Assessment of histopathological features of needle biopsy in recurrent prostate cancer following salvage high-intensity focused ultrasound.

INTRODUCTION: Local recurrence of prostate cancer (PCa) following radiotherapy may be treated with curative intent using salvage high-intensity focused ultrasound (s-HIFU). The interpretation of needle core biopsy specimens following s-HIFU is a daunting task, even for experienced pathologists. We describe various histopathological features encountered in biopsy specimens following whole-gland s-HIFU in one of the largest descriptive studies to date. METHODS: Fifty-five patients with biopsy-proven localized radio-recurrent PCa underwent s-HIFU and transrectal ultrasound (TRUS)-guided prostatic needle biopsies at 180 days post-treatment. All biopsies were reviewed by two genitourinary pathologists. RESULTS: PCa was detected in 11 (24%) biopsies. Radiation therapy-associated changes were identified in all cases. Additional findings included extensive coagulative stromal necrosis (100%), smudgy chromatin of cancer nuclei (82%), and markedly enlarged bizarre nuclei in the residual cancer (55%). Gleason grade assignment was possible in 10 (91%) of these biopsies and concordance of Gleason grading between pre- and post-therapy specimens was observed in six (60%) cases. CONCLUSIONS: The histological interpretation of needle biopsies following salvage HIFU is challenging and requires an understanding of the histopathological changes associated with this procedure in both tumoural and non-tumoural prostatic tissue. Accurate interpretation of the morphological changes following s-HIFU is instrumental for optimization of clinical decision-making and treatment planning in recurrent PCa.

Integrin-free tetraspanin CD151 can inhibit tumor cell motility upon clustering and is a clinical indicator of prostate cancer progression.

Normal physiology relies on the organization of transmembrane proteins by molecular scaffolds, such as tetraspanins. Oncogenesis frequently involves changes in their organization or expression. The tetraspanin CD151 is thought to contribute to cancer progression through direct interaction with the laminin-binding integrins α3ß1 and α6ß1. However, this interaction cannot explain the ability of CD151 to control migration in the absence of these integrins or on non-laminin substrates. We demonstrate that CD151 can regulate tumor cell migration without direct integrin binding and that integrin-free CD151 (CD151(free)) correlates clinically with tumor progression and metastasis. Clustering CD151(free) through its integrin-binding domain promotes accumulation in areas of cell-cell contact, leading to enhanced adhesion and inhibition of tumor cell motility in vitro and in vivo. CD151(free) clustering is a strong regulator of motility even in the absence of α3 expression but requires PKCα, suggesting that CD151 can control migration independent of its integrin associations. The histologic detection of CD151(free) in prostate cancer correlates with poor patient outcome. When CD151(free) is present, patients are more likely to recur after radical prostatectomy and progression to metastatic disease is accelerated. Multivariable analysis identifies CD151(free) as an independent predictor of survival. Moreover, the detection of CD151(free) can stratify survival among patients with elevated prostate-specific antigen levels. Cumulatively, these studies demonstrate that a subpopulation of CD151 exists on the surface of tumor cells that can regulate migration independent of its integrin partner. The clinical correlation of CD151(free) with prostate cancer progression suggests that it may contribute to the disease and predict cancer progression.

Increased risk of death from iron overload among 422 treated probands with HFE hemochromatosis and serum levels of ferritin greater than 1000 µg/L at diagnosis.

BACKGROUND & AIMS: We investigated the risk of death from iron overload among treated hemochromatosis probands who were homozygous for HFE C282Y and had serum levels of ferritin greater than 1000 µg/L at diagnosis. METHODS: We compared serum levels of ferritin at diagnosis and other conditions with the rate of iron overload-associated death using data from 2 cohorts of probands with hemochromatosis who were homozygous for HFE C282Y (an Alabama cohort, n = 294, 63.9% men and an Ontario cohort, n = 128, 68.8% men). We defined iron overload-associated causes of death as cirrhosis (including hepatic failure and primary liver cancer) caused by iron deposition and cardiomyopathy caused by myocardial siderosis. All probands received phlebotomy and other appropriate therapy. RESULTS: The mean survival times after diagnosis were 13.2 ± 7.3 y and 12.5 ± 8.3 y in Alabama and Ontario probands, respectively. Serum levels of ferritin greater than 1000 µg/L at diagnosis were observed in 30.1% and 47.7% of Alabama and Ontario probands, respectively. In logistic regressions of serum ferritin greater than 1000 µg/L, there were significant positive associations with male sex and cirrhosis in Alabama probands and with age, male sex, increased levels of alanine and aspartate aminotransferases, and cirrhosis in Ontario probands. Of probands with serum levels of ferritin greater than 1000 µg/L at diagnosis, 17.9% of those from Alabama and 14.8% of those from Ontario died of iron overload. Among probands with serum levels of ferritin greater than 1000 µg/L, the relative risk of iron overload-associated death was 5.4 for the Alabama group (95% confidence interval [CI], 2.2-13.1; P = .0002) and 4.9 for the Ontario group (95% CI, 1.1-22.0; P = .0359). CONCLUSIONS: In hemochromatosis probands homozygous for HFE C282Y, serum levels of ferritin greater than 1000 µg/L at diagnosis were positively associated with male sex and cirrhosis. Even with treatment, the relative risk of death from iron overload was 5-fold greater in probands with serum levels of ferritin greater than 1000 µg/L.

Ghrelin receptor as a novel imaging target for prostatic neoplasms.

BACKGROUND: Ghrelin is a natural growth hormone secretagogue (GHS) that is co-expressed with its receptor GHSR in human prostate cancer (PCa) cells. Imaging probes that target receptors for ghrelin may delineate PCas from benign disease. The specificity of a novel ghrelin-imaging probe for PCa over normal tissue or benign disease was assessed. METHODS: A fluorescein-bearing ghrelin analogue was synthesized (fluorescein-ghrelin(1-18)), and its application for imaging was evaluated in a panel of PCa cell lines and human prostate tissue. Prostate core biopsy samples were collected from fresh surgery specimens of 13 patients undergoing radical prostatectomy. Ghrelin probe signal was detected and quantified in each sample using a hapten amplification technique and associated with pathological features. RESULTS: The ghrelin probe was taken up by GHSR-expressing LNCaP and PC-3 cells, and not in BPH cells that express low levels of GHSR. Binding was blocked by competition with excess unlabeled probe. The ghrelin probe signal was 4.7 times higher in PCa compared to benign hyperplasia tissue (P = 0.0027) and normal tissue (P = 0.0093). Furthermore, while the ghrelin probe signal was 1.9-fold higher in PIN compared to benign hyperplasia (P = 0.0022) and normal tissue (P = 0.0047), there was no significant difference in the signal of benign hyperplasia compared to normal tissue. CONCLUSION: The imaging probe fluorescein-ghrelin(1-18) is specific for PCa, and did not associate significantly with benign hyperplasia or normal prostate tissue. This data suggests that ghrelin analogues may be useful as molecular imaging probes for prostatic neoplasms in both localized and metastatic disease.

Primary mucinous cystadenocarcinoma of the pelvic retroperitoneum in a male.

Primary mucinous cystadenocarcinoma of the retroperitoneum is an extremely rare malignancy with only 2 male patients reported in the literature. We describe an unusual case presenting as a pelvic mass in a male with previous pan-proctocolectomy and end ileostomy for Crohn's disease and review the available literature.

Acute muscle weakness owing to severe hypokalaemia resulting from dietary insufficiency: case report.

Acute muscle weakness with severe hypokalaemia is not uncommon in adults but is rare in children. An 11-month-old girl presented with hypokalaemic paralysis following a 1-month insufficiency of dietary potassium.