Skip to main content

Advertisement

Log in

Histogram Analysis Parameters Derived from Conventional T1- and T2-Weighted Images Can Predict Different Histopathological Features Including Expression of Ki67, EGFR, VEGF, HIF-1α, and p53 and Cell Count in Head and Neck Squamous Cell Carcinoma

  • Research Article
  • Published:
Molecular Imaging and Biology Aims and scope Submit manuscript

Abstract

Purpose

To analyze associations between histogram analysis parameters derived from conventional magnetic resonance imaging (MRI) and different histopathological features in head and neck squamous cell carcinoma (HNSCC).

Procedures

Thirty-four patients with histologically proven primary HNSCC were prospectively acquired. Histogram analysis was derived from pre-contrast T1-weighted (T1w) and T2-weighted (T2w) images. In all cases, expression of HIF-1α, VEGF, EGFR, p53, Ki67, and p16 as well as tumor cell count was analyzed.

Results

In the overall sample, inverse correlation between entropy derived from T1w images and p53 expression (p = − 0.458, P = 0.01) was found. Furthermore, p10 derived from T1w images correlated with VEGF expression (p = 0.371, P = 0.04). In the p16-positive tumors, VEGF expression correlated with several parameters derived from T1w images: mean (p = 0.481, P = 0.032), p10 (p = 0.489, P = 0.029), p25 (p = 0.475, P = 0.034), median (p = 0.468, P = 0.037), and mode (p = 0.492, P = 0.028). Several T2w parameters were associated with p53 expression: mean (p = 0.569, P = 0.007), p25 (p = 0.508, P = 0.019), p75 (p = 0.479, P = 0.028), median (p = 0.555, P = 0.009), and mode (p = 0.468, P = 0.033). Kurtosis derived from T2w images correlated with cell count (p = 0.534, P = 0.013). In p16-negative carcinomas, T2w parameters correlated with p53 expression: max (p = 0.736, P = 0.015), p90 (p = 0.687, P = 0.028), and standard deviation (p = 0.760, P = 0.011). T2w p10 (p = − 0.709, P = 0.022) and T2w p25 (p = − 0.733, P = 0.016) correlated also with HIF-1α expression.

Conclusions

Multiple associations between histogram parameters derived from T1w and T2w images and clinically relevant histopathological features were found in HNSCC. Therefore, imaging parameters can be also used as surrogate markers for tumor cellularity, proliferation, and vascularization in HNSCC. The identified correlations differed significantly between p16-positive and p16-negative cancers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1.
Fig. 2.
Fig. 3.

Similar content being viewed by others

References

  1. Braakhuis BJ, Leemans CR, Visser O (2014) Incidence and survival trends of head and neck squamous cell carcinoma in the Netherlands between 1989 and 2011. Oral Oncol 50:670–675

    Article  PubMed  Google Scholar 

  2. Szyszko TA, Cook GJR (2018) PET/CT and PET/MRI in head and neck malignancy. Clin Radiol 73:60–69

    Article  CAS  PubMed  Google Scholar 

  3. Padhani AR, Liu G, Koh DM et al (2009) Diffusion-weighted magnetic resonance imaging as a cancer biomarker: consensus and recommendations. Neoplasia 11:102–125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. O'Connor JP, Aboagye EO, Adams JE et al (2017) Imaging biomarker roadmap for cancer studies. Nat Rev Clin Oncol 14:169–186

    Article  CAS  PubMed  Google Scholar 

  5. Surov A, Meyer HJ, Wienke A (2017) Correlation between apparent diffusion coefficient (ADC) and cellularity is different in several tumors: a meta-analysis. Oncotarget 8:59492–59499

    PubMed  PubMed Central  Google Scholar 

  6. Surov A, Meyer HJ, Wienke A (2017) Associations between apparent diffusion coefficient (ADC) and KI 67 in different tumors: a meta-analysis. Part 1: ADCmean. Oncotarget 8:75434–75444

    PubMed  PubMed Central  Google Scholar 

  7. Little RA, Barjat H, Hare JI, Jenner M, Watson Y, Cheung S, Holliday K, Zhang W, O’Connor JPB, Barry ST, Puri S, Parker GJM, Waterton JC (2018) Evaluation of dynamic contrast-enhanced MRI biomarkers for stratified cancer medicine: how do permeability and perfusion vary between human tumours? Magn Reson Imaging 46:98–105

    Article  PubMed  Google Scholar 

  8. Surov A, Meyer HJ, Gawlitza M, Höhn AK, Boehm A, Kahn T, Stumpp P (2017) Correlations between DCE MRI and histopathological parameters in head and neck squamous cell carcinoma. Transl Oncol 10:17–21

    Article  PubMed  Google Scholar 

  9. Surov A, Stumpp P, Meyer HJ et al (2016) Simultaneous (18)F-FDG-PET/MRI: associations between diffusion, glucose metabolism and histopathological parameters in patients with head and neck squamous cell carcinoma. Oral Oncol 58:14–20

    Article  CAS  PubMed  Google Scholar 

  10. Driessen JP, Caldas-Magalhaes J, Janssen LM, Pameijer FA, Kooij N, Terhaard CHJ, Grolman W, Philippens MEP (2014) Diffusion-weighted MR imaging in laryngeal and hypopharyngeal carcinoma: association between apparent diffusion coefficient and histologic findings. Radiology 272:456–463

    Article  PubMed  Google Scholar 

  11. Just N (2014) Improving tumour heterogeneity MRI assessment with histograms. Br J Cancer 111:2205–2213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Schob S, Meyer HJ, Pazaitis N, Schramm D, Bremicker K, Exner M, Höhn AK, Garnov N, Surov A (2017) ADC histogram analysis of cervical cancer aids detecting lymphatic metastases—a preliminary study. Mol Imaging Biol 19:953–962

    Article  PubMed  Google Scholar 

  13. Liu S, Zhang Y, Chen L et al (2017) Whole-lesion apparent diffusion coefficient histogram analysis: significance in T and N staging of gastric cancers. BMC Cancer 17:665

    Article  PubMed  PubMed Central  Google Scholar 

  14. Meyer HJ, Leifels L, Schob S et al (2018) Histogram analysis parameters identify multiple associations between DWI and DCE MRI in head and neck squamous cell carcinoma. Magn Reson Imaging 45:72–77

    Article  PubMed  Google Scholar 

  15. Meyer HJ, Schob S, Münch B, Frydrychowicz C, Garnov N, Quäschling U, Hoffmann KT, Surov A (2018) Histogram analysis of T1-weighted, T2-weighted, and postcontrast T1-weighted images in primary CNS lymphoma: correlations with histopathological findings—a preliminary study. Mol Imaging Biol 20:318–323

    Article  PubMed  Google Scholar 

  16. Meyer HJ, Schob S, Höhn AK, Surov A (2017) MRI texture analysis reflects histopathology parameters in thyroid cancer—a first preliminary study. Transl Oncol 10:911–916

    Article  PubMed  PubMed Central  Google Scholar 

  17. Wu X, Sikiö M, Pertovaara H, Järvenpää R, Eskola H, Dastidar P, Kellokumpu-Lehtinen PL (2016) Differentiation of diffuse large B-cell lymphoma from follicular lymphoma using texture analysis on conventional mr images at 3.0 tesla. Acad Radiol 23:696–703

    Article  PubMed  Google Scholar 

  18. Ko ES, Kim JH, Lim Y, Han BK, Cho EY, Nam SJ (2016) Assessment of invasive breast cancer heterogeneity using whole-tumor magnetic resonance imaging texture analysis: correlations with detailed pathological findings. Medicine (Baltimore) 95:e2453

    Article  Google Scholar 

  19. Fischer CA, Kampmann M, Zlobec I, Green E, Tornillo L, Lugli A, Wolfensberger M, Terracciano LM (2010) P16 expression in oropharyngeal cancer: its impact on staging and prognosis compared with the conventional clinical staging parameters. Ann Oncol 21:1961–1966

    Article  CAS  PubMed  Google Scholar 

  20. Swartz JE, Pothen AJ, Stegeman I, Willems SM, Grolman W (2015) Clinical implications of hypoxia biomarker expression in head and neck squamous cell carcinoma: a systematic review. Cancer Med 4:1101–1116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Solomon MC, Vidyasagar MS, Fernandes D, Guddattu V, Mathew M, Shergill AK, Carnelio S, Chandrashekar C (2016) The prognostic implication of the expression of EGFR, p53, cyclin D1, Bcl-2 and p16 in primary locally advanced oral squamous cell carcinoma cases: a tissue microarray study. Med Oncol 33:138

    Article  CAS  PubMed  Google Scholar 

  22. Rasmussen GB, Vogelius IR, Rasmussen JH, Schumaker L, Ioffe O, Cullen K, Fischer BM, Therkildsen MH, Specht L, Bentzen SM (2015) Immunohistochemical biomarkers and FDG uptake on PET/CT in head and neck squamous cell carcinoma. Acta Oncol 54:1408–1415

    Article  CAS  PubMed  Google Scholar 

  23. Grönroos TJ, Lehtiö K, Söderström KO, Kronqvist P, Laine J, Eskola O, Viljanen T, Grénman R, Solin O, Minn H (2014) Hypoxia, blood flow and metabolism in squamous-cell carcinoma of the head and neck: correlations between multiple immunohistochemical parameters and PET. BMC Cancer 14:876

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Troy JD, Weissfeld JL, Youk AO, Thomas S, Wang L, Grandis JR (2013) Expression of EGFR, VEGF, and NOTCH1 suggest differences in tumor angiogenesis in HPV-positive and HPV-negative head and neck squamous cell carcinoma. Head Neck Pathol 7:344–355

    Article  PubMed  PubMed Central  Google Scholar 

  25. Surov A, Meyer HJ, Winter K, Richter C, Hoehn AK (2018) Histogram analysis parameters of apparent diffusion coefficient reflect tumor cellularity and proliferation activity in head and neck squamous cell carcinoma. Oncotarget 9:23599–23607

    PubMed  PubMed Central  Google Scholar 

  26. Chang PD, Malone HR, Bowden SG et al (2017) A multiparametric model for mapping cellularity in glioblastoma using radiographically localized biopsies. AJNR Am J Neuroradiol 38:890–898

    Article  CAS  PubMed  Google Scholar 

  27. Holli-Helenius K, Salminen A, Rinta-Kiikka I, Koskivuo I, Brück N, Boström P, Parkkola R (2017) MRI texture analysis in differentiating luminal A and luminal B breast cancer molecular subtypes—a feasibility study. BMC Med Imaging 17:69

    Article  PubMed  PubMed Central  Google Scholar 

  28. Dang M, Lysack JT, Wu T, Matthews TW, Chandarana SP, Brockton NT, Bose P, Bansal G, Cheng H, Mitchell JR, Dort JC (2015) MRI texture analysis predicts p53 status in head and neck squamous cell carcinoma. AJNR Am J Neuroradiol 36:166–170

    Article  CAS  PubMed  Google Scholar 

  29. de Perrot T, Lenoir V, Domingo Ayllón M, Dulguerov N, Pusztaszeri M, Becker M (2017) Apparent diffusion coefficient histograms of human papillomavirus-positive and human papillomavirus-negative head and neck squamous cell carcinoma: assessment of tumor heterogeneity and comparison with histopathology. AJNR Am J Neuroradiol 38:2153–2160

    Article  PubMed  Google Scholar 

  30. Nasri E, Wiesen LB, Knapik JA, Fredenburg KM (2018) Eps8 expression is significantly lower in p16+ head and neck squamous cell carcinomas (HNSCCs) compared with p16- HNSCCs. Hum Pathol 72:45–51

    Article  CAS  PubMed  Google Scholar 

  31. Bossi P, Resteghini C, Paielli N, Licitra L, Pilotti S, Perrone F (2016) Prognostic and predictive value of EGFR in head and neck squamous cell carcinoma. Oncotarget 7(45):74362–74379

    Article  PubMed  PubMed Central  Google Scholar 

  32. Ma X, Huang J, Wu X, Li X, Zhang J, Xue L, Li P, Liu L (2014) Epidermal growth factor receptor could play a prognostic role to predict the outcome of nasopharyngeal carcinoma: a meta-analysis. Cancer Biomark 14:267–277

    Article  CAS  PubMed  Google Scholar 

  33. Tandon S, Tudur-Smith C, Riley RD, Boyd MT, Jones TM (2010) A systematic review of p53 as a prognostic factor of survival in squamous cell carcinoma of the four main anatomical subsites of the head and neck. Cancer Epidemiol Biomark Prev 19:574–587

    Article  CAS  Google Scholar 

  34. Zang J, Li C, Zhao LN, Shi M, Zhou YC, Wang JH, Li X (2013) Prognostic value of vascular endothelial growth factor in patients with head and neck cancer: a meta-analysis. Head Neck 35:1507–1514

    PubMed  Google Scholar 

  35. Gong L, Zhang W, Zhou J, Lu J, Xiong H, Shi X, Chen J (2013) Prognostic value of HIFs expression in head and neck cancer: a systematic review. PLoS One 8:e75094

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Conception and design: H.J. Meyer, A. Surov

Development of methodology: H.J. Meyer, L. Leifels, A.K. Höhn, A. Surov

Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): H.J. Meyer, L. Leifels, G. Hamerla, A.K. Höhn, A. Surov

Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): H.J. Meyer, L. Leifels, G. Hamerla, A.K. Höhn

Writing, review, and/or revision of the manuscript: H.J. Meyer, A. Surov

Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): G. Hamerla, A.K. Höhn

Study supervision: A. Surov

Corresponding author

Correspondence to Hans Jonas Meyer.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethics Approval and Consent to Participate

This study adhered to the principles of the Declaration of Helsinki II and was approved by the Institutional Review Board of the University of Leipzig (ethics committee of the University of Leipzig, study codes 180-2007, 201-10-12072010, and 341-15-05102015). Written informed consent was obtained from all the study participants.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Meyer, H.J., Leifels, L., Hamerla, G. et al. Histogram Analysis Parameters Derived from Conventional T1- and T2-Weighted Images Can Predict Different Histopathological Features Including Expression of Ki67, EGFR, VEGF, HIF-1α, and p53 and Cell Count in Head and Neck Squamous Cell Carcinoma. Mol Imaging Biol 21, 740–746 (2019). https://doi.org/10.1007/s11307-018-1283-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11307-018-1283-y

Key words

Navigation