Skip to main content

Advertisement

SpringerLink
Log in

Clear cell renal cell carcinoma: identifying PTEN expression on multiphasic MDCT

  • Published:
Abdominal Radiology Aims and scope Submit manuscript

Abstract

Purpose

To investigate whether multiphasic MDCT enhancement profiles can help to identify PTEN expression in clear cell renal cell carcinomas (ccRCCs). Lack of PTEN expression is associated with worsened overall survival, a more advanced Fuhrman grade, and a greater likelihood of lymph mode metastasis.

Methods

With IRB approval for this retrospective study, we derived a cohort of 103 histologically proven ccRCCs with preoperative 4-phase renal mass MDCT from 2001–2013. Following manual segmentation, a computer-assisted detection algorithm selected a 0.5-cm-diameter region of maximal attenuation within each lesion in each phase; a 0.5-cm-diameter region of interest was manually placed on uninvolved renal cortex in each phase. The relative attenuation of each lesion was calculated as [(Maximal lesion attenuation − cortex attenuation)/cortex attenuation] × 100. Absolute and relative attenuation in each phase were compared using t tests. The performance of multiphasic enhancement in identifying PTEN expression was assessed with logistic regression analysis.

Results

PTEN-positive and PTEN-negative ccRCCs both exhibited peak enhancement in the corticomedullary phase. Relative corticomedullary phase attenuation was significantly greater for PTEN-negative ccRCCs in comparison to PTEN-positive ccRCCs (33.7 vs. 9.5, p = 0.03). After controlling for lesion stage and size, relative corticomedullary phase attenuation had an accuracy of 84% (86/103), specificity of 100% (84/84), sensitivity of 11% (2/19), positive predictive value of 100% (2/2), and negative predictive value of 83% (84/101) in identifying PTEN expression.

Conclusion

Relative corticomedullary phase attenuation may help to identify PTEN expression in ccRCCs, if validated prospectively.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Gore ME, Larkin JM (2011) Challenges and opportunities for converting renal cell carcinoma into a chronic disease with targeted therapies. Br J Cancer 104(3):399–406. https://doi.org/10.1038/sj.bjc.6606084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Srigley JR, Delahunt B, Eble JN, et al. (2013) The international society of urological pathology (ISUP) vancouver classification of renal neoplasia. Am J Surg Pathol 37(10):1469–1489. https://doi.org/10.1097/PAS.0b013e318299f2d1

    Article  PubMed  Google Scholar 

  3. Kovacs G, Akhtar M, Beckwith BJ, et al. (1997) The Heidelberg classification of renal cell tumours. J Pathol 183(2):131–133.https://doi.org/10.1002/(sici)1096-9896(199710)183:22%3C131::aid-path931%3E3.0.co;2-g

    Article  CAS  PubMed  Google Scholar 

  4. Truong LD, Shen SS (2011) Immunohistochemical diagnosis of renal neoplasms. Arch Pathol Lab Med 135(1):92–109. https://doi.org/10.1043/2010-0478-rar.1

    Article  PubMed  Google Scholar 

  5. Cheville JC, Lohse CM, Zincke H, Weaver AL, Blute ML (2003) Comparisons of outcome and prognostic features among histologic subtypes of renal cell carcinoma. Am J Surg Pathol 27(5):612–624

    Article  Google Scholar 

  6. Hoffmann NE, Gillett MD, Cheville JC, et al. (2008) Differences in organ system of distant metastasis by renal cell carcinoma subtype. J Urol 179(2):474–477. https://doi.org/10.1016/j.juro.2007.09.036

    Article  PubMed  Google Scholar 

  7. Amin MB, Corless CL, Renshaw AA, et al. (1997) Papillary (chromophil) renal cell carcinoma: histomorphologic characteristics and evaluation of conventional pathologic prognostic parameters in 62 cases. Am J Surg Pathol 21(6):621–635

    Article  CAS  Google Scholar 

  8. Beck SD, Patel MI, Snyder ME, et al. (2004) Effect of papillary and chromophobe cell type on disease-free survival after nephrectomy for renal cell carcinoma. Ann Surg Oncol 11(1):71–77

    Article  Google Scholar 

  9. Moch H, Gasser T, Amin MB, et al. (2000) Prognostic utility of the recently recommended histologic classification and revised TNM staging system of renal cell carcinoma: a Swiss experience with 588 tumors. Cancer 89(3):604–614

    Article  CAS  Google Scholar 

  10. Young JR, Margolis D, Sauk S, et al. (2013) Clear cell renal cell carcinoma: discrimination from other renal cell carcinoma subtypes and oncocytoma at multiphasic multidetector CT. Radiology 267(2):444–453. https://doi.org/10.1148/radiol.13112617

    Article  PubMed  Google Scholar 

  11. Lee-Felker SA, Felker ER, Tan N, et al. (2014) Qualitative and quantitative MDCT features for differentiating clear cell renal cell carcinoma from other solid renal cortical masses. AJR 203(5):W516–W524. https://doi.org/10.2214/ajr.14.12460

    Article  PubMed  Google Scholar 

  12. Coy H, Young JR, Douek ML, et al. (2017) Quantitative computer-aided diagnostic algorithm for automated detection of peak lesion attenuation in differentiating clear cell from papillary and chromophobe renal cell carcinoma, oncocytoma, and fat-poor angiomyolipoma on multiphasic multidetector computed tomography. Abdom Radiol (New York) 42(7):1919–1928. https://doi.org/10.1007/s00261-017-1095-6

    Article  Google Scholar 

  13. Zhang J, Lefkowitz RA, Ishill NM, et al. (2007) Solid renal cortical tumors: differentiation with CT. Radiology 244(2):494–504. https://doi.org/10.1148/radiol.2442060927

    Article  PubMed  Google Scholar 

  14. Kim JK, Kim TK, Ahn HJ, et al. (2002) Differentiation of subtypes of renal cell carcinoma on helical CT scans. AJR 178(6):1499–1506. https://doi.org/10.2214/ajr.178.6.1781499

    Article  PubMed  Google Scholar 

  15. Sheir KZ, El-Azab M, Mosbah A, El-Baz M, Shaaban AA (2005) Differentiation of renal cell carcinoma subtypes by multislice computerized tomography. J Urol 174(2):451–455 ((discussion 455)). https://doi.org/10.1097/01.ju.0000165341.08396.a9

    Article  PubMed  Google Scholar 

  16. Jinzaki M, Tanimoto A, Mukai M, et al. (2000) Double-phase helical CT of small renal parenchymal neoplasms: correlation with pathologic findings and tumor angiogenesis. J Comput Assist Tomogr 24(6):835–842

    Article  CAS  Google Scholar 

  17. Ruppert-Kohlmayr AJ, Uggowitzer M, Meissnitzer T, Ruppert G (2004) Differentiation of renal clear cell carcinoma and renal papillary carcinoma using quantitative CT enhancement parameters. AJR 183(5):1387–1391. https://doi.org/10.2214/ajr.183.5.1831387

    Article  PubMed  Google Scholar 

  18. Zhu C, Wei J, Tian X, Li Y, Li X (2015) Prognostic role of PPAR-γ and PTEN in the renal cell carcinoma. Int J Clin Exp Pathol 8(10):12668–12677

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Rosenkrantz AB, Matza BW, Portnoy E, et al. (2014) Impact of size of region-of-interest on differentiation of renal cell carcinoma and renal cysts on multi-phase CT: preliminary findings. Eur J Radiol 83(2):239–244. https://doi.org/10.1016/j.ejrad.2013.10.020

    Article  PubMed  Google Scholar 

  20. Young JR, Coy H, Douek M, et al. (2017) Type 1 papillary renal cell carcinoma: differentiation from type 2 papillary RCC on multiphasic MDCT. Abdom Radiol (New York) 42(7):1911–1918. https://doi.org/10.1007/s00261-017-1091-x

    Article  Google Scholar 

  21. Young JR, Coy H, Douek M, et al. (2017) Clear cell renal cell carcinoma: identifying the gain of chromosome 12 on multiphasic MDCT. Abdom Radiol (New York) 42(1):236–241. https://doi.org/10.1007/s00261-016-0868-7

    Article  Google Scholar 

  22. Young JR, Coy H, Kim HJ, et al. (2017) Performance of relative enhancement on multiphasic MRI for the differentiation of clear cell renal cell carcinoma (RCC) from papillary and chromophobe RCC subtypes and oncocytoma. AJR 208(4):812–819. https://doi.org/10.2214/ajr.16.17152

    Article  PubMed  Google Scholar 

  23. Young JR, Margolis D, Sauk S, et al. (2014) Clear cell renal cell carcinoma: multiphasic MDCT enhancement can predict the loss of chromosome 8p. Abdom Imaging 39(3):543–549. https://doi.org/10.1007/s00261-014-0092-2

    Article  PubMed  Google Scholar 

  24. Young JR, Young JA, Margolis DJ, et al. (2016) Clear cell renal cell carcinoma: identifying the gain of chromosome 20 on multiphasic MDCT. Abdom Radiol (New York) 41(11):2175–2181. https://doi.org/10.1007/s00261-016-0813-9

    Article  Google Scholar 

  25. Young JR, Coy H, Douek M, et al. (2017) Clear cell renal cell carcinoma: identifying the loss of the Y chromosome on multiphasic MDCT. AJR 209(2):333–338. https://doi.org/10.2214/ajr.16.17010

    Article  PubMed  Google Scholar 

  26. Young JR, Coy H, Kim HJ, et al. (2018) Utility of multiphasic multidetector computed tomography in discriminating between clear cell renal cell carcinomas with high and low carbonic anhydrase-IX expression. Abdom Radiol (New York) . https://doi.org/10.1007/s00261-018-1546-8

    Article  Google Scholar 

  27. Westfall PH, Krishen A (2001) Optimally weighted, fixed sequence and gatekeeper multiple testing procedures. J Stat Plan Inference 99(1):25–40. https://doi.org/10.1016/S0378-3758(01)00077-5

    Article  Google Scholar 

  28. Rodriguez S, Huynh-Do U (2012) The role of PTEN in tumor angiogenesis. J Oncol 2012:11. https://doi.org/10.1155/2012/141236

    Article  Google Scholar 

  29. Liu L, Li Y, Liu S, et al. (2017) Downregulation of miR-193a-3p inhibits cell growth and migration in renal cell carcinoma by targeting PTEN. Tumour Biol 39(6):1010428317711951. https://doi.org/10.1177/1010428317711951

    Article  PubMed  Google Scholar 

  30. Guo H, German P, Bai S, et al. (2015) The PI3K/AKT pathway and renal cell carcinoma. J Genet Genom 42(7):343–353. https://doi.org/10.1016/j.jgg.2015.03.003

    Article  Google Scholar 

  31. Gerlinger M, Rowan AJ, Horswell S, et al. (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366(10):883–892. https://doi.org/10.1056/NEJMoa1113205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was funded by the Society of Abdominal Radiology Howard S. Stern Research Grant. We thank the UCLA Computer Vision and Imaging Biomarker (CVIB) group, including Dr. Jonathan Goldin, Dr. Matthew Brown, Moe Moe Ko, and War War Ko, for their assistance with this study.

Author information

Authors and Affiliations

  1. Department of Radiology, UC Davis School of Medicine, 4860 Y Street #3100, Sacramento, CA, 95817, USA

    Jonathan R. Young

  2. Department of Radiology, David Geffen School of Medicine at UCLA, Los Angeles, USA

    Heidi Coy, Hyun J. Kim, Michael Douek & Steven S. Raman

  3. Department of Pathology, David Geffen School of Medicine at UCLA, Los Angeles, USA

    Anthony Sisk

  4. Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, USA

    Allan J. Pantuck

Authors
  1. Jonathan R. Young
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Heidi Coy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hyun J. Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael Douek
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anthony Sisk
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Allan J. Pantuck
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Steven S. Raman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jonathan R. Young.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

The Institutional Review Board waived the requirement of informed consent for this study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Young, J.R., Coy, H., Kim, H.J. et al. Clear cell renal cell carcinoma: identifying PTEN expression on multiphasic MDCT. Abdom Radiol 43, 3410–3417 (2018). https://doi.org/10.1007/s00261-018-1672-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00261-018-1672-3

Keywords

Search

Navigation