Background parenchymal enhancement in preoperative breast MRI

We aimed to assess the influence of background parenchymal enhancement (BPE) on surgical planning performed using preoperative MRI for breast cancer evaluation. Between January 2009 and December 2010, 91 newly diagnosed breast cancer patients (mean age, 55.5 years; range, 30−88 years) who underwent preoperative bilateral breast MRI followed by planned breast conservation therapy were retrospectively enrolled. MRI was performed to assess the tumor extent in addition to mammography and breast ultrasonography. BPE in the contralateral normal breast MRI at the early dynamic phase was visually classified as follows: minimal (n=49), mild (n=27), moderate (n=7), and marked (n=8). The correlations between the BPE grade and age, menopausal status, index tumor size, changes in surgical management based on MRI results, positive predictive value (PPV) of MRI, and surgical margins were assessed. Patients in the strong BPE groups were significantly younger (p=0.002) and generally premenopausal (p<0.001). Surgical treatment was not changed in 67 cases (73.6%), while extended excision and mastectomy were performed in 12 cases (13.2%), each based on additional lesions on MRI. Six of 79 (7.6%) patients who underwent breast conservation therapy had tumor-positive resection margins. In cases where surgical management was changed, the PPV for MRI-detected foci was high in the minimal (91.7%) and mild groups (66.7%), and 0% in the moderate and marked groups (p=0.002). Strong BPE causes false-positive MRI findings and may lead to overly extensive surgery, whereas MRI may be beneficial in select patients with weak BPE

Phosphorylation-dependent Akt-Inversin interaction at the basal body of primary cilia

A primary cilium is a microtubule-based sensory organelle that plays an important role in human development and disease. However, regulation of Akt in cilia and its role in ciliary development has not been demonstrated. Using yeast two-hybrid screening, we demonstrate that Inversin (INVS) interacts with Akt. Mutation in the INVS gene causes nephronophthisis type II (NPHP2), an autosomal recessive chronic tubulointerstitial nephropathy. Co-immunoprecipitation assays show that Akt interacts with INVS via the C-terminus. In vitro kinase assays demonstrate that Akt phosphorylates INVS at amino acids 864-866 that are required not only for Akt interaction, but also for INVS dimerization. Co-localization of INVS and phosphorylated form of Akt at the basal body is augmented by PDGF-AA. Akt-null MEF cells as well as siRNA-mediated inhibition of Akt attenuated ciliary growth, which was reversed by Akt reintroduction. Mutant phosphodeador NPHP2-related truncated INVS, which lack Akt phosphorylation sites, suppress cell growth and exhibit distorted lumen formation and misalignment of spindle axis during cell division. Further studies will be required for elucidating functional interactions of Akt-INVS at the primary cilia for identifying the molecular mechanisms underlying NPHP2

Prediction of background parenchymal enhancement on breast MRI using mammography, ultrasonography, and diffusion-weighted imaging

This retrospective study assessed the effects of menopausal status and menstrual cycle on background parenchymal enhancement (BPE) of breast magnetic resonance imaging (MRI), and investigated whether the degree of BPE can be predicted by findings of mammography, ultrasonography (US), and diffusion-weighted MR imaging (DWI). There were 160 study patients (80 premenopausal, 80 postmenopausal). Degree of BPE was classified into minimal, mild, moderate, or marked. Mammographic density was classified into fatty, scattered, heterogeneously dense, and extremely dense. BP echotexture on US and BP intensity on DWI were visually classified as homogeneous or heterogeneous. Apparent diffusion coefficient (ADC) values of normal breast tissue were measured. Associations of the degree of BPE with menopausal status, menstrual cycle, or imaging features were evaluated by univariate and multivariate analyses. No significant correlation was found between mammographic density and BPE (p=0.085), whereas menopausal status (p=0.000), BP echotexture (p=0.000), and BP intensity on DWI (p= 0.000), and ADC values (p=0.000) showed significant correlations with BPE. Multivariate analysis showed that postmenopausal status was an independent predictor of minimal BPE (p=0.002, OR=3.743). In premenopausal women, there was no significant correlation between menstrual cycle and BPE, whereas BP echotexture was an independent predictor of whether BPE was less than mild or greater than moderate (p=0.001, OR=26.575). BPE on breast MRI is associated with menopausal status and the findings of US and DWI. Because premenopausal women with heterogeneous BP echotexture may be predicted to show moderate or marked BPE, scheduling of breast MRI should preferentially be adjusted to the menstrual cycle