Correlation of prostate tumor eccentricity and Gleason scoring from prostatectomy and multi-parametric-magnetic resonance imaging

Abstract

Background: Proliferating cancer cells interacting with their microenvironment affects a tumor's spatial shape. Elongation or roundness (eccentricity) of lung, skin, and breast cancers indicates the cancer's relative aggressiveness. Non-invasive determination of the prostate tumor's shape should provide meaningful input for prognostication and clinical management. There are currently few studies of prostate tumor shape, therefore this study examines the relationship between a prostate tumor's eccentricity, derived from spatially registered multi-parametric MRI and histology slides, and Gleason scores.

Methods: A total of 26 consecutive patients were enrolled in the study. Median patient age was 60 years (range, 49 to 75 years), median PSA was 5.8 ng/mL (range, 2.3 to 23.7 ng/mL, and median Gleason score was 7 (range, 6 to 9). Multi-parametric MRI (T1, T2, Diffusion, Dynamic Contrast Enhanced) were resampled, rescaled, translated, and stitched to form spatially registered multi-parametric cubes. Multi-parametric signatures that characterize prostate tumors were inserted into a target detection algorithm (Adaptive Cosine Estimator, ACE). Various detection thresholds were applied to discriminate tumor from normal tissue. Also, tumor shape was computed from the histology slides. Blobbing, labeling, and calculation of eccentricity using moments of inertia were applied to the multi-parametric MRI and histology slides. The eccentricity measurements were compared to the Gleason scores from 25 patients.

Results: From histology slides analysis: the correlation coefficient between the eccentricity for the largest blob and a weighted average eccentricity against the Gleason score ranged from -0.67 to -0.78 for all 18 patients whose tumor volume exceeded 1.0 cc. From multi-parametric MRI analysis: the correlation coefficient between the eccentricity for the largest blob for varying thresholds against the Gleason score ranged from -0.60 to -0.66 for all 25 patients showing contrast uptake in the Dynamic Contrast Enhancement (DCE) MRI.

Conclusions: Spherical shape prostate adenocarcinoma shows a propensity for higher Gleason score. This novel finding follows lung and breast adenocarcinomas but depart from other primary tumor types. Analysis of multi-parametric MRI can non-invasively determine the prostate tumor's morphology and add critical information for prognostication and disease management. Eccentricity of smaller tumors (<1.0 cc) from MP-MRI correlates well with Gleason score, unlike eccentricity measured using histology of wholemount prostatectomy.

Keywords: Tumor morphology; histology of wholemount prostatectomy; multi-parametric MRI; prostate cancer; supervised target detection.

Figure 1

Schematic showing the overall procedure for generating tumor eccentricity from blobs derived from histology of wholemount prostatectomy specimens (solid blue arrows) and Adaptive Cosine Estimator (ACE) processing applied to multi-parametric MRI (MP-MRI). (solid red arrows) Blob eccentricity compared to Gleason scoring from histology (striped arrows).

Figure 2

Schematic illustrating analysis of histology slices from wholemount prostatectomy. (A) shows a montage of 7 transverse slices of histology slides from a patient. A pathologist has marked the tumor. Each slice was stained with hematoxylin and eosin. The images were recorded with 1,200 dots per inch spatial resolution. The marked tumors are digitally traced. (B) displays the computed eccentricity and volume for the blobs denoted in (A).

Figure 3

Schematic illustrating analysis of Adaptive Cosine Estimator (ACE) processing of Multi-parametric MRI (MP-MRI). Vertical and horizontal axis shows position within hypercube in pixels. (A) shows a mosaic of stitched ACE slices. Yellow rectangular outline shows the region that is magnified for display in (B). The computed eccentricity and volume for the expanded region in (A) and is shown in (B).

Figure 4

A scatterplot of the eccentricity from the largest blob (labeled as Blob Volume Max) in all 18 patients with tumor sizes >1 cc taken from analyzing the histology from wholemount prostatectomy plotted against the Gleason score.

Figure 5

A scatterplot of the correlation coefficients resulting from fitting the eccentricity from the largest blob against the Gleason score derived from the pathologist’s analysis of the histology vs. Adaptive Cosine Estimator (ACE) thresholds.

Figure 6

A scatterplot of the eccentricity from the largest blob of Adaptive Cosine Estimator (ACE) Multi-parametric MRI (MP-MRI) for detection thresholds ranging from 0.35 to 0.45 in 25 patients against the Gleason score derived from the pathologist’s analysis of the histology. Fitting parameters and correlation coefficients for linear fits of the eccentricity against Gleason score are also shown.