Diagnostic advancements for prostate cancer have so greatly increased early detections that hope abounds for improved patient outcomes. However, histopathology, which guides treatment, often subcategorizes aggressiveness insufficiently among moderately differentiated Gleason score (6 and 7) tumors (>70% of new cases). Here, we test the diagnostic capability of prostate metabolite profiles measured with intact tissue magnetic resonance spectroscopy and the sensitivity of local prostate metabolites in predicting prostate cancer status. Prostate tissue samples (n = 199) obtained from 82 prostate cancer patients after prostatectomy were analyzed with high-resolution magic angle spinning proton magnetic resonance spectroscopy, and afterwards with quantitative pathology. Metabolite profiles obtained from principal component analysis of magnetic resonance spectroscopy were correlated with pathologic quantitative findings by using linear regression analysis and evaluated against patient pathologic statuses by using ANOVA. Paired t tests show that tissue metabolite profiles can differentiate malignant from benign samples obtained from the same patient (P < 0.005) and correlate with patient serum prostate-specific antigen levels (P < 0.006). Furthermore, metabolite profiles obtained from histologically benign tissue samples of Gleason score 6 and 7 prostates can delineate a subset of less aggressive tumors (P < 0.008) and predict tumor perineural invasion within the subset (P < 0.03). These results indicate that magnetic resonance spectroscopy metabolite profiles of biopsy tissues may help direct treatment plans by assessing prostate cancer pathologic stage and aggressiveness, which at present can be histopathologically determined only after prostatectomy.
The 2004 World Health Organization classification of tumors defines epithelioid angiomyolipoma of kidney as a potentially malignant mesenchymal neoplasm with reported metastasis in approximately one-third of the cases. However, this conclusion was based primarily on individual case reports and small retrospective series. More recently reported larger series have shown varying results. We reviewed 437 consecutive renal angiomyolipomas with primary resection at three tertiary-care institutions with high nephrectomy volumes. Only tumors showing 480% epithelioid histology were included in this study. Tumors resected elsewhere and reviewed in consultation were not included. Twenty of these 437 (4.6%) were classified as epithelioid angiomyolipoma. The female to male ratio was 11:9, mean age 49.7 (range, 30-80) years, and mean tumor size 8.7 (range, 1-25) cm. Microscopic tumor necrosis was present in 10 (50%) tumors and mitotic activity (range, o1-5/10 high power fields) in 8 (40%); atypical mitoses were seen in only 1 (5%) tumor. Pleomorphic ganglion-like or multinucleated giant cells were seen in 18 (90%) tumors. With a mean follow-up of 82.5 (range, 1-356) months, seventeen patients were alive with no-evidence-of-disease at the time of last follow-up; two patients died of unrelated causes with no-evidence-of-disease, and one patient (5%) developed distant metastases. Our data, based on consecutively resected angiomyolipomas with long clinical follow-up, suggests that epithelioid angiomyolipomas constitute a small proportion of all angiomyolipomas, and the rate of aggressive behavior among epithelioid angiomyolipomas, even when showing morphologic features previously reported to portend aggressive clinical behavior, is very low.
The previously observed improvement in spectral resolution of tissue proton NMR with high-resolution magic angle spinning (HRMAS) was speculated to be due largely to freeze-thawing artifacts resulting from tissue storage. In this study, 12 human prostate samples were analyzed on a 14.1T spectrometer at 3°C, with HRMAS rates of 600 and 700 Hz. These samples were measured fresh and after they were frozen for 12-16 hr prior to thawing. The spectral linewidths measured from fresh and previously frozen samples were identical for all metabolites except citrate and acetate. The metabolite intensities of fresh and freeze-thawed samples depend on the quantification procedures used; however, in this experiment the differences of means were <30%. As expected, it was found that tissue storage impacts tissue quality for pathological analysis, and HRMAS conditions alone are not sufficiently destructive to impair pathological evaluation. Furthermore, although storage conditions affect absolute metabolite concentrations in NMR analysis, relative metabolite concentrations are less affected.
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