Skip to main content
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 12/2006

01.12.2006 | Original article

Microvessel density and p53 in detecting cervical cancer by FDG PET in cases of suspected recurrence

verfasst von: Astrid A. M. van der Veldt, Lotty Hooft, Paul J. van Diest, Johannes Berkhof, Marrije R. Buist, Emile F. I. Comans, Otto S. Hoekstra, Carla F. M. Molthoff

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 12/2006

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Cervical cancer is the second most frequently diagnosed cancer in women worldwide. About one-third of patients experience recurrent disease. A better chance of survival might be achieved by the early detection of recurrent cervical cancer. [18F]fluoro-2-deoxy-D-glucose (FDG) PET could be a promising imaging modality for this purpose, given that FDG PET has high diagnostic efficacy. Ideally, pre-selection of patients should be performed before considering FDG PET. The purpose of this study was to investigate parameters of primary cervical cancer associated with recurrence as a basis for pre-selection of patients in whom FDG PET should be performed.

Methods

Thirty-eight cervical cancer patients, clinically suspected of having recurrent disease, underwent FDG PET. Tissue from primary tumours and nine histologically confirmed metastases was analysed for biomarkers possibly related to glucose metabolism and prognosis (vascular endothelial growth factor, CD31 for microvessel density, glucose transporter-1, hexokinases I, II and III, Ki67, p53, hypoxia-inducible factor 1α, and degree of infiltration by lymphocytes and macrophages).

Results

Based on clinical outcome, sensitivity and specificity of FDG PET were 96% and 100%, respectively. Cox regression revealed microvessel density and p53 (tumour suppressor protein) to be the two most important biomarkers for prediction of recurrence (hazard ratios 2.54 and 2.28, respectively). By combining these two biomarkers in a parallel test, sensitivity and specificity in predicting recurrence were 87% and 71%, respectively. Leave-one-out cross-validation demonstrated predictive validity of a model based on microvessel density and p53.

Conclusion

In this first study of its kind, we have demonstrated that microvessel density and p53 profiles could be important in pre-selecting cervical cancer patients for detection of recurrence by FDG PET.
Literatur
1.
Zurück zum Zitat Jemal A, Murray T, Samuels A, Ghafoor A, Ward E, Thun MJ. Cancer statistics, 2003. CA Cancer J Clin 2003;53:5–26PubMedCrossRef Jemal A, Murray T, Samuels A, Ghafoor A, Ward E, Thun MJ. Cancer statistics, 2003. CA Cancer J Clin 2003;53:5–26PubMedCrossRef
2.
Zurück zum Zitat Friedlander M. Guidelines for the treatment of recurrent and metastatic cervical cancer. Oncologist 2002;7:342–347PubMed Friedlander M. Guidelines for the treatment of recurrent and metastatic cervical cancer. Oncologist 2002;7:342–347PubMed
4.
Zurück zum Zitat Ijaz T, Eifel PJ, Burke T, Oswald MJ. Radiation therapy of pelvic recurrence after radical hysterectomy for cervical carcinoma. Gynecol Oncol 1998;70:241–246PubMedCrossRef Ijaz T, Eifel PJ, Burke T, Oswald MJ. Radiation therapy of pelvic recurrence after radical hysterectomy for cervical carcinoma. Gynecol Oncol 1998;70:241–246PubMedCrossRef
5.
Zurück zum Zitat Kecmanovic DM, Pavlov MJ, Kovacevic PA, Sepetkovski AV, Ceranic MS, Stamenkovic AB. Management of advanced pelvic cancer by exenteration. Eur J Surg Oncol 2003;29:743–746PubMedCrossRef Kecmanovic DM, Pavlov MJ, Kovacevic PA, Sepetkovski AV, Ceranic MS, Stamenkovic AB. Management of advanced pelvic cancer by exenteration. Eur J Surg Oncol 2003;29:743–746PubMedCrossRef
6.
Zurück zum Zitat Tangjitgamol S, Levenback CF, Beller U, Kavanagh JJ. Role of surgical resection for lung, liver, and central nervous system metastases in patients with gynecological cancer: a literature review. Int J Gynecol Cancer 2004;14:399–422PubMedCrossRef Tangjitgamol S, Levenback CF, Beller U, Kavanagh JJ. Role of surgical resection for lung, liver, and central nervous system metastases in patients with gynecological cancer: a literature review. Int J Gynecol Cancer 2004;14:399–422PubMedCrossRef
7.
Zurück zum Zitat Vermorken JB, Zanetta G, De Oliveira CF, van der Burg ME, Lacave AJ, Teodorovic I, et al. Randomized phase III trial of bleomycin, vindesine, mitomycin-C, and cisplatin (BEMP) versus cisplatin (P) in disseminated squamous-cell carcinoma of the uterine cervix: an EORTC Gynecological Cancer Cooperative Group study. Ann Oncol 2001;12:967–974PubMedCrossRef Vermorken JB, Zanetta G, De Oliveira CF, van der Burg ME, Lacave AJ, Teodorovic I, et al. Randomized phase III trial of bleomycin, vindesine, mitomycin-C, and cisplatin (BEMP) versus cisplatin (P) in disseminated squamous-cell carcinoma of the uterine cervix: an EORTC Gynecological Cancer Cooperative Group study. Ann Oncol 2001;12:967–974PubMedCrossRef
8.
Zurück zum Zitat Choi JI, Kim SH, Seong CK, Sim JS, Lee HJ, Do KH. Recurrent uterine cervical carcinoma: spectrum of imaging findings. Korean J Radiol 2000;1:198–207PubMed Choi JI, Kim SH, Seong CK, Sim JS, Lee HJ, Do KH. Recurrent uterine cervical carcinoma: spectrum of imaging findings. Korean J Radiol 2000;1:198–207PubMed
9.
Zurück zum Zitat Weber TM, Sostman HD, Spritzer CE, Ballard RL, Meyer GA, Clark-Pearson DL, et al. Cervical carcinoma: determination of recurrent tumor extent versus radiation changes with MR imaging. Radiology 1995;194:135–139PubMed Weber TM, Sostman HD, Spritzer CE, Ballard RL, Meyer GA, Clark-Pearson DL, et al. Cervical carcinoma: determination of recurrent tumor extent versus radiation changes with MR imaging. Radiology 1995;194:135–139PubMed
10.
Zurück zum Zitat Lai CH, Huang KG, See LC, Yen TC, Tsai CS, Chang TC, et al. Restaging of recurrent cervical carcinoma with dual-phase [18F]fluoro-2-deoxy-D-glucose positron emission tomography. Cancer 2004;100:544–552PubMedCrossRef Lai CH, Huang KG, See LC, Yen TC, Tsai CS, Chang TC, et al. Restaging of recurrent cervical carcinoma with dual-phase [18F]fluoro-2-deoxy-D-glucose positron emission tomography. Cancer 2004;100:544–552PubMedCrossRef
11.
Zurück zum Zitat Park DH, Kim KH, Park SY, Lee BH, Choi CW, Chin SY. Diagnosis of recurrent uterine cervical cancer: computed tomography versus positron emission tomography. Korean J Radiol 2000;1:51–55PubMedMATHCrossRef Park DH, Kim KH, Park SY, Lee BH, Choi CW, Chin SY. Diagnosis of recurrent uterine cervical cancer: computed tomography versus positron emission tomography. Korean J Radiol 2000;1:51–55PubMedMATHCrossRef
12.
Zurück zum Zitat Yen TC, See LC, Chang TC, Huang KG, Ng KK, Tang SG, et al. Defining the priority of using 18F-FDG PET for recurrent cervical cancer. J Nucl Med 2004;45:1632–1639PubMed Yen TC, See LC, Chang TC, Huang KG, Ng KK, Tang SG, et al. Defining the priority of using 18F-FDG PET for recurrent cervical cancer. J Nucl Med 2004;45:1632–1639PubMed
13.
Zurück zum Zitat Belhocine T, Thille A, Fridman V, Albert A, Seidel L, Nickers P, et al. Contribution of whole-body 18FDG PET imaging in the management of cervical cancer. Gynecol Oncol 2002;87:90–97PubMedCrossRef Belhocine T, Thille A, Fridman V, Albert A, Seidel L, Nickers P, et al. Contribution of whole-body 18FDG PET imaging in the management of cervical cancer. Gynecol Oncol 2002;87:90–97PubMedCrossRef
14.
Zurück zum Zitat Chang TC, Law KS, Hong JH, Lai CH, Ng KK, Hsueh S, et al. Positron emission tomography for unexplained elevation of serum squamous cell carcinoma antigen levels during follow-up for patients with cervical malignancies: a phase II study. Cancer 2004;101:164–171PubMedCrossRef Chang TC, Law KS, Hong JH, Lai CH, Ng KK, Hsueh S, et al. Positron emission tomography for unexplained elevation of serum squamous cell carcinoma antigen levels during follow-up for patients with cervical malignancies: a phase II study. Cancer 2004;101:164–171PubMedCrossRef
15.
Zurück zum Zitat Grigsby PW, Siegel BA, Dehdashti F, Mutch DG. Posttherapy surveillance monitoring of cervical cancer by FDG-PET. Int J Radiat Oncol Biol Phys 2003;55:907–913PubMedCrossRef Grigsby PW, Siegel BA, Dehdashti F, Mutch DG. Posttherapy surveillance monitoring of cervical cancer by FDG-PET. Int J Radiat Oncol Biol Phys 2003;55:907–913PubMedCrossRef
16.
Zurück zum Zitat Havrilesky LJ, Wong TZ, Secord AA, Berchuck A, Clarke-Pearson DL, Jones EL. The role of PET scanning in the detection of recurrent cervical cancer. Gynecol Oncol 2003;90:186–190PubMedCrossRef Havrilesky LJ, Wong TZ, Secord AA, Berchuck A, Clarke-Pearson DL, Jones EL. The role of PET scanning in the detection of recurrent cervical cancer. Gynecol Oncol 2003;90:186–190PubMedCrossRef
17.
Zurück zum Zitat Kerr IG, Manji MF, Powe J, Bakheet S, Al Suhaibani H, Subhi J. Positron emission tomography for the evaluation of metastases in patients with carcinoma of the cervix: a retrospective review. Gynecol Oncol 2001;81:477–480PubMedCrossRef Kerr IG, Manji MF, Powe J, Bakheet S, Al Suhaibani H, Subhi J. Positron emission tomography for the evaluation of metastases in patients with carcinoma of the cervix: a retrospective review. Gynecol Oncol 2001;81:477–480PubMedCrossRef
18.
Zurück zum Zitat Malyapa RS, Mutic S, Low DA, Zoberi I, Bosch WR, Laforest R, et al. Physiologic FDG-PET three-dimensional brachytherapy treatment planning for cervical cancer. Int J Radiat Oncol Biol Phys 2002;54:1140–1146PubMedCrossRef Malyapa RS, Mutic S, Low DA, Zoberi I, Bosch WR, Laforest R, et al. Physiologic FDG-PET three-dimensional brachytherapy treatment planning for cervical cancer. Int J Radiat Oncol Biol Phys 2002;54:1140–1146PubMedCrossRef
19.
Zurück zum Zitat Reinhardt MJ, Ehritt-Braun C, Vogelgesang D, Ihling C, Hogerle S, Mix M, et al. Metastatic lymph nodes in patients with cervical cancer: detection with MR imaging and FDG PET. Radiology 2001;218:776–782PubMed Reinhardt MJ, Ehritt-Braun C, Vogelgesang D, Ihling C, Hogerle S, Mix M, et al. Metastatic lymph nodes in patients with cervical cancer: detection with MR imaging and FDG PET. Radiology 2001;218:776–782PubMed
20.
Zurück zum Zitat Rose PG, Adler LP, Rodriguez M, Faulhaber PF, Abdul-Karim FW, Miraldi F. Positron emission tomography for evaluating para-aortic nodal metastasis in locally advanced cervical cancer before surgical staging: a surgicopathologic study. J Clin Oncol 1999;17:41–45PubMed Rose PG, Adler LP, Rodriguez M, Faulhaber PF, Abdul-Karim FW, Miraldi F. Positron emission tomography for evaluating para-aortic nodal metastasis in locally advanced cervical cancer before surgical staging: a surgicopathologic study. J Clin Oncol 1999;17:41–45PubMed
21.
Zurück zum Zitat Ryu SY, Kim MH, Choi SC, Choi CW, Lee KH. Detection of early recurrence with 18F-FDG PET in patients with cervical cancer. J Nucl Med 2003;44:347–352PubMed Ryu SY, Kim MH, Choi SC, Choi CW, Lee KH. Detection of early recurrence with 18F-FDG PET in patients with cervical cancer. J Nucl Med 2003;44:347–352PubMed
22.
Zurück zum Zitat Sun SS, Chen TC, Yen RF, Shen YY, Changlai SP, Kao A. Value of whole body 18F-fluoro-2-deoxyglucose positron emission tomography in the evaluation of recurrent cervical cancer. Anticancer Res 2001;21:2957–2961PubMed Sun SS, Chen TC, Yen RF, Shen YY, Changlai SP, Kao A. Value of whole body 18F-fluoro-2-deoxyglucose positron emission tomography in the evaluation of recurrent cervical cancer. Anticancer Res 2001;21:2957–2961PubMed
23.
Zurück zum Zitat Unger JB, Ivy JJ, Connor P, Charrier A, Ramaswamy MR, Ampil FL, et al. Detection of recurrent cervical cancer by whole-body FDG PET scan in asymptomatic and symptomatic women. Gynecol Oncol 2004;94:212–216PubMedCrossRef Unger JB, Ivy JJ, Connor P, Charrier A, Ramaswamy MR, Ampil FL, et al. Detection of recurrent cervical cancer by whole-body FDG PET scan in asymptomatic and symptomatic women. Gynecol Oncol 2004;94:212–216PubMedCrossRef
24.
Zurück zum Zitat Wong TZ, Jones EL, Coleman RE. Positron emission tomography with 2-deoxy-2-[18F]fluoro-D-glucose for evaluating local and distant disease in patients with cervical cancer. Mol Imaging Biol 2004;6:55–62PubMedCrossRef Wong TZ, Jones EL, Coleman RE. Positron emission tomography with 2-deoxy-2-[18F]fluoro-D-glucose for evaluating local and distant disease in patients with cervical cancer. Mol Imaging Biol 2004;6:55–62PubMedCrossRef
25.
Zurück zum Zitat Yen TC, See LC, Lai CH, Yah-Huei CW, Ng KK, Ma SY, et al. 18F-FDG uptake in squamous cell carcinoma of the cervix is correlated with glucose transporter 1 expression. J Nucl Med 2004;45:22–29PubMed Yen TC, See LC, Lai CH, Yah-Huei CW, Ng KK, Ma SY, et al. 18F-FDG uptake in squamous cell carcinoma of the cervix is correlated with glucose transporter 1 expression. J Nucl Med 2004;45:22–29PubMed
26.
Zurück zum Zitat Pauwels EK, Ribeiro MJ, Stoot JH, McCready VR, Bourguignon M, Maziere B. FDG accumulation and tumor biology. Nucl Med Biol 1998;25:317–322PubMedCrossRef Pauwels EK, Ribeiro MJ, Stoot JH, McCready VR, Bourguignon M, Maziere B. FDG accumulation and tumor biology. Nucl Med Biol 1998;25:317–322PubMedCrossRef
27.
Zurück zum Zitat Kung AL, Wang S, Klco JM, Kaelin WG, Livingston DM. Suppression of tumor growth through disruption of hypoxia-inducible transcription. Nat Med 2000;6:1335–1340PubMedCrossRef Kung AL, Wang S, Klco JM, Kaelin WG, Livingston DM. Suppression of tumor growth through disruption of hypoxia-inducible transcription. Nat Med 2000;6:1335–1340PubMedCrossRef
28.
Zurück zum Zitat Semenza G. Signal transduction to hypoxia-inducible factor 1. Biochem Pharmacol 2002;64:993–998PubMedCrossRef Semenza G. Signal transduction to hypoxia-inducible factor 1. Biochem Pharmacol 2002;64:993–998PubMedCrossRef
29.
Zurück zum Zitat van Diest PJ. No consent should be needed for using leftover body material for scientific purposes. BMJ 2002;325:648–651PubMedCrossRef van Diest PJ. No consent should be needed for using leftover body material for scientific purposes. BMJ 2002;325:648–651PubMedCrossRef
30.
Zurück zum Zitat Bos R, Der Hoeven JJ, van der Wall E, van der Groep P, van Diest PJ, Comans EF, et al. Biologic correlates of (18)fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography. J Clin Oncol 2002;20:379–387PubMedCrossRef Bos R, Der Hoeven JJ, van der Wall E, van der Groep P, van Diest PJ, Comans EF, et al. Biologic correlates of (18)fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography. J Clin Oncol 2002;20:379–387PubMedCrossRef
31.
Zurück zum Zitat Hooft L, van der Veldt AA, van Diest PJ, Hoekstra OS, Berkhof J, Teule GJ, et al. [18F]fluorodeoxyglucose uptake in recurrent thyroid cancer is related to hexokinase i expression in the primary tumor. J Clin Endocrinol Metab 2005;90:328–334PubMedCrossRef Hooft L, van der Veldt AA, van Diest PJ, Hoekstra OS, Berkhof J, Teule GJ, et al. [18F]fluorodeoxyglucose uptake in recurrent thyroid cancer is related to hexokinase i expression in the primary tumor. J Clin Endocrinol Metab 2005;90:328–334PubMedCrossRef
32.
Zurück zum Zitat Bos R, Zhong H, Hanrahan CF, Mommers EC, Semenza GL, Pinedo HM, et al. Levels of hypoxia-inducible factor-1 alpha during breast carcinogenesis. J Natl Cancer Inst 2001;93:309–314PubMedCrossRef Bos R, Zhong H, Hanrahan CF, Mommers EC, Semenza GL, Pinedo HM, et al. Levels of hypoxia-inducible factor-1 alpha during breast carcinogenesis. J Natl Cancer Inst 2001;93:309–314PubMedCrossRef
33.
Zurück zum Zitat Havrilesky LJ, Kulasingam SL, Matchar DB, Myers ER. FDG-PET for management of cervical and ovarian cancer. Gynecol Oncol 2005;97:183–191PubMedCrossRef Havrilesky LJ, Kulasingam SL, Matchar DB, Myers ER. FDG-PET for management of cervical and ovarian cancer. Gynecol Oncol 2005;97:183–191PubMedCrossRef
34.
Zurück zum Zitat von Schulthess GK. Positron emission tomography versus positron emission tomography/computed tomography: from “unclear” to “new-clear” medicine. Mol Imaging Biol 2004;6:183–187CrossRef von Schulthess GK. Positron emission tomography versus positron emission tomography/computed tomography: from “unclear” to “new-clear” medicine. Mol Imaging Biol 2004;6:183–187CrossRef
35.
Zurück zum Zitat Amit A, Beck D, Lowenstein L, Lavie O, Bar SR, Kedar Z, et al. The role of hybrid PET/CT in the evaluation of patients with cervical cancer. Gynecol Oncol 2006;100:65–69PubMedCrossRef Amit A, Beck D, Lowenstein L, Lavie O, Bar SR, Kedar Z, et al. The role of hybrid PET/CT in the evaluation of patients with cervical cancer. Gynecol Oncol 2006;100:65–69PubMedCrossRef
36.
Zurück zum Zitat Tohma T, Okazumi S, Makino H, Cho A, Mochiduki R, Shuto K, et al. Relationship between glucose transporter, hexokinase and FDG-PET in esophageal cancer. Hepatogastroenterology 2005;52:486–490PubMed Tohma T, Okazumi S, Makino H, Cho A, Mochiduki R, Shuto K, et al. Relationship between glucose transporter, hexokinase and FDG-PET in esophageal cancer. Hepatogastroenterology 2005;52:486–490PubMed
37.
Zurück zum Zitat Oka K, Suzuki Y, Nakano T. Expression of p27 and p53 in cervical squamous cell carcinoma patients treated with radiotherapy alone: radiotherapeutic effect and prognosis. Cancer 2000;88:2766–2773PubMedCrossRef Oka K, Suzuki Y, Nakano T. Expression of p27 and p53 in cervical squamous cell carcinoma patients treated with radiotherapy alone: radiotherapeutic effect and prognosis. Cancer 2000;88:2766–2773PubMedCrossRef
38.
Zurück zum Zitat Tjalma W, Van Marck E, Weyler J, Dirix L, Van Daele A, Goovaerts G, et al. Quantification and prognostic relevance of angiogenic parameters in invasive cervical cancer. Br J Cancer 1998;78:170–174PubMedCrossRef Tjalma W, Van Marck E, Weyler J, Dirix L, Van Daele A, Goovaerts G, et al. Quantification and prognostic relevance of angiogenic parameters in invasive cervical cancer. Br J Cancer 1998;78:170–174PubMedCrossRef
39.
Zurück zum Zitat Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 1990;63:1129–1136PubMedCrossRef Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 1990;63:1129–1136PubMedCrossRef
40.
Zurück zum Zitat Brenna SM, Zeferino LC, Pinto GA, Souza RA, Andrade LA, Vassalo J, et al. P53 expression as a predictor of recurrence in cervical squamous cell carcinoma. Int J Gynecol Cancer 2002;12:299–303PubMedCrossRef Brenna SM, Zeferino LC, Pinto GA, Souza RA, Andrade LA, Vassalo J, et al. P53 expression as a predictor of recurrence in cervical squamous cell carcinoma. Int J Gynecol Cancer 2002;12:299–303PubMedCrossRef
41.
Zurück zum Zitat Davidson B, Goldberg I, Gotlieb WH, Lerner-Geva L, Ben Baruch G, Agulansky L, et al. Macrophage infiltration and angiogenesis in cervical squamous cell carcinoma—clinicopathologic correlation. Acta Obstet Gynecol Scand 1999;78:240–244PubMedCrossRef Davidson B, Goldberg I, Gotlieb WH, Lerner-Geva L, Ben Baruch G, Agulansky L, et al. Macrophage infiltration and angiogenesis in cervical squamous cell carcinoma—clinicopathologic correlation. Acta Obstet Gynecol Scand 1999;78:240–244PubMedCrossRef
42.
Zurück zum Zitat Tjalma WA, Weyler JJ, Bogers JJ, Pollefliet C, Baay M, Goovaerts GC, et al. The importance of biological factors (bcl-2, bax, p53, PCNA, MI, HPV and angiogenesis) in invasive cervical cancer. Eur J Obstet Gynecol Reprod Biol 2001;97:223–230PubMedCrossRef Tjalma WA, Weyler JJ, Bogers JJ, Pollefliet C, Baay M, Goovaerts GC, et al. The importance of biological factors (bcl-2, bax, p53, PCNA, MI, HPV and angiogenesis) in invasive cervical cancer. Eur J Obstet Gynecol Reprod Biol 2001;97:223–230PubMedCrossRef
Metadaten
Titel
Microvessel density and p53 in detecting cervical cancer by FDG PET in cases of suspected recurrence
verfasst von
Astrid A. M. van der Veldt
Lotty Hooft
Paul J. van Diest
Johannes Berkhof
Marrije R. Buist
Emile F. I. Comans
Otto S. Hoekstra
Carla F. M. Molthoff
Publikationsdatum
01.12.2006
Verlag
Springer-Verlag
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 12/2006
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-006-0108-4

Weitere Artikel der Ausgabe 12/2006

European Journal of Nuclear Medicine and Molecular Imaging 12/2006 Zur Ausgabe