Quantitative perineural invasion is a prognostic marker in prostate cancer.

This study aimed to investigate the prognostic value of a quantitative, detailed, yet practical analysis of perineural invasion in radical prostatectomy specimens in a high-risk prostate cancer cohort. A total of 114 patients with prostate cancer who underwent radical prostatectomy between 2000 and 2013 were analysed. Using S100 protein immunohistochemistry assisted in the detection of nerves. In the area of closest proximity of the tumour to the dorso-lateral margins, nerves were counted and the infiltration of nerves was categorised (0-3). Category 0 was nerves without immediate tumour-cell-contact. All nerves being fully surrounded by tumour (classical perineural carcinosis) were categorised group 3. Two further categories discriminated between nerves that were touched either by carcinoma cells below 50% of the circumference (category 1) or above (category 2). Perineural carcinosis (Pn1) was seen in 61.4% of cases and correlated positively with ISUP grades, pT categories and presence of intraductal carcinoma but failed significance on Kaplan-Meier analysis. A more quantitative analysis of percentual perineural involvement did demonstrate significant survival differences: cases with less than one Pn1-positive nerve in 5 high power fields had longer survival times. Incomplete perineural involvement (category 1-2) did not have a prognostic value, endorsing the current definition of perineural carcinosis as full circumferential encasement of a nerve by tumour cells. A quantitative analysis of the percentage of nerves positive for perineural invasion has a higher prognostic value than the classical dichotomous statement on the mere presence of perineural invasion.

Prognostic significance of venous tumour thrombus consistency in patients with renal cell carcinoma (RCC).

OBJECTIVES: To identify the prognostic impact of venous tumour thrombus (VTT) in locally advanced renal cell carcinomas (RCCs). To further differentiate the clinical course of patients with VTT who have similar clinicopathological characteristics. PATIENTS AND METHODS: We determined the VTT consistency (solid vs friable) in a retrospective cohort of 200 patients with RCC who had undergone nephrectomy between 1994 and 2011. We examined the correlation of VTT consistency in these patients with clinical and pathological variables. RESULTS: A total of 65% of the patients had solid VTT and 35% had friable VTT, which has a significantly lower amount of cell-cell adhesion molecules and connective tissue than solid VTT. We found that friable VTT was associated with advanced pT stage, higher VTT level, papillary RCC subtype and a lower age. Patients with friable VTT had a significantly shorter median overall survival than those with solid VTT (29 vs 89 months), but VTT consistency was not found to be an independent predictor of patients' survival in the multivariate Cox analysis. We found that VTT consistency was an independent significant predictor of overall survival in patients without evidence of distant and nodal metastases (N = 119). CONCLUSIONS: The VTT consistency is caused by the tumour and not by different surgical handling. Friable VTT is an important adverse prognostic predictor of overall survival in patients with non-metastatic RCC.

Serum DNA hypermethylation in patients with bladder cancer: results of a prospective multicenter study.

BACKGROUND: Cell-free serum DNA levels are increased in patients with cancer, and at least partially, these DNA fragments are derived from cancer cells. A few reports indicated that methylated serum DNA in patients with bladder cancer (BCA) is a useful non-invasive biomarker. The purpose of this prospective multicenter study was to validate earlier studies. MATERIALS AND METHODS: In total, 227 consecutive participants (non-muscle invasive BCA, n=75; muscle-invasive BCA, n=20; transurethral bladder resection (TURB) without BCA, n=48; benign disease, n=31; healthy individuals, n=53), were recruited for this study. Cell-free serum DNA was isolated and digested with methylation-sensitive restriction-enzymes (Bsh1236I, HpaII and HinP1I) to quantify the amount of methylated (TIMP3, APC, RARB, TIG1, GSTP1, p14, p16, PTGS2 and RASSF1A) DNA fragments. RESULTS: The amount of methylated DNA was usually small (<10%), and the methylation frequencies varied for different genes (e.g. frequent: TIMP3; moderate: APC, RARB, TIG1; infrequent: p16, PTGS2, p14, RASSF1A, GSTP1). Methylation levels at each gene site and the number of methylated genes were increased in BCA compared to healthy individuals, but were similar in BCA and patients with non-malignant disease. The number of methylated genes allowed for discrimination (62% sensitivity, 89% specificity) of BCA patients from healthy individuals. DNA hypermethylation was not correlated with advanced stage or grade in patients with BCA. CONCLUSION: The detection of hypermethylated DNA in serum allows for discrimination of patients with BCA and healthy individuals, but there is no difference between patients with BCA and those with non-malignant disease, thereby limiting its value as a non-invasive biomarker.

Cell-free serum DNA in patients with bladder cancer: results of a prospective multicenter study.

BACKGROUND/AIM: Cell-free DNA may serve as a biomarker for patients with cancer; we designed our study to determine its potential in patients with bladder cancer (BCA). MATERIALS AND METHODS: Short ß-actin (ACTB)-106 and large ACTB-384 fragments were quantified using real time PCR (RT-PCR); the ratio of ACTB-384/ACTB-106 was defined as DNA integrity. We analyzed the serum from 95 patients with and from 132 without BCA. RESULTS: Patients with BCA had increased ACTB-106 levels and lower DNA integrity compared to patients without cancer. However, patients undergoing transurethral bladder resection (TURB) with histological exclusion of BCA had a similar ACTB-106 level and DNA integrity, as patients with BCA. Cell-free DNA was not correlated with smoker status, pT stage, grade or lymph node metastasis, or DNA integrity. There was a weak inverse correlation of age with DNA integrity in patients with BCA. CONCLUSION: Analysis of serum cell-free DNA levels and fragmentation patterns are of limited value regarding the identification of patients with BCA.

Ureteral stones due to systemic mastocytosis: diagnostic and therapeutic characteristics.

Urolithiasis is expected to cause a considerable complication in patients with systemic mastocytosis. The aim of the present report is to demonstrate that due to pathological activation and irritability of mast cells, special features in the diagnostic investigation and therapy of urolithiasis have to be considered in patients with systemic mastocytosis. The clinical presentation, diagnostic investigation and therapeutic procedure of urolithiasis in a patient with systemic mastocytosis are described. Urolithiasis may be a significant complication of systemic mastocytosis. Non-contrast CT is the main tool for diagnosing urolithiasis after a detailed history and clinical exam. Patients with systemic mastocytosis should receive a premedication composed of a glucocorticoid and H(1)- and H(2)-histamine receptor antagonists. An increased vulnerability of mucosal tissues is expected in patients with systemic mastocytosis that may limit the options of operative and postoperative therapy. Opioids should be used cautiously for analgesia in patients with systemic mastocytosis.

Saturation biopsy improves preoperative Gleason scoring of prostate cancer.

We evaluated the differences between conventional needle biopsy (CB) and saturation biopsy (SB) techniques with regard to the prediction of Gleason score, tumor stage, and insignificant prostate cancer. Data from a total number of 240 patients were analyzed. The main group, consisting of 185 patients, was diagnosed according to a saturation prostate needle biopsy protocol (SB), by which more than 12 cores were taken per biopsy. The control group was diagnosed using CB, by which 12 or less than 12 cores were taken per biopsy (n=55). In the main group, the Gleason score of the biopsy was confirmed in 19.5%, in the control group in 23.5% according to the prostatectomy specimen (p=0.50). Upgrading after the operation was found in 56.7% in the main group and in 60% in the control group (p=0.24). Downgrading after the operation was found in 23.9% in the main group and in 16.3% in the control group (p=0.24). If the Gleason score of the postoperative specimens differed by only one point from the biopsy, we considered this a minor deviation. In the main group, 59% of the carcinomas were preoperatively classified correctly or revealed minor deviation in Gleason scores. In contrast, only 47% of the carcinomas in the control group were assessed correctly or with minor deviation in Gleason scores. Thus, the main group demonstrated a better rate of preoperative prediction in tumor grading assessed by Gleason score (p=0.05). In addition, the Gleason scores of both protocols were assigned to three groups (Gleason <7; Gleason 7; Gleason >7), and the group changes from the biopsy to the prostatectomy specimen were found to be significantly more frequent in the CB group (p=0.04). There was no significant difference between the two types of biopsy techniques regarding tumor stage or the detection of insignificant carcinomas. The advantage of the extensive prostate needle biopsy technique (SB) is a better preoperative prediction of the Gleason score as well as the risk groups with Gleason scores <7, equal to 7, or >7. Both techniques fail to detect insignificant prostate cancer.

Androgen receptor coactivators lysine-specific histone demethylase 1 and four and a half LIM domain protein 2 predict risk of prostate cancer recurrence.

Prostate cancer biology varies from locally confined tumors with low risk for relapse to tumors with high risk for progression even after radical prostatectomy. Currently, there are no reliable biomarkers to predict tumor relapse and poor clinical outcome. In this study, we correlated expression patterns of the androgen receptor (AR) coactivators lysine-specific histone demethylase 1 (LSD1) and four and a half LIM-domain protein 2 (FHL2), AR, Gleason score, Gleason grade, and p53 expression in clinically organ confined prostate cancers with relapse after radical prostatectomy. Our data reveal that high levels of LSD1, nuclear expression of the FHL2 coactivator, high Gleason score and grade, and very strong staining of nuclear p53 correlate significantly with relapse during follow-up. No correlation exists with relapse and the expression of AR and cytoplasmic expression of FHL2. To confirm these data, we did quantitative reverse transcription-PCR and Western blot analyses in a subset of tumor specimens. Consistently, both LSD1 mRNA and protein levels were significantly up-regulated in high-risk tumors. We previously identified LSD1 and FHL2 as nuclear cofactors interacting specifically with the AR in prostate cells and showed that both stimulate androgen-dependent gene transcription. Our present study suggests that LSD1 and nuclear FHL2 may serve as novel biomarkers predictive for prostate cancer with aggressive biology and point to a role of LSD1 and FHL2 in constitutive activation of AR-mediated growth signals.

Neurocytoma arising in the pelvis.

Central neurocytoma represents a rare neoplasm of the central nervous system with advanced neurocytic and sometimes focal lipomatous differentiation, a low proliferative potential and a favorable prognosis depending on the efficiency of surgical resection. This entity has been described as an intraventricular tumor near the foramen Monroi. Here, we report a case of a 21-year-old male with peripheral neurocytoma. Using computed tomography, a tumor of unknown origin was located behind the bladder. After complete surgical resection of the tumor, histologically small uniform cells, zones of fibrillarity and neuropil-like islands were seen. Immunohistochemistry revealed positivity for the neuronal markers synaptophysin, neuron-specific enolase and neurofilaments. Vimentin, pan-keratin, desmin, chromogranin, CD-99 and glial fibrillary acidic protein were immuno-negative. A low proliferation rate (1-2%) was found. Several case reports described extraventricular central neurocytomas. A sole publication documented a peripheral neurocytoma arising within a mature cystic teratoma of the ovary. To our knowledge, this is the second reported case of a neurocytoma outside the central nervous system, indicating that this entity may also occur infrequently in peripheral tissues.

Primitive neuroectodermal tumor (PNET) in the differential diagnosis of malignant kidney tumors.

Primitive neuroectodermal tumors (PNETs) of the kidney, a rare neoplastic disease of high malignancy with a tendency towards early metastasis, affect young adults (26-30 years) irrespective of the gender. Differential diagnosis from other renal tumors is very important for an effective therapy. Herein, we report on a 24-year-old male patient with a renal tumor consisting of small, round cells, and summarize the diagnostic procedures that establish the diagnosis of PNET. Light microscopy revealed not only areas containing small, round cells forming rosettes and pseudorosettes, but also areas containing spindle cells. Expression of CD 99 in combination with neural markers, such as NSE, was detected by immunohistochemistry, and further evidence of neural differentiation was provided by electron microscopy. Image cytometry revealed a peridiploid DNA-stemline. A reciprocal translocation of the chromosomes 11 and 22 [t(11;22)(q24;q12)] with expression of a EWS/FLI-1 fusion transcript was demonstrated by molecular pathology. Using these methods, the diagnosis of PNET was firmly established, and the tumor was treated by surgical resection and subsequent adjuvant chemotherapy. Eighteen months after therapy, the patient is in excellent health condition without any evidence of tumor recurrence.