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Published in: Molecular Imaging and Biology 6/2017

01-12-2017 | Research Article

ADC Histogram Analysis of Cervical Cancer Aids Detecting Lymphatic Metastases—a Preliminary Study

Authors: Stefan Schob, Hans Jonas Meyer, Nikolaos Pazaitis, Dominik Schramm, Kristina Bremicker, Marc Exner, Anne Kathrin Höhn, Nikita Garnov, Alexey Surov

Published in: Molecular Imaging and Biology | Issue 6/2017

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Abstract

Purpose

Apparent diffusion coefficient (ADC) histogram analysis has been used to some extent in cervical cancer (CC) to distinguish between low-grade and high-grade tumors. Although this differentiation is undoubtedly helpful, it would be even more crucial in the presurgical setting to determine whether a tumor already gained the potential to metastasize via the lymphatic system. So far, no studies investigated the potential of 3T ADC histogram analysis in CC to differentiate between nodal-positive and nodal-negative entities. Therefore, the principal aim of our study was to investigate the potential of 3T ADC histogram analysis to differentiate between CC with and without lymph node metastasis. The second aim was to elucidate possible differences in ADC histogram parameters between CC with limited vs. advanced tumor stages and well-differentiated vs. undifferentiated lesions. Finally, correlations of p53 expression and Ki-67 index with ADC parameters were analyzed.

Procedures

Eighteen female patients (mean age 55.4 years, range 32–79 years) with histopathologically confirmed cervical squamous cell carcinoma of the uterine cervix were prospectively enrolled. Tumor stages, tumor grading, status of metastatic dissemination, Ki67-index, and p53 expression were assessed in these patients. Diffusion weighted imaging (DWI) was obtained in a 3T scanner using the following b values: b0 and b1000 s/mm2.

Results

Group comparisons using Mann-Whitney U test revealed the following findings: nodal-positive CC had statistically significant lower ADC parameters (ADCmin, ADCmean, median ADC, Mode, p10, p25, p75, and p90) in comparison to nodal-negative CC (all p < 0.05). ADCentropy was significantly elevated (p = 0.046) in tumors with advanced T stages (T3/4) compared to tumors with limited T stage (T2). ADCmin values were different in a statistically significant manner comparing G1/G2 and G3 tumors (40.45 ± 18.63 vs. 65.0 ± 23.63 × 10–5 mm2 s−1, p = 0.035). Furthermore, Spearman Rho calculation identified an inverse correlation between ADCentropy and p53 expression (r = −0.472, p = 0.048).

Conclusion

The main finding of our study is the discriminability of nodal-positive from nodal-negative CC using ADC histogram analysis in 3T DWI. This information is crucial for the gynecological surgeon to identify the optimal treatment strategy for patients suffering from CC. Furthermore, ADCentropy was identified as a potential imaging biomarker for tumor heterogeneity and might be able to indicate further molecular changes like loss of p53 expression, which is associated with EMT and consequentially indicates a poor prognosis in CC. Finally, our study confirmed the findings of previous works, which indicated that histogram analysis of ADC maps can distinguish between low-grade and high-grade CC. In conclusion, it can be stated that ADC histogram analysis provides additional, prognostically important information on tumor biology in CC.
Literature
1.
3.
go back to reference Aoki Y, Sasaki M, Watanabe M et al (2000) High-risk group in node-positive patients with stage IB, IIA, and IIB cervical carcinoma after radical hysterectomy and postoperative pelvic irradiation. Gynecol Oncol 77:305–309CrossRefPubMed Aoki Y, Sasaki M, Watanabe M et al (2000) High-risk group in node-positive patients with stage IB, IIA, and IIB cervical carcinoma after radical hysterectomy and postoperative pelvic irradiation. Gynecol Oncol 77:305–309CrossRefPubMed
4.
go back to reference Sakuragi N (2007) Up-to-date management of lymph node metastasis and the role of tailored lymphadenectomy in cervical cancer. Int J Clin Oncol 12:165–175CrossRefPubMed Sakuragi N (2007) Up-to-date management of lymph node metastasis and the role of tailored lymphadenectomy in cervical cancer. Int J Clin Oncol 12:165–175CrossRefPubMed
6.
go back to reference Gong Y, Wang Q, Dong L et al (2016) Different imaging techniques for the detection of pelvic lymph nodes metastasis from gynecological malignancies: a systematic review and meta-analysis. Oncotarget. doi:10.18632/oncotarget.12959 Gong Y, Wang Q, Dong L et al (2016) Different imaging techniques for the detection of pelvic lymph nodes metastasis from gynecological malignancies: a systematic review and meta-analysis. Oncotarget. doi:10.​18632/​oncotarget.​12959
7.
go back to reference Choi HJ, Roh JW, Seo S-S et al (2006) Comparison of the accuracy of magnetic resonance imaging and positron emission tomography/computed tomography in the presurgical detection of lymph node metastases in patients with uterine cervical carcinoma. Cancer 106:914–922CrossRefPubMed Choi HJ, Roh JW, Seo S-S et al (2006) Comparison of the accuracy of magnetic resonance imaging and positron emission tomography/computed tomography in the presurgical detection of lymph node metastases in patients with uterine cervical carcinoma. Cancer 106:914–922CrossRefPubMed
9.
go back to reference Surov A, Ginat DT, Sanverdi E et al (2016) Use of diffusion weighted imaging in differentiating between malignant and benign meningiomas. A multicenter analysis. WNEU 88:598–602 Surov A, Ginat DT, Sanverdi E et al (2016) Use of diffusion weighted imaging in differentiating between malignant and benign meningiomas. A multicenter analysis. WNEU 88:598–602
10.
go back to reference Schob S, Surov A, Wienke A et al (2016b) Correlation between aquaporin 4 expression and different DWI parameters in grade I meningioma. Mol Imaging Biol 19:138–142CrossRef Schob S, Surov A, Wienke A et al (2016b) Correlation between aquaporin 4 expression and different DWI parameters in grade I meningioma. Mol Imaging Biol 19:138–142CrossRef
11.
go back to reference Partridge SC, Mullins CD, Kurland BF et al (2010) Apparent diffusion coefficient values for discriminating benign and malignant breast MRI lesions: effects of lesion type and size. AJR Am J Roentgenol 194:1664–1673CrossRefPubMed Partridge SC, Mullins CD, Kurland BF et al (2010) Apparent diffusion coefficient values for discriminating benign and malignant breast MRI lesions: effects of lesion type and size. AJR Am J Roentgenol 194:1664–1673CrossRefPubMed
12.
go back to reference Shi HF, Feng Q, Qiang JW et al (2013) Utility of diffusion-weighted imaging in differentiating malignant from benign thyroid nodules with magnetic resonance imaging and pathologic correlation. J Comput Assist Tomogr 37:505–510CrossRefPubMed Shi HF, Feng Q, Qiang JW et al (2013) Utility of diffusion-weighted imaging in differentiating malignant from benign thyroid nodules with magnetic resonance imaging and pathologic correlation. J Comput Assist Tomogr 37:505–510CrossRefPubMed
13.
go back to reference Schob S, Voigt P, Bure L et al (2016c) Diffusion-weighted imaging using a readout-segmented, Multishot EPI sequence at 3 T distinguishes between morphologically differentiated and undifferentiated subtypes of thyroid carcinoma—a preliminary study. TRANON 9:403–410 Schob S, Voigt P, Bure L et al (2016c) Diffusion-weighted imaging using a readout-segmented, Multishot EPI sequence at 3 T distinguishes between morphologically differentiated and undifferentiated subtypes of thyroid carcinoma—a preliminary study. TRANON 9:403–410
15.
go back to reference Guan Y, Li W, Jiang Z et al (2016) Whole-lesion apparent diffusion coefficient-based entropy-related parameters for characterizing cervical cancers. Acad Radiol 23:1559–1567CrossRefPubMed Guan Y, Li W, Jiang Z et al (2016) Whole-lesion apparent diffusion coefficient-based entropy-related parameters for characterizing cervical cancers. Acad Radiol 23:1559–1567CrossRefPubMed
16.
go back to reference Xue H, Ren C, Yang J et al (2014) Histogram analysis of apparent diffusion coefficient for the assessment of local aggressiveness of cervical cancer. Arch Gynecol Obstet 290:341–348CrossRefPubMed Xue H, Ren C, Yang J et al (2014) Histogram analysis of apparent diffusion coefficient for the assessment of local aggressiveness of cervical cancer. Arch Gynecol Obstet 290:341–348CrossRefPubMed
17.
go back to reference Heo SH, Shin SS, Kim JW et al (2013a) Pre-treatment diffusion-weighted MR imaging for predicting tumor recurrence in uterine cervical cancer treated with concurrent chemoradiation: value of histogram analysis of apparent diffusion coefficients. Korean J Radiol 14:616–610CrossRefPubMedPubMedCentral Heo SH, Shin SS, Kim JW et al (2013a) Pre-treatment diffusion-weighted MR imaging for predicting tumor recurrence in uterine cervical cancer treated with concurrent chemoradiation: value of histogram analysis of apparent diffusion coefficients. Korean J Radiol 14:616–610CrossRefPubMedPubMedCentral
18.
go back to reference Downey K, Riches SF, Morgan VA et al (2013a) Relationship between imaging biomarkers of stage I cervical cancer and poor-prognosis histologic features: quantitative histogram analysis of diffusion-weighted MR images. AJR Am J Roentgenol 200:314–320CrossRefPubMed Downey K, Riches SF, Morgan VA et al (2013a) Relationship between imaging biomarkers of stage I cervical cancer and poor-prognosis histologic features: quantitative histogram analysis of diffusion-weighted MR images. AJR Am J Roentgenol 200:314–320CrossRefPubMed
19.
go back to reference Downey K, Riches SF, Morgan VA et al (2013b) Relationship between imaging biomarkers of stage I cervical cancer and poor-prognosis histologic features: quantitative histogram analysis of diffusion-weighted MR images. Am J Roentgenol 200:314–320CrossRef Downey K, Riches SF, Morgan VA et al (2013b) Relationship between imaging biomarkers of stage I cervical cancer and poor-prognosis histologic features: quantitative histogram analysis of diffusion-weighted MR images. Am J Roentgenol 200:314–320CrossRef
20.
go back to reference Heo SH, Shin SS, Kim JW et al (2013b) Pre-treatment diffusion-weighted MR imaging for predicting tumor recurrence in uterine cervical cancer treated with concurrent chemoradiation: value of histogram analysis of apparent diffusion coefficients. Korean J Radiol 14:616–625CrossRefPubMedPubMedCentral Heo SH, Shin SS, Kim JW et al (2013b) Pre-treatment diffusion-weighted MR imaging for predicting tumor recurrence in uterine cervical cancer treated with concurrent chemoradiation: value of histogram analysis of apparent diffusion coefficients. Korean J Radiol 14:616–625CrossRefPubMedPubMedCentral
21.
go back to reference Surov A, Caysa H, Wienke A et al (2015) Correlation between different ADC fractions, cell count, Ki-67, total nucleic areas and average nucleic areas in meningothelial meningiomas. Anticancer Res 35:6841–6846PubMed Surov A, Caysa H, Wienke A et al (2015) Correlation between different ADC fractions, cell count, Ki-67, total nucleic areas and average nucleic areas in meningothelial meningiomas. Anticancer Res 35:6841–6846PubMed
23.
go back to reference Rojas-Puentes L, Cardona AF, Carranza H et al (2016) Epithelial-mesenchymal transition, proliferation, and angiogenesis in locally advanced cervical cancer treated with chemoradiotherapy. Cancer Med 5:1989–1999CrossRefPubMedPubMedCentral Rojas-Puentes L, Cardona AF, Carranza H et al (2016) Epithelial-mesenchymal transition, proliferation, and angiogenesis in locally advanced cervical cancer treated with chemoradiotherapy. Cancer Med 5:1989–1999CrossRefPubMedPubMedCentral
24.
go back to reference Chen Y-W, Pan H-B, Tseng H-H et al (2013a) Differentiated epithelial- and mesenchymal-like phenotypes in subcutaneous mouse xenografts using diffusion weighted-magnetic resonance imaging. Int J Mol Sci 14:21943–21959CrossRefPubMedPubMedCentral Chen Y-W, Pan H-B, Tseng H-H et al (2013a) Differentiated epithelial- and mesenchymal-like phenotypes in subcutaneous mouse xenografts using diffusion weighted-magnetic resonance imaging. Int J Mol Sci 14:21943–21959CrossRefPubMedPubMedCentral
25.
go back to reference Rosenkrantz AB (2013) Histogram-based apparent diffusion coefficient analysis: an emerging tool for cervical cancer characterization? AJR Am J Roentgenol 200:311–313CrossRefPubMed Rosenkrantz AB (2013) Histogram-based apparent diffusion coefficient analysis: an emerging tool for cervical cancer characterization? AJR Am J Roentgenol 200:311–313CrossRefPubMed
26.
27.
go back to reference Chang C-J, Chao C-H, Xia W et al (2011) p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs. Nat Cell Biol 13:317–323CrossRefPubMedPubMedCentral Chang C-J, Chao C-H, Xia W et al (2011) p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs. Nat Cell Biol 13:317–323CrossRefPubMedPubMedCentral
28.
go back to reference Kim T, Veronese A, Pichiorri F et al (2011) p53 regulates epithelial-mesenchymal transition through microRNAs targeting ZEB1 and ZEB2. J Exp Med 208:875–883CrossRefPubMedPubMedCentral Kim T, Veronese A, Pichiorri F et al (2011) p53 regulates epithelial-mesenchymal transition through microRNAs targeting ZEB1 and ZEB2. J Exp Med 208:875–883CrossRefPubMedPubMedCentral
Metadata
Title
ADC Histogram Analysis of Cervical Cancer Aids Detecting Lymphatic Metastases—a Preliminary Study
Authors
Stefan Schob
Hans Jonas Meyer
Nikolaos Pazaitis
Dominik Schramm
Kristina Bremicker
Marc Exner
Anne Kathrin Höhn
Nikita Garnov
Alexey Surov
Publication date
01-12-2017
Publisher
Springer US
Published in
Molecular Imaging and Biology / Issue 6/2017
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-017-1073-y

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