IMAGING

Correlation of MR imaging and MR spectroscopic imaging findings with Ki-67, phospho-Akt, and androgen receptor expression in prostate cancer
Shukla-Dave A, Hricak H, Ishill NM, Moskowitz CS, Drobnjak M, Reuter VE, Zakian KL, Scardino PT, Cordon-Cardo C
Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Radiology. 2009; 250: 803-12

• Purpose: To retrospectively assess whether magnetic resonance (MR) imaging and MR spectroscopic imaging and selected molecular markers correlate with each other and with clinically insignificant and significant prostate cancer (PCa), as defined at surgical pathologic analysis.
• Materials and Methods: The institutional review board approved this HIPAA-compliant study and waived informed consent. Eighty-nine men (mean age, 63 years; range, 46-79 years) with biopsy-proved PCa underwent combined endorectal MR imaging and MR spectroscopic imaging before radical prostatectomy. Suspicion of clinically insignificant PCa was retrospectively and separately recorded for MR imaging and combined MR imaging and MR spectroscopic imaging by using a scale of 0-3. Clinically insignificant PCa was pathologically defined as organ-confined cancer of 0.5 cm(3) or less without poorly differentiated elements. Prostatectomy specimens underwent immunohistochemical analysis for three molecular markers: Ki-67, phospho-Akt (pAkt), and androgen receptor (AR). To examine differences in marker levels for clinically insignificant and significant cancer, a Wilcoxon rank sum test was used. To examine correlations between marker levels and MR imaging or combined MR imaging and MR spectroscopic imaging scores, the Spearman correlation was used.
• Results: Twenty-one (24%) patients had clinically insignificant and 68 (76%) had clinically significant PCa at surgical pathologic review. All markers were significantly correlated with MR imaging and combined MR imaging and MR spectroscopic imaging findings (all correlation coefficients > 0.5). In differentiating clinically insignificant from clinically significant PCa, areas under the receiver operating characteristic curves for Ki-67, AR, pAkt, MR imaging, and combined MR imaging and MR spectroscopic imaging were 0.75, 0.78, 0.80, 0.85, and 0.91, respectively.
• Conclusion: The use of pretreatment MR imaging or combined MR imaging and MR spectroscopic imaging and molecular marker analyses of biopsy samples could facilitate better treatment selection. Supplemental material: http://radiology.rsnajnls.org/cgi/content/full/250/3/803/DC1.
  
  
• Editorial Comment
  Insignificant prostate cancer is defined as cancer found on biopsy (T1c), with PSAD < 0.15 ng/mL, Gleason score 6 or lower, or no more than 2 cores with cancer or greater than 50% involvement of any core.As we know insignificant prostate cancer is better defined as low-volume, low-grade tumor since around 10 % of this lesions may present with extra-prostatic extension on radical prostatectomy (1). In this very interesting manuscript, the authors reported a frequency of 24% of patients with clinically insignificant prostate cancer at radical prostatectomy. Although with some controversy (2), the same group of authors has been shown recently that a nomogram that incorporates MRI and MRSI was more accurate than clinical nomograms (clinical stage, PSA level, biopsy data) in order to predict clinically insignificant prostate cancer (3).
  In a study of 89 men with biopsy-proven prostate cancer, the authors demonstrated that combined MRI and MRSI findings and three specific biologic markers that are important in proliferation, apoptosis, and cell survival (Ki-67, phospho-Akt, and androgen receptor AR values) correlated with each other and with clinically insignificant and significant prostate cancer defined at pathologic examination of prostatectomy specimens.
  We agree with the authors that if a prospective study confirms their results it may represent the beginning of a new era. An era of integration of pretreatment conventional and functional MR imaging of the prostate with histopathological and specific biologic markers analyses of biopsy specimens. In the near future, this integration probably will allow better treatment selection and thus better outcome for patients with prostate cancer.

References
1. Johnstone PA, Rossi PJ, Jani AB, Master V: ‘Insignificant’ prostate cancer on biopsy: pathologic results from subsequent radical prostatectomy. Prostate Cancer Prostatic Dis. 2007; 10: 237-41.
2. Cabrera AR, Coakley FV, Westphalen AC, Lu Y, Zhao S, Shinohara K, et al.: Prostate cancer: is inapparent tumor at endorectal MR and MR spectroscopic imaging a favorable prognostic finding in patients who select active surveillance? Radiology. 2008; 247: 444-50.
3. Shukla-Dave A, Hricak H, Kattan MW, Pucar D, Kuroiwa K, Chen HN, et al.: The utility of magnetic resonance imaging and spectroscopy for predicting insignificant prostate cancer: an initial analysis. BJU Int. 2007; 99: 786-93.

Dr. Adilson Prando
Chief, Department of Radiology and
Diagnostic Imaging, Vera Cruz Hospital
Campinas, São Paulo, Brazil
E-mail: adilson.prando@gmail.com