Faculty Bibliography

Background The presence of muscularis propria invasion by bladder cancer is a key factor in prognosis and treatment decisions, although may be missed by biopsy due to sampling error. MRI has shown potential for detection of muscle invasion but has not specifically been evaluated for this purpose in the setting of bladder cancer patients without evidence of muscle invasion on initial biopsy. Purpose To evaluate the role of MRI in detection of muscularis propria invasion by bladder cancer following a pathologic diagnosis of non-invasive tumor. Material and Methods This retrospective study included 23 patients who underwent pelvic MRI following a pathologic diagnosis of bladder cancer without muscularis propria invasion and in whom additional histologic evaluation was performed following MRI. Two radiologists in consensus reviewed T2-weighted images to identify those cases suspicious for muscle invasion on MRI. The radiologists identified whether cases suspicious for invasion demonstrated disruption of the T2-hypointense muscularis layer of the bladder wall, peri-vesical fat stranding, and peri-vesical soft tissue nodularity. Findings were compared with pathologic results obtained after MRI. Results Suspicion was raised for muscle invasion in eight of 23 cases, four of which exhibited invasion on follow-up pathology. No case without suspicion on MRI exhibited invasion on follow-up pathology. Therefore, sensitivity and specificity were 100% and 79%, respectively. Among individual findings, muscularis disruption on T2WI exhibited sensitivity of 100% and specificity of 79%, peri-vesical fat stranding exhibited sensitivity and specificity of 50% and 84%, and peri-vesical soft tissue nodularity exhibited sensitivity and specificity of 25% and 100%. Conclusion MRI demonstrated high sensitivity for detection of muscle invasion in cases of bladder cancer without invasion on initial histologic assessment. Muscularis disruption on T2WI appeared to exhibit a better combination of sensitivity and specificity than did peri-vesical changes.

In prostate cancer, the signals that drive cell proliferation change as tumors progress from castration-sensitive (androgen-dominant) to castration-resistant states. While the mechanisms underlying this change remain uncertain, characterization of common signaling components that regulate both stages of prostate cancer proliferation is important for developing effective treatment strategies. Here, we demonstrate that paxillin, a known cytoplasmic adaptor protein, regulates both androgen- and EGF-induced nuclear signaling. We show that androgen and EGF promoted MAPK-dependent phosphorylation of paxillin, resulting in nuclear translocation of paxillin. We found nuclear paxillin could then associate with androgen-stimulated androgen receptor (AR). This complex bound AR-sensitive promoters, retaining AR within the nucleus and regulating AR-mediated transcription. Nuclear paxillin also complexed with ERK and ELK1, mediating c-FOS and cyclin D1 expression; this was followed by proliferation. Thus, paxillin is a liaison between extranuclear MAPK signaling and nuclear transcription in response to androgens and growth factors, making it a potential regulator of both castration-sensitive and castration-resistant prostate cancer. Accordingly, paxillin was required for normal growth of human prostate cancer cell xenografts, and its expression was elevated in human prostate cancer tissue microarrays. Paxillin is therefore a potential biomarker for prostate cancer proliferation and a possible therapeutic target for prostate cancer treatment.

The contributions of interleukin (IL)-17 to cancer remain unclear and somewhat controversial. We took a genetic approach to explore its role in prostate cancers by interbreeding IL-17 receptor C (IL-17RC)-deficient mice with mice that are conditionally mutant for PTEN, one established preclinical model for prostate cancer. Mice that were IL-17RC-deficient (IL-17RC(-)) displayed prostates that were smaller than mice that maintained IL-17RC expression (IL-17RC(+)). In addition, IL-17RC(-) mice developed a reduced number of invasive prostate adenocarcinomas with lower rates of cellular proliferation and higher apoptosis than IL-17RC(+) mice. Moreover, the fibromuscular stroma surrounding prostatic glands was relatively thicker in IL-17RC(-) mice and was associated with decreased matrix metalloproteinase (Mmp)7 expression and increased Timp1, 2, and 4 expression, whereas administration of recombinant mouse IL-17 induced prostatic expression of Mmp7. Taken together, our results suggested that IL-17 promotes the formation and growth of prostate adenocarcinoma, and that an IL-17-MMP7 signaling axis is required for the transition of prostatic intraepithelial neoplasia to frank adenocarcinoma. Cancer Res; 72(10); 2589-99. (c)2012 AACR.

Purpose: To assess the feasibility of diffusional kurtosis (DK) imaging for distinguishing benign from malignant regions, as well as low- from high-grade malignant regions, within the peripheral zone (PZ) of the prostate in comparison with standard diffusion-weighted (DW) imaging. Materials and Methods: The institutional review board approved this retrospective HIPAA-compliant study and waived informed consent. Forty-seven patients with prostate cancer underwent 3-T magnetic resonance imaging by using a pelvic phased-array coil and DW imaging (maximum b value, 2000 sec/mm(2)). Parametric maps were obtained for apparent diffusion coefficient (ADC); the metric DK (K), which represents non-Gaussian diffusion behavior; and corrected diffusion (D) that accounts for this non-Gaussianity. Two radiologists reviewed these maps and measured ADC, D, and K in sextants positive for cancer at biopsy. Data were analyzed by using mixed-model analysis of variance and receiver operating characteristic curves. Results: Seventy sextants exhibited a Gleason score of 6; 51 exhibited a Gleason score of 7 or 8. K was significantly greater in cancerous sextants than in benign PZ (0.96 ± 0.24 vs 0.57 ± 0.07, P < .001), as well as in cancerous sextants with higher rather than lower Gleason score (1.05 ± 0.26 vs 0.89 ± 0.20, P < .001). K showed significantly greater sensitivity for differentiating cancerous sextants from benign PZ than ADC or D (93.3% vs 78.5% and 83.5%, respectively; P < .001), with equal specificity (95.7%, P > .99). K exhibited significantly greater sensitivity for differentiating sextants with low- and high-grade cancer than ADC or D (68.6% vs 51.0% and 49.0%, respectively; P ≤ .004) but with decreased specificity (70.0% vs 81.4% and 82.9%, respectively; P ≤ .023). K had significantly greater area under the curve for differentiating sextants with low- and high-grade cancer than ADC (0.70 vs 0.62, P = .010). Relative contrast between cancerous sextants and benign PZ was significantly greater for D or K than ADC (0.25 ± 0.14 and 0.24 ± 0.13, respectively, vs 0.18 ± 0.10; P < .001). Conclusion: Preliminary findings suggest increased value for DK imaging compared with standard DW imaging in prostate cancer assessment. Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112290/-/DC1

Deng F-M, Mendrinos S E, Das K & Melamed J (2012) Histopathology 60, 1004-1008 Periprostatic lymph node metastasis in prostate cancer and its clinical significance Aims: To evaluate the potential of periprostatic lymph node (LN) as a staging indicator, particularly with the use of methods for enhanced detection of micrometastasis. Methods and results: We retrieved cases with periprostatic LN from radical prostatectomy specimens accrued between 1997 and 2007 at our institution. Twenty-one (0.8%) of 2663 radical prostatectomy specimens had periprostatic LNs (total number of LNs = 22). LN size ranged from 0.8 to 4.7 mm. Most of the periprostatic LNs were located close to the posterior base. Seven (32%) of 22 LNs were involved by metastatic prostate cancer (PCa), including five detected on routine haematoxylin and ceosin slides and an additional two detected only by immunohistochemistry. Cases with periprostatic LNs had a significantly higher metastatic rate (29%; six of 21) compared to those with pelvic LNs sampled at radical prostectatomy in our institution (1.9%). When compared to cases with negative periprostatic LNs (n = 15), the tumour characteristics of cases with metastatic periprostatic LNs (n = 6) included higher tumour volume, Gleason score, stage and a greater propensity for prostate-specific antigen (PSA) recurrence. Conclusions: Despite their infrequent identification, periprostatic LNs if detected in the radical prostatectomy specimen should be evaluated with greater scrutiny (step sections and/or immunohistochemical studies) to evaluate their prognostic potential.

Testicular germ cell tumors (TGCT) are the most common malignancy in young men. While most TGCT are potentially curable, approximately 5% of patients with TGCT may develop chemoresistance and die from the disease. This review article summarizes current knowledge in genetics underlying the development, progression and chemoresistance of TGCT. Most post-pubertal TGCT originate from intratubular germ cell neoplasia unclassified (IGCNU), which are transformed fetal gonocytes. Development of IGCNU may involve aberrantly activated KITLG/KIT pathway and overexpression of embryonic transcription factors such as NANOG and POU5F1, which leads to suppression of apoptosis, increased proliferation, and accumulation of mutations in gonocytes. Invasive TGCT consistently show gain of chromosome 12p, typically isochromosome 12p. Single gene mutations are uncommon in TGCT. KIT, TP53, KRAS/NRAS, and BRAF are genes most commonly mutated in TGCT and implicated in their pathogenesis. Different histologic subtypes of TGCT possess different gene expression profiles that reflect different directions of differentiation. Their distinct gene expression profiles are likely caused by epigenetic regulation, in particular DNA methylation, but not by gene copy number alterations. Resistance of TGCT to chemotherapy has been linked to karyotypic aberrations, single-gene mutations, and epigenetic regulation of gene expression in small-scale studies. The study of TGCT genetics could ultimately translate into development of new molecular diagnostic and therapeutic modalities for these tumors and improve the care of patients with these malignancies.

Each histologic type of renal cell carcinoma (RCC) has different pathologic and clinical parameters; however, the independent role of histologic type in outcome prediction remains contested. Most studies show relevance for outcome of each histologic type when correlated with survival by univariate analysis, whereas few studies show differences in outcome once other key prognostic factors, such as stage and grade, are considered. These studies highlight the challenges to prove outcome relevance. Despite the contested independent value of type for outcome prediction, separation of RCC into types is well accepted and can be substantiated on clinical, pathologic, molecular, and general outcome differences.

Abstract Cardiac liposarcoma is an uncommon tumor with a poor prognosis. The diagnosis and surgical treatment of this malignant tumor are the subject of this review.

PURPOSE: To assess the utility of apparent diffusion coefficient (ADC) values obtained from diffusion-weighted imaging (DWI) in distinguishing high-grade bladder cancer with and without metastatic disease. MATERIALS AND METHODS: Seventeen patients with histologically confirmed high-grade bladder cancer who underwent pelvic magnetic resonance imaging (MRI) at 1.5T including DWI using b-values of 0, 400, and 800 sec/mm(2) were assessed. Histologic findings and follow-up imaging were used to establish the reference standard in terms of metastatic disease. Two radiologists independently recorded ADC of all lesions following a training session, with their results averaged. Mann-Whitney U-test, receiver operating characteristic (ROC) curve analysis and intraclass correlation coefficient (ICC) were used for data analysis. RESULTS: Metastatic disease was characterized as present or absent in eight and nine patients, respectively. ADC was significantly lower among cases with metastatic disease than among cases without metastatic disease, both within the entire cohort (1.07 +/- 0.18 x 10(-3) mm(2) /s vs. 1.45 +/- 0.22 x 10(-3) mm(2) /s; P = 0.002) and within the subset of patients with muscle-invasive tumor (1.06 +/- 0.19 x 10(-3) mm(2) /s vs. 1.45 +/- 0.23 x 10(-3) mm(2) /s; P = 0.017). Area under the ROC curve for identifying metastatic disease using ADC was 0.944, with optimal threshold of 1.21 x 10(-3) mm(2) /s, which was associated with a sensitivity of 87.5%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 90.0%. Interreader agreement for ADC was excellent (ICC = 0.91). CONCLUSION: In this preliminary study, ADC was significantly different between cases of high-grade urothelial carcinoma of the bladder with and without metastatic disease. These results may have value in assessing the metastatic potential of patients with localized high-grade tumors of the bladder. J. Magn. Reson. Imaging 2012;. (c) 2012 Wiley Periodicals, Inc.

OBJECTIVE: The purpose of this study was to retrospectively correlate the imaging and pathologic features of multilocular cystic renal cell carcinoma (RCC), a low-grade neoplasm that has an excellent prognosis. MATERIALS AND METHODS: Institutional databases were searched for the period between 2001 and 2010 to identify cases of resected renal tumors that had been evaluated with CT or MRI and been analyzed by a uropathologist to confirm the histologic diagnosis of multilocular cystic RCC. The images (nine CT, 14 MRI) were reviewed, and a Bosniak cyst category was assigned. RESULTS: Of 23 confirmed cases of multilocular cystic RCC, imaging revealed seven lesions were Bosniak category IIF, 13 were category III, and three were category IV. Pathologic examination of the category IIF lesions revealed 99% fluid, 0.001-1% clear cells lining the septum, and 0% fibrosis. The category III lesions were 98-99% fluid, 1-2% clear cells, and 0% fibrosis. The category IV lesions were 20-40% fluid, 1-5% clear cells, and 60-80% fibrosis. The patient demographics were similar across groups. Clinical follow-up showed no evidence of recurrent or metastatic disease. CONCLUSION: Multilocular cystic RCC is a rare cystic lesion of the kidney that is low risk to the patient and benign in behavior. It has a variable imaging pattern, the Bosniak category ranging from IIF to IV. As multilocular cystic RCC lesions increase in complexity on images (higher Bosniak category), there is a corresponding increase in the volume of malignant cells lining the tumor and an increase in the presence of vascularized fibrous tissue. Regardless of the imaging appearance, the behavior of these tumors was benign in this study. Clinicians and radiologists should be aware that when this carcinoma is reported to occur, the patient has an excellent prognosis.