The dystroglycan (DG) complex is a transmembrane glycoprotein that forms a continuous link from the extracellular matrix to the actin cytoskeleton. Deregulated expression of DG has been reported in a variety of human malignancies and related to tumor aggressiveness. In this study expression of the DG subunit was evaluated by immunostaining in a series of renal epithelial cancers and its relation with traditional prognostic indicators and with the clinical outcome of the patients was evaluated.aDG expression was undetectable in a significant fraction of tumors (54%). In renal cell carcinomas (RCC) loss of a-DG staining correlated with higher tumor grade (p = 0.02) but not with tumor stage nor tumor size. In clear cell RCC patients loss of aDG staining correlated with an increased risk of recurrence (p = 0.002 by log-rank test) and death (p = 0.004) also when patients with lower grade or stage tumors were analyzed separately. In a multivariate analysis loss of DG staining confirmed to be and independent predictor of shorter disease-free (p = 0.001; RR = 4.9) and overall (p = 0.009; RR = 4.9) survival stronger than tumor grade and size.These findings demonstrate that loss of aDG expression, which correspond to loss of a functional DG complex, is a frequent event in human renal tumorigenesis and is an independent predictor of early recurrence and death for patients with clear cell RCC.

Prenatal ultrasound and magnetic resonance imaging features in a fetus with Walker–Warburg syndrome A 27-year-old woman was referred for targeted ultrasound examination at 26 weeks’ gestation following sonographic detection of fetal ventriculomegaly and posterior fossa abnormality. She and the father were Macedonian, non-consanguineous, healthy and had two healthy daughters. A mid-trimester abnormality scan had not been performed. On ultrasound examination the fetal cerebral ventricles were found to be enlarged (atrial width, 14 mm), the cerebellar vermis was not depicted and the fourth ventricle communicated with the cisterna magna, which was not enlarged (Figure 1). A median anechoic structure was interposed between the lateral ventricles, suggestive of a vein of Galen aneurysmal malformation. However, this diagnosis was easily excluded because the structure showed no signal on color Doppler imaging. Two days later, magnetic resonance imaging (MRI) confirmed the sonographic findings. Moreover, it showed a kinked Z-shaped brainstem, with bifid pons and medulla oblongata (Figure 2), and the mantle was thin with a simplified gyral pattern. The association of lissencephaly with cerebellar and brainstem anomalies suggested the diagnosis of Walker–Warburg syndrome (WWS). WWS is a rare autosomal recessive disorder characterized by congenital muscle dystrophy (CMD) and complex brain and eye abnormalities1,2. Additional ultrasound and MRI examinations showed progressive enlargement of the cerebral ventricles, the median anechoic structure and the cisterna magna (Figure 1c). At 31 weeks, retinal nonattachment/ detachment and asymmetry of the eye globes were observed (Figure 3). At 41 weeks a male fetus was vaginally delivered, with a birth weight of 3400 g and head circumference of 37.5 cm. The neonate showed spontaneous respiratory activity, but was deeply hypotonic and required gavage nutrition for impaired swallowing. Postnatal MRI showed active hydrocephalus (necessitating ventriculoperitoneal shunt placement), the typical ‘cobblestone’ appearance of lissencephaly and abnormal cerebellar gyration (Figure 4). Muscular biopsy on day 15 showed severely increased variability of the diameter of muscle fibers and endomisial fibrosis together with immunohistochemical reduction of glycosylated alpha-dystroglycan2. Molecular analysis showed a homozygous mutation in the protein-Omannosyltransferase 1 (POMT1) gene (c.1611C>G, p.Ser537Arg), which has previously been detected in other cases of WWS3,4. The infant died at 6 months of age. In fetuses postnatally proven to be affected by WWS, the cerebral anomalies detected by prenatal sonography are usually non-specific5 and suggestive of WWS only in cases with a positive family history. When familial history is uninformative, only the association of cerebral or cerebellar with ocular anomalies can suggest the correct diagnosis6,7. In the current case, sonography showed ventriculomegaly and dysplastic cerebellum, and the diag...

Expression levels of p27kip1, a negative regulator of the G1 phase of the cell cycle, and 8‐hydroxydeoxyguanosine (8‐OHdG), a marker of oxidative DNA damage, were assessed by immunostaining in a series of renal cell carcinomas (RCCs) and their prognostic significance was evaluated. Expression of p27kip1 as well as of the α‐subunit of the dystroglycan (DG) complex, previously reported to be altered in RCC, was also evaluated by western blot analysis. Nuclear expression of p27kip1 was reduced in a significant fraction of tumors and low p27kip1 staining correlated with higher tumor grade (P < 0.01). Recurrence and death from clear cell RCCs were significantly more frequent in p27kip1‐low expressing tumors and Kaplan–Meier curves showed a significant separation between high vs low expressor groups for both disease‐free (P = 0.011) and overall (P = 0.002) survival. Low nuclear expression of p27kip1 as well as loss of α‐DG were confirmed to be independent prognostic parameters at a multivariate analysis and the simultaneous loss of both molecules defined a “high‐risk” group of patients with increased risk of recurrence (RR = 28.7; P = 0.01) and death (RR = 12.9; P = 0.03). No significant correlation with clinical or pathological parameters was found for 8‐OHdG staining. Western blot analyses suggested a post‐translational mechanism for the loss of α‐DG expression and demonstrated that cytoplasmic dislocation of the protein contributes to the loss of active nuclear p27kip1. Loss of nuclear p27kip1 is a frequent event in human RCCs and is a powerful predictor of poor outcome which, in combination with low DG expression, could help to identify high‐risk patients with clear cell RCC. (Cancer Sci 2010; 00: 000–000)

Gleason score has been identified as an important variable to predict disease extent and biologic behaviour of prostate cancer. However, the correlation between Gleason score of needle biopsy and surgical specimen is often poor. We studied 72 patients who underwent needle biopsy and radical prostatectomy to correlate Gleason score with PSA, clinical and pathological tumour stage. Only 47.2% of Gleason scores were identical in the biopsy and specimens, 37.5% were undergraded and 15.2% were overgraded. Correlations between clinical and pathological stage were identical in 30.5% of patients, 61.1% of patients were understaged and 8.3% overstaged. In conclusion, accuracy of clinical staging and grading of prostate cancer is low. Although the Gleason score on needle biopsy might be useful to predict the final stage and grade, correlation with surgical specimen is poor.

The authors describe a case of synchronous bilateral involvement of the testes in a 70-year-old patient seven years after the onset of an IgG k IIIA multiple myeloma. Ultrasonographic and postoperative immunohistochemical studies were performed. A complete review of the literature shows the rarity of testicular plasmacytoma. The present one is the second reported case of syncronous involvement of the testes.