study underwent dynamic contrast-enhanced MR imaging and diffusion-weighted MR imaging. Signal intensity characteristics of HCCs were reviewed independently by two experienced radiologists. ADC maps were automatically computed. VEGF expression was evaluated by immunohistochemical staining. The grades of the VEGF expression were correlated inversely with the ADC values of the HCCs (r = −0.435, p = 0.008). Intensity heterogeneity correlated with VEGF expression (r = 0.571, p = 0.039). There is a significant correlation between the intensity of arterial enhancement and VEGF expression (r = −0.386, p = 0.02). However, no correlation was found between the VEGF grades and the intensity of enhancement in the hepatic portal venous and late phases, as well as equilibrium phase. Our results indicate that ADC value on DW-MRI, the signal intensity in arterial phase and intensity heterogeneity correlate with the degree of VEGF expression in hepatocellular carcinomas.
Literatur
2.
Zurück zum Zitat Nathan H, Schulick RD, Choti MA, Pawlik TM. Predictors of survival after resection of early hepatocellular carcinoma. Ann Surg. 2009;249:799–805.PubMedCrossRef Nathan H, Schulick RD, Choti MA, Pawlik TM. Predictors of survival after resection of early hepatocellular carcinoma. Ann Surg. 2009;249:799–805.PubMedCrossRef
3.
Zurück zum Zitat El-Serag HB, Marrero JA, Rudolph L, Reddy KR. Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology. 2008;134:1752–63.PubMedCrossRef El-Serag HB, Marrero JA, Rudolph L, Reddy KR. Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology. 2008;134:1752–63.PubMedCrossRef
4.
Zurück zum Zitat Llovet JM, Bruix J. Novel advancements in the management of hepatocellular carcinoma in 2008. J Hepatol. 2008;48(Suppl 1):S20–37.PubMedCrossRef Llovet JM, Bruix J. Novel advancements in the management of hepatocellular carcinoma in 2008. J Hepatol. 2008;48(Suppl 1):S20–37.PubMedCrossRef
5.
Zurück zum Zitat Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J. SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.PubMedCrossRef Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J. SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.PubMedCrossRef
6.
Zurück zum Zitat Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10:25–34.PubMedCrossRef Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10:25–34.PubMedCrossRef
7.
Zurück zum Zitat Brunocilla PR, Brunello F, Carucci P, Gaia S, Rolle E, Cantamessa A, Castiglione A, Ciccone G, Rizzetto M. Sorafenib in hepatocellular carcinoma: prospective study on adverse events, quality of life, and related feasibility under daily conditions. Med Oncol. 2013;30:345.PubMedCrossRef Brunocilla PR, Brunello F, Carucci P, Gaia S, Rolle E, Cantamessa A, Castiglione A, Ciccone G, Rizzetto M. Sorafenib in hepatocellular carcinoma: prospective study on adverse events, quality of life, and related feasibility under daily conditions. Med Oncol. 2013;30:345.PubMedCrossRef
8.
Zurück zum Zitat Horwitz E, Stein I, Andreozzi M, Nemeth J, Shoham A, Pappo O, Schweitzer N, Tornillo L, Kanarek N, Quagliata L, Zreik F, Porat RM, Finkelstein R, Reuter H, Koschny R, Ganten T, Mogler C, Shibolet O, Hess J, Breuhahn K, Grunewald M, Schirmacher P, Vogel A, Terracciano L, Angel P, Ben-Neriah Y, Pikarsky E. Human and mouse VEGFA-amplified hepatocellular carcinomas are highly sensitive to sorafenib treatment. Cancer Discov. 2014;4:730–43.PubMedCrossRef Horwitz E, Stein I, Andreozzi M, Nemeth J, Shoham A, Pappo O, Schweitzer N, Tornillo L, Kanarek N, Quagliata L, Zreik F, Porat RM, Finkelstein R, Reuter H, Koschny R, Ganten T, Mogler C, Shibolet O, Hess J, Breuhahn K, Grunewald M, Schirmacher P, Vogel A, Terracciano L, Angel P, Ben-Neriah Y, Pikarsky E. Human and mouse VEGFA-amplified hepatocellular carcinomas are highly sensitive to sorafenib treatment. Cancer Discov. 2014;4:730–43.PubMedCrossRef
10.
Zurück zum Zitat Heijmen L, Verstappen MC, Ter Voert EE, Punt CJ, Oyen WJ, de Geus-Oei LF, Hermans JJ, Heerschap A, van Laarhoven HW. Tumour response prediction by diffusion-weighted MR imaging: ready for clinical use? Crit Rev Oncol Hematol. 2012;83:194–207.PubMedCrossRef Heijmen L, Verstappen MC, Ter Voert EE, Punt CJ, Oyen WJ, de Geus-Oei LF, Hermans JJ, Heerschap A, van Laarhoven HW. Tumour response prediction by diffusion-weighted MR imaging: ready for clinical use? Crit Rev Oncol Hematol. 2012;83:194–207.PubMedCrossRef
11.
Zurück zum Zitat Koh DM, Collins DJ. Diffusion-weighted MRI in the body: applications and challenges in oncology. AJR Am J Roentgenol. 2007;188:1622–35.PubMedCrossRef Koh DM, Collins DJ. Diffusion-weighted MRI in the body: applications and challenges in oncology. AJR Am J Roentgenol. 2007;188:1622–35.PubMedCrossRef
12.
Zurück zum Zitat Cui Y, Zhang XP, Sun YS, Tang L, Shen L. Apparent diffusion coefficient: potential imaging biomarker for prediction and early detection of response to chemotherapy in hepatic meta-stases. Radiology. 2008;248:894–900.PubMedCrossRef Cui Y, Zhang XP, Sun YS, Tang L, Shen L. Apparent diffusion coefficient: potential imaging biomarker for prediction and early detection of response to chemotherapy in hepatic meta-stases. Radiology. 2008;248:894–900.PubMedCrossRef
13.
Zurück zum Zitat Dzik-Jurasz A, Domenig C, George M, Wolber J, Padhani A, Brown G, Doran S. Diffusion MRI for prediction of response of rectal cancer to chemoradiation. Lancet. 2002;360:307–8.PubMedCrossRef Dzik-Jurasz A, Domenig C, George M, Wolber J, Padhani A, Brown G, Doran S. Diffusion MRI for prediction of response of rectal cancer to chemoradiation. Lancet. 2002;360:307–8.PubMedCrossRef
14.
Zurück zum Zitat Mardor Y, Roth Y, Ochershvilli A, Spiegelmann R, Tichler T, Daniels D, Maier SE, Nissim O, Ram Z, Baram J, Orenstein A, Pfeffer R. Pretreatment prediction of brain tumors’ response to radiation therapy using high b-value diffusion-weighted MRI. Neoplasia. 2004;6:136–42.PubMedCentralPubMedCrossRef Mardor Y, Roth Y, Ochershvilli A, Spiegelmann R, Tichler T, Daniels D, Maier SE, Nissim O, Ram Z, Baram J, Orenstein A, Pfeffer R. Pretreatment prediction of brain tumors’ response to radiation therapy using high b-value diffusion-weighted MRI. Neoplasia. 2004;6:136–42.PubMedCentralPubMedCrossRef
15.
Zurück zum Zitat Smirniotopoulos JG, Murphy FM, Rushing EJ, Rees JH, Schroeder JW. Patterns of contrast enhancement in the brain and meninges. Radiographics. 2007;27:525–51.PubMedCrossRef Smirniotopoulos JG, Murphy FM, Rushing EJ, Rees JH, Schroeder JW. Patterns of contrast enhancement in the brain and meninges. Radiographics. 2007;27:525–51.PubMedCrossRef
16.
Zurück zum Zitat Hervey-Jumper SL, Garton HJ, Lau D, Altshuler D, Quint DJ, Robertson PL, Muraszko KM, Maher CO. Differences in vascular endothelial growth factor receptor expression and correlation with the degree of enhancement in medulloblastoma. J Neurosurg Pediatr. 2014;14:121–8.PubMedCrossRef Hervey-Jumper SL, Garton HJ, Lau D, Altshuler D, Quint DJ, Robertson PL, Muraszko KM, Maher CO. Differences in vascular endothelial growth factor receptor expression and correlation with the degree of enhancement in medulloblastoma. J Neurosurg Pediatr. 2014;14:121–8.PubMedCrossRef
17.
Zurück zum Zitat Yamaguchi R, Yano H, Iemura A, Ogasawara S, Haramaki M, Kojiro M. Expression of vascular endothelial growth factor in human hepatocellular carcinoma. Hepatology. 1998;28:68–77.PubMedCrossRef Yamaguchi R, Yano H, Iemura A, Ogasawara S, Haramaki M, Kojiro M. Expression of vascular endothelial growth factor in human hepatocellular carcinoma. Hepatology. 1998;28:68–77.PubMedCrossRef
18.
Zurück zum Zitat Gaudio E, Barbaro B, Alvaro D, Glaser S, Francis H, Ueno Y, Meininger CJ, Franchitto A, Onori P, Marzioni M, Taffetani S, Fava G, Stoica G, Venter J, Reichenbach R, De Morrow S, Summers R, Alpini G. Vascular endothelial growth factor stimulates rat cholangiocyte proliferation via an autocrine mechanism. Gastroenterology. 2006;130:1270–82.PubMedCrossRef Gaudio E, Barbaro B, Alvaro D, Glaser S, Francis H, Ueno Y, Meininger CJ, Franchitto A, Onori P, Marzioni M, Taffetani S, Fava G, Stoica G, Venter J, Reichenbach R, De Morrow S, Summers R, Alpini G. Vascular endothelial growth factor stimulates rat cholangiocyte proliferation via an autocrine mechanism. Gastroenterology. 2006;130:1270–82.PubMedCrossRef
19.
Zurück zum Zitat Gaudio E, Onori P, Franchitto A, Pannarale L, Alpini G, Alvaro D. Hepatic microcirculation and cholangiocyte physiopathology. Ital J Anat Embryol. 2005;110:71–5.PubMed Gaudio E, Onori P, Franchitto A, Pannarale L, Alpini G, Alvaro D. Hepatic microcirculation and cholangiocyte physiopathology. Ital J Anat Embryol. 2005;110:71–5.PubMed
20.
Zurück zum Zitat Aoyagi T, Shuto K, Okazumi S, Hayano K, Satoh A, Saitoh H, Shimada H, Nabeya Y, Kazama T, Matsubara H. Apparent diffusion coefficient correlation with oesophageal tumour stroma and angiogenesis. Eur Radiol. 2012;22:1172–7.PubMedCrossRef Aoyagi T, Shuto K, Okazumi S, Hayano K, Satoh A, Saitoh H, Shimada H, Nabeya Y, Kazama T, Matsubara H. Apparent diffusion coefficient correlation with oesophageal tumour stroma and angiogenesis. Eur Radiol. 2012;22:1172–7.PubMedCrossRef
21.
Zurück zum Zitat Heo SH, Jeong YY, Shin SS, Kim JW, Lim HS, Lee JH, Koh YS, Cho CK, Kang HK. Apparent diffusion coefficient value of diffusion-weighted imaging for hepatocellular carcinoma: correlation with the histologic differentiation and the expression of vascular endothelial growth factor. Korean J Radiol. 2010;11(3):295–303.PubMedCentralPubMedCrossRef Heo SH, Jeong YY, Shin SS, Kim JW, Lim HS, Lee JH, Koh YS, Cho CK, Kang HK. Apparent diffusion coefficient value of diffusion-weighted imaging for hepatocellular carcinoma: correlation with the histologic differentiation and the expression of vascular endothelial growth factor. Korean J Radiol. 2010;11(3):295–303.PubMedCentralPubMedCrossRef
22.
23.
24.
Zurück zum Zitat Casanovas O, Hicklin DJ, Bergers G, Hanahan D. Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell. 2005;8:299–309.PubMedCrossRef Casanovas O, Hicklin DJ, Bergers G, Hanahan D. Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell. 2005;8:299–309.PubMedCrossRef
25.
Zurück zum Zitat Leach MO, Brindle KM, Evelhoch JL, Griffiths JR, Horsman MR, Jackson A, Jayson GC, Judson IR, Knopp MV, Maxwell RJ, McIntyre D, Padhani AR, Price P, Rathbone R, Rustin GJ, Tofts PS, Tozer GM, Vennart W, Waterton JC, Williams SR, Workman P. Pharmacodynamic/Pharmacokinetic Technologies Advisory Committee, Drug Development Office, Cancer Research UK. The assessment of antiangiogenic and antivascular therapies in early-stage clinical trials using magnetic resonance imaging: issue and recommendations. Br J Cancer. 2005;92:1599–610.PubMedCentralPubMedCrossRef Leach MO, Brindle KM, Evelhoch JL, Griffiths JR, Horsman MR, Jackson A, Jayson GC, Judson IR, Knopp MV, Maxwell RJ, McIntyre D, Padhani AR, Price P, Rathbone R, Rustin GJ, Tofts PS, Tozer GM, Vennart W, Waterton JC, Williams SR, Workman P. Pharmacodynamic/Pharmacokinetic Technologies Advisory Committee, Drug Development Office, Cancer Research UK. The assessment of antiangiogenic and antivascular therapies in early-stage clinical trials using magnetic resonance imaging: issue and recommendations. Br J Cancer. 2005;92:1599–610.PubMedCentralPubMedCrossRef
26.
Zurück zum Zitat Kanematsu M, Osada S, Amaoka N, Goshima S, Kondo H, Kato H, Nishibori H, Yokoyama R, Hoshi H, Moriyama N. Expression of vascular endothelial growth factor in hepatocellular carcinoma and the surrounding liver and correlation with MRI findings. AJR Am J Roentgenol. 2005;184:832–41.PubMedCrossRef Kanematsu M, Osada S, Amaoka N, Goshima S, Kondo H, Kato H, Nishibori H, Yokoyama R, Hoshi H, Moriyama N. Expression of vascular endothelial growth factor in hepatocellular carcinoma and the surrounding liver and correlation with MRI findings. AJR Am J Roentgenol. 2005;184:832–41.PubMedCrossRef
27.
Zurück zum Zitat Mukhopadhyay D, Tsiokas L, Zhou XM, Foster D, Brugge JS, Sukhatme VP. Hypoxic induction of human vascular endothelial growth factor expression through c-Src activation. Nature. 1995;375:577–81.PubMedCrossRef Mukhopadhyay D, Tsiokas L, Zhou XM, Foster D, Brugge JS, Sukhatme VP. Hypoxic induction of human vascular endothelial growth factor expression through c-Src activation. Nature. 1995;375:577–81.PubMedCrossRef
28.
Zurück zum Zitat von Marschall Z, Cramer T, Höcker M, Finkenzeller G, Wiedenmann B, Rosewicz S. Dual mechanism of vascular endothelial growth factor upregulation by hypoxia in human hepatocellular carcinoma. Gut. 2001;48:87–96.CrossRef von Marschall Z, Cramer T, Höcker M, Finkenzeller G, Wiedenmann B, Rosewicz S. Dual mechanism of vascular endothelial growth factor upregulation by hypoxia in human hepatocellular carcinoma. Gut. 2001;48:87–96.CrossRef
29.
Zurück zum Zitat Salvaggio G, Furlan A, Agnello F, Cabibbo G, Marin D, Giannitrapani L, Genco C, Midiri M, Lagalla R, Brancatelli G. Hepatocellular carcinoma enhancement on contrast-enhanced CT and MR imaging: response assessment after treatment with sorafenib: preliminary results. Radiol Med. 2014;119:215–21.PubMedCrossRef Salvaggio G, Furlan A, Agnello F, Cabibbo G, Marin D, Giannitrapani L, Genco C, Midiri M, Lagalla R, Brancatelli G. Hepatocellular carcinoma enhancement on contrast-enhanced CT and MR imaging: response assessment after treatment with sorafenib: preliminary results. Radiol Med. 2014;119:215–21.PubMedCrossRef
Metadaten
Titel
MR imaging in hepatocellular carcinoma: correlations between MRI features and molecular marker VEGF
verfasst von
Zhaoqin Huang
Xiangjiao Meng
Jianjun Xiu
Xiuqin Xu
Lei Bi
Jie Zhang
Xue Han
Qingwei Liu
Publikationsdatum
01.12.2014
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 12/2014
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-014-0313-0

Weitere Artikel der Ausgabe 12/2014

Medical Oncology 12/2014 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.