Lymphatic micrometastases predict biochemical recurrence in patients undergoing radical prostatectomy and pelvic lymph node dissection for prostate cancer.

BACKGROUND: Nodal metastasis is a strong prognostic parameter in prostate cancer (PCa). We analysed the detection of micrometastases (miN + ) in initially nodal-negative (pN0) radical prostatectomy specimens from pT2a-c and pT3a PCa patients by immunohistochemistry (IHC). MATERIAL AND METHODS: A total of 2352 lymph nodes of 193 PCa patients were centrally re-examined for miN + or miN- status using IHC. Results were correlated with clinical and follow-up data. Recurrence-free survival (RFS) was calculated with the log-rank test using the Kaplan-Meier method. In addition, a logistic regression analysis was performed. RESULTS: IHC detected miN + in a total of 17 patients (8.8 %). miN + seemed to be significantly associated with a higher Gleason score and was detected in more advanced pT stages. A total of 45 patients (23.1 %) had a biochemical recurrence (BCR). BCR was associated with miN +. Patients with miN + had a significantly shorter RFS (22.9 versus 58.7 months; p < 0.001). In the univariate (OR: 5.04; 95 % CI: 2.46 - 10.6; p-value: < 0.0001) and multivariate (OR: 3.29; 95 % CI: 1.54 - 7.08; p-value: 0.002) regression model, the miN + status was the strongest predictor of a BCR. CONCLUSIONS: IHC seems to be of high diagnostic value for the detection of micrometastases in initially nodal-negative PCa patients. IHC should therefore be performed in PCa patients with nodal-negative findings.

A direct comparison of contrast-enhanced ultrasound and dynamic contrast-enhanced magnetic resonance imaging for prostate cancer detection and prediction of aggressiveness.

INTRODUCTION: Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) analyse tissue vascularization. We evaluated if CEUS can provide comparable information as DCE-MRI for the detection of prostate cancer (PCa) and prediction of its aggressiveness. MATERIAL AND METHODS: A post-hoc evaluation of 92 patients was performed. In each patient CEUS and DCE-MRI parameters of the most suspicious lesion identified on MRI were analysed. The predictive values for discrimination between benign lesions, low-/intermediate- and high-grade PCa were evaluated. Results of targeted biopsy served as reference standard (benign lesions, n=51; low- and intermediate-grade PCa [Gleason grade group 1 and 2], n=22; high-grade PCa [≥ Gleason grade group 3], n=19). RESULTS: In peripheral zone lesions of all tested CEUS parameters only time to peak (TTPCEUS) showed significant differences between benign lesions and PCa (AUC 0.65). Of all tested DCE-MRI parameters, rate constant (Kep) was the best discriminator of high-grade PCa in the whole prostate (AUC 0.83) and in peripheral zone lesions (AUC 0.89). CONCLUSION: DCE-MRI showed a superior performance for detection of PCa and prediction of its aggressiveness. CEUS and DCE-MRI performed better in peripheral zone lesions than in transition zone lesions. KEY POINTS: • DCE-MRI gathers information about vascularization and capillary permeability characteristics of tissues. • DCE-MRI can detect PCa and predict its aggressiveness. • CEUS also gathers information about vascularization of tissues. • For detection of PCa and prediction of aggressiveness DCE-MRI performed superiorly. • Both imaging techniques performed better in peripheral zone lesions.

KRAS mutations in codon 12 or 13 are associated with worse prognosis in pancreatic ductal adenocarcinoma.

OBJECTIVE: Mutations in the KRAS and P53 genes belong to the most frequently observed genetic alterations in pancreatic ductal adenocarcinoma. The aim of this study was to examine the frequency and prognostic impact of KRAS mutations. In addition, we attempted to define molecular subgroups with distinct biologic behavior by combination of KRAS sequencing data with p53 protein expression data. METHODS: KRAS mutational analyses were performed in a study group of 153 patients by Sanger sequencing. Immunohistochemistry for p53 was performed on tissue microarrays. RESULTS: KRAS mutations in codon 12 or 13 were found in 68% of cases. Nuclear staining for p53 was detectable in 110 (68%) of 162 evaluable cases. We found no correlation between KRAS mutational status and p53 expression. KRAS mutational status but not p53 immunohistochemistry was an independent prognostic factor in the study group (P = 0.02). In a stratified analysis according to KRAS mutational status, p53 expression failed to define prognostic groups beyond the impact of KRAS mutational status. CONCLUSIONS: Our results support the crucial role of KRAS mutational status in pancreatic cancer biology. KRAS mutational status may serve as a prognostic marker. However, its predictive role for targeted therapies remains to be evaluated.

Interferon-stimulated gene, 15 kDa (ISG15) in ovarian high-grade serous carcinoma: prognostic impact and link to NF-κB pathway.

The ubiquitin-like protein interferon-stimulated gene, 15 kDa (ISG15) plays an ambiguous role in the progression and response to chemotherapy of solid cancers. We aimed to investigate the prognostic impact of ISG15 and its link to the nuclear factor κB pathway in ovarian high-grade serous carcinoma. Immunohistochemistry was performed in a cohort of 128 primary ovarian high-grade serous carcinomas treated with standard surgery and adjuvant chemotherapy using tissue microarrays. In addition, 28 matched relapsed carcinomas were investigated. ISG15 protein expression was significantly increased in relapsed carcinomas as compared to primary tumors (P=0.027). In primary carcinoma, ISG15 was positively associated with total inhibitor of κB α (IκBα) (P=0.001) as well as nuclear and cytoplasmic phospho-IκBα (p-IκBα) expression (P=0.039 and P=0.002, respectively). Patients with ISG15-positive carcinomas had a significantly longer overall survival in univariate analysis (P=0.002), and in multivariate analysis [hazard ratio=0.35 (95% confidence interval, 0.14-0.84, P=0.019)]. ISG15 is a potential prognostic marker in high-grade serous carcinoma of the ovary. Its impact on survival might be explained by its tight link to the nuclear factor κB pathway, and the further evaluation of the interplay between ISGylation machinery and nuclear factor κB, particularly with regard to response to chemotherapy, would be desirable.