Search

Abstract??We present two malignant cases of Sertoli?Leydig cell tumours (SLCT) of the testis and one ovarian SLCT with benign behaviour. The DNA copy number changes affected chromosome 1, 8, 9p, 10, 11, 12, 16, 19, 22 and X. The present study is the first molecular?cytogenetic analysis of Sertoli?Leydig cell tumours of the testis. [ABSTRACT FROM AUTHOR]

Microsecretory adenocarcinoma (MSA) of the salivary glands is a recently described entity. Due to lack of reported metastases, in 30 cases described until now, the designation as low-grade cancer was so far solely based on demonstration of local tumor invasion and in a single case with perineural invasion. We herein describe the first documented case with local recurrence and hematogenous metastases., (© 2022. The Author(s).)

Objectives/hypothesis: Consulting of patients with oropharyngeal carcinoma, classified as pT1pN1cM0 and pT2p/cN0cM0, about postoperative radiotherapy is a precarious task as data are lacking. The aim of this study was to evaluate the effects of postoperative radiotherapy for patients with intermediate-stage oropharyngeal carcinoma., Study Design: Multicentric retrospective study., Methods: This analysis was conducted at seven Austrian institutions and included data of patients treated between 2000 and 2012. A total of 81 patients with oropharyngeal squamous cell carcinoma were included, of whom 33 patients received postoperative radiotherapy. p16 status determined by immunohistochemistry was available in 68 patients., Results: Median follow-up was 47.9 months. Postoperative radiotherapy showed no benefits in regard to overall survival (P = .701). In contrast, disease-free survival was significantly shortened in all patients without postoperative radiotherapy (P = .001). When dividing the cohort in dependence of p16, p16-positive patients did not benefit from postoperative radiotherapy regarding overall and disease-free survival (P = .934 and P = .102), whereas p16-negative patients showed improved disease-free survival after postoperative radiotherapy (P = .007). Multivariate analysis showed that outcome of postoperative radiotherapy is dependent on p16 status., Conclusions: In terms of disease-free survival, patients with p16-negative tumors may benefit from postoperative radiotherapy, whereas survival of p16-positive patients is good regardless of additional treatment., Level of Evidence: 4. Laryngoscope, 128:1075-1082, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: Testicular neoplasms that are derived from connective tissue, blood vessels and musculature are uncommon and intra-testicular tumors of vascular origin are extremely rare; both are benign in nature. Testicular hemangioma is exceedingly rare and typically occurs in patients younger than 20 years, the age in which a primary germ cell tumor of the testis may present, necessitating a radical approach to management with orchidectomy, although potential conservative focal partial surgical excision is desirable. Hemangiomas of the testis have a similar sonographic and magnetic resonance imaging appearance to that of malignant tumors of the testis, especially seminoma. The work has been reported in line with the SCARE criteria., Presentation of Case: We present a case of testicular torsion in a 15-year-old male patient who had a painful left testis for 6 days, no vomiting, no fever or dysuria. With clinical suspicion of an old testicular torsion the patient was examined by ultrasound which confirmed the clinical diagnosis. The patient underwent emergency surgical exploration. The left testis was found to be necrotic after a 360° testicular torsion and an orchiectomy was performed., Results: The postoperative course was uneventful. The patient was discharged on day 4 after surgery. Histology showed a complete ischemic infarction of the testicular parenchyma as part of a ruptured intratesticular cavernous hemangioma., Discussion and Conclusion: Cavernous hemangioma is a rare tumor of the testicle in either childhood or adult period. The particularity of the presented case is the possible association of a cavernous intratesticular hemangioma with the torsion of the testis in a teenager. Clinicians and pathologists must be aware of the rare entity of testicular hemangiomas, as clinical examination and imaging studies do not often suffice to arrive at a correct diagnosis., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate the diagnostic accuracy of a modified scrape cell block (SCB) technique in a large series of patients. The technique was especially developed and tested for fine-needle aspiration of thyroid and parathyroid nodules., Study Design: Eighty-two ultrasound-guided fine-needle aspiration specimens with the sonographic aspect of a thyroid (n = 33) or a possible parathyroid nodule (n = 49) were studied. Immunohistochemistry (IHC) was used on cell blocks containing plasma, thromboplastin, and selected 3-dimensional cell aggregates scraped off Papanicolaou-stained smears. Antibodies for chromogranin A, thyroglobulin, parathyroid hormone, calcitonin, and carcinoembryonic antibody (CEA) were used. In cases of reduced immunosensitivity or suspected metastases or rare primary tumors, additional IHC markers were employed., Results: Chromogranin A was expressed in all 28 parathyroid adenomas (PA), in 7 of 8 hyperplastic parathyroid glands, and in 13 of 14 medullary thyroid carcinomas (MTC). When combining positivity for chromogranin A and calcitonin/CEA, the specificity for the detection of MTC was 100%. Parathyroid hormone was expressed in 26 of 36 parathyroid nodules (72.2%). When combining follicular microarchitecture and expression of chromogranin A, the specificity for the detection of parathyroid tissue was 97%., Conclusion: With the modified SCB technique, accurate cytological diagnoses were obtained in 97.6% of 82 patients., (© 2016 S. Karger AG, Basel.)

Introduction: Ependymomas are glial neoplasms that arise at or close to the inner ependymal surface of the ventricular system. They are most frequently located intraventricularly, but they may also occur in the spinal cord or, very seldom, at extraneural sites. Here we report a case of an ectopic ependymoma, arising in the pelvic cavity., Case Report: A 35 year-old female patient was diagnosed with a suspect tumor mass in the rectovaginal space, infiltrating the perirectal adipose tissue and the vagina. Three years later, liver and peritoneal metastases of the same tumor were diagnosed. Two years after that, the patient experienced a recidive in the left adnexa. Histological analysis revealed an anaplastic tumor of dual nature, comprising of mesenchymal and epithelial features. There were ependymoma-like rosettes and pseudorosettes, indicating an ependymal differentiation. Immunohistochemically, the tumor was positive for epithelial membrane antigen (EMA) and glial fibrillary acidic protein (GFAP). Accordingly, the diagnosis "grade 3 ependymoma, i.e. ependymoblastoma" was made., Review: Ependymomas are most frequently located in the ventricular system, but may also occur in the spinal cord or rarely at extraneural sites. Extraneural ependymomas represent a diagnostic challenge, since they can mimic other tumor types and the immunohistochemical profile may be non-specific. The most important features of ependymal differentiation are rosette- or pseudorosette formation. Extraneural ependymomas can be located in the ovary or elsewhere in the pelvic cavity. Locations in the lung, liver and the small bowel have also been described. In the present article we review several reported cases of ectopic, extraneural ependymomas., Discussion: The origin of extraneural ependymomas is not completely clarified. They probably arise from glial tissue that is a residue from the embryonic development, pinched-off from the neural tube during its closure. We propose, that extraneural ependymoma should be considered in differential diagnosis for anaplastic tumors of the pelvic cavity.

Prostate cancer is a common cause of death, and an important goal is to establish the pathways and functions of causative genes. We isolated RNAs that are differentially expressed in macrodissected prostate cancer samples. This study focused on 1 identified gene, TTLL12, which was predicted to modify tubulins, an established target for tumor therapy. TTLL12 is the most poorly characterized member of a recently discovered 14-member family of proteins that catalyze posttranslational modification of tubulins. We show that human TTLL12 is expressed in the proliferating layer of benign prostate. Expression increases during cancer progression to metastasis. It is highly expressed in many metastatic prostate cancer cell lines. It partially colocalizes with vimentin intermediate filaments and cellular structures containing tubulin, including midbodies, centrosomes, intercellular bridges and the mitotic spindle. Downregulation of TTLL12 affects several posttranslational modifications of tubulin (detyrosination and subsequent deglutamylation and polyglutamylation). Overexpression alters chromosomal ploidy. These results raise the possibility that TTLL12 could contribute to tumorigenesis through effects on the cytoskeleton, tubulin modification and chromosome number stability. This study contributes a step toward developing more selective agents targeting microtubules, an already successful target for tumor therapy.

Background: Insulin-like growth factor binding protein 3 (IGFBP-3) exerts inhibitory and proapoptotic effects on prostate cancer cells. Serum levels of IGFBP-3 were found to be associated with the risk of prostate cancer, but the data are still inconclusive. We present a detailed analysis of the expression and localization of IGFBP-3 in the prostate and a comparison with its expression pattern in tumors., Methods: Expression and localization of IGFBP-3 were analyzed in cellular models and tissue by real-time RT-PCR, ELISA, immunohistochemistry, and immunofluorescence., Results: All cell types of a panel of benign epithelial, stromal and tumor prostate cells expressed IGFBP-3. Significantly higher expression levels were registered in stromal cells. TGF-beta stimulation boosted IGFBP-3 levels 60-fold in stromal cells. The pattern of expression was confirmed in microdissected tissue samples. Protein levels measured by ELISA paralleled the mRNA levels and more than 80% of IGFBP-3 was secreted. On tissue immunostaining, IGFBP-3 was found to be mainly located in the epithelium. The pattern suggested secretion of IGFBP-3, which was confirmed in prostate tissue cultured ex vivo and the ejaculate of vasectomized men. IGFBP-3 levels were increased in primary tumors but did not differ from benign epithelium in metastases and local recurrent tumors., Conclusions: We registered a significant local production of IGFBP-3 in the prostate, which may well override the effect of protein entering from blood. The stroma--particularly reactivated stroma--is the main source of IGFBP-3 in the prostate, suggesting that this peptide acts as a mediator of stromal-epithelial interactions., (Copyright (c) 2008 Wiley-Liss, Inc.)

Precancer (carcinoma in situ) or laryngeal intraepithelial neoplasia (LIN) is a non-invasive lesion that has genetic abnormalities, loss of cellular control functions, and some phenotypic characteristics of invasive cancer and that predicts for a substantial likelihood of developing invasive cancer. Several classifications have been proposed but none has received a total agreement. With regard to diagnosis, treatment and prognosis, these lesions differ substantially from infiltrating carcinoma. Known risk factors include cigarette smoking, viral infection with subtypes of the human papilloma virus, exposure to asbestos, and probably the gastro-oesophageal reflux disease. The diagnostic work-up usually includes indirect laryngoscopy with rigid telescopes, microlaryngoscopy and biopsies for histological evaluation. Therapeutic options include wait-and-see-strategies, radiotherapy, transoral laser surgery, vocal cord stripping with cold instruments, and open partial laryngectomy. Data from the literature suggest highest local control rate with radiotherapy as initial treatment compared to other standard methods of management of dysplasia. However, transoral laser surgery can be applied repeatedly and yields excellent final results. Therefore it is now considered the treatment of choice for these lesions in the majority of patients. Local recurrences are observed more frequently than with small infiltrative carcinoma, and second primaries may arise within the upper aero-digestive tract following initial treatment. Therefore systematic follow-up is recommended for these patients.

Sertoli cell tumours (SCT) are rare and poorly explored neoplasias, and the genetic features of these uncommon tumours are largely unknown. Data about chromosomal aberrations in human SCT of the testis are very rare. We present in this paper the first molecular-cytogenetic study of SCT of the testis. DNA was isolated from paraffin-embedded tumour material from 11 patients with unilateral SCT. We used comparative genomic hybridisation to investigate changes in DNA copy number. The detected DNA imbalances showed variation from case to case, indicating a high genetic heterogeneity. Chromosomal aberrations were detected in 9 of the 11 tumours evaluated, with 13 losses versus 14 gains. The most frequent aberrations detected were gain of chromosome X (5 of 11 cases) followed by losses of entire or part of chromosomes 2 and 19 in three cases. This study suggests a high variability in histomorphological and genetic patterns. Only gain of the entire chromosome X seems to be a frequent aberration in these tumours. Further studies of these tumour types are necessary to clarify the significance of chromosomal alterations in carcinogenesis of SCT.

We present two malignant cases of Sertoli-Leydig cell tumours (SLCT) of the testis and one ovarian SLCT with benign behaviour. The DNA copy number changes affected chromosome 1, 8, 9p, 10, 11, 12, 16, 19, 22 and X. The present study is the first molecular-cytogenetic analysis of Sertoli-Leydig cell tumours of the testis.

Background: Focal atrophy is presumed to be an indirect forerunner of prostate cancer. The aim of this study was to examine genetic alterations in prostate epithelia deriving from atrophic areas and compare these findings with those of cells deriving from paired prostate cancer in the same patient., Methods: Formalin fixed paraffin wax-embedded prostatectomy specimens from 20 prostate cancer patients were utilized in this study. Comparative Genomic Hybridization (CGH) was performed on atrophic areas. To validate the CGH results, Fluorescence in Situ Hybridization (FISH) analysis was performed on atrophic areas and paired cancer tissue., Results: Gain of the whole chromosome X was found as sole aberration in seven (70%) atrophic tissues by CGH. A gain of centromere X was observed in 13 (68.4%) atrophic areas and in 18 (90%) cancer tissues using FISH., Conclusions: Our investigation reconfirms the genetical instability of cells of the atrophic acini and attention of relevance of gain of chromosome X in atrophic areas.

The genetic features of the uncommon Leydig cell tumors (LCT) are largely unknown. Consequently, it is of great importance to elucidate the pathogenesis of testicular germ cell tumors by cytogenetic and molecular biological investigations. The purpose of the present study was the examination of cytogenetic features of these tumors in a large series of LCT. It comprised formalin-fixed, paraffin-embedded tissue samples from 25 LCT to analyze the chromosomal constitution using comparative genomic hybridization (CGH). In most of the studied cases, the aberrant cell population was additionally defined by interphase fluorescence in situ hybridization (I-FISH). Our molecular-cytogenetic study indicates chromosomal imbalances in the majority of our cases (21/25, 84%). The most frequent findings were gain of chromosome X, 19 or 19p and loss on chromosome 8 and 16.

Objectives: The purpose of this study was to evaluate, according to a classification proposed by a working group, the extent and type of atrophy lesions in radical prostatectomy specimens obtained from patients with prostatic carcinoma and benign prostatic hyperplasia (BPH), and to compare the prevalence and types of atrophy between two investigated groups., Methods: Histologic analysis of 1096 slides from 50 patients with carcinoma and 277 slides from 31 patients with BPH was performed to evaluate, according to the new prostatic atrophy classification, the number of foci and type of atrophic lesions., Results: Age, Gleason grade, and TNM showed no significant correlation with the number of proliferative atrophy (PA) and proliferative inflammatory atrophy (PIA) foci (p>0.05). PIA was significantly more frequent in prostates with carcinoma (1.63 vs 1.27 atrophic lesions per slide) (p<0.001), whereas PA displayed an increased frequency in BPH (2.28 vs 0.76 atrophic lesions per slide) (p<0.001)., Conclusions: We confirmed that PA and PIA are common findings in prostates with and without carcinoma, but the question of whether inflammation produces tissue damage and PA or whether some other insult induces the tissue damage and atrophy directly, with inflammation occurring secondarily, is still unresolved.

A differential quantitative protein expression study, comparing matched prostate cancerous and benign tissues from 31 patients, revealed proteins newly associated with prostate cancer. Average effects for 17 proteins whose abundance was significantly different (p<0.01) across patients ranged from 1.5- to 6.1-fold, and included a number of known cancer markers. The most differentially abundant proteins between cancer and benign samples were isopeptidase T, serum amyloid P (SAP), annexin A3 (ANXA3) and mitochondrial enoyl coenzyme-A hydratase. SAP is restricted to stroma in healthy tissue, and the lower abundance in tumours may be explained by the reduced stromal content. ANXA3 is present in healthy epithelial cells, exhibits strong staining in precancerous prostatic intraepithelial neoplasia, and is relatively less abundant in individual tumour cells of increasing Gleason pattern (GP), despite exhibiting higher overall tissue abundance in tumours. ANXA3 staining was predominantly cytoplasmic, yet nuclear localization was also observed. Strongly staining single cells, possibly phagocytes, were interspersed in highly dedifferentiated GP5 tumour areas among tumour cells without measurable ANXA3. Local recurrent androgen ablation therapy-resistant tumours exhibit heterogenous low levels of ANXA3 staining. Results are discussed focussing on the potential implications for tumour tissues.

Objective: To systematically examine the genetic alterations on chromosome 8 in prostate epithelia deriving from atrophic areas, and to compare these alterations with those of cells derived from prostatic intraepithelial neoplasia (PIN) and prostate cancer in the same organ., Material and Methods: Tissue microarrays were constructed from 50 patients with histologically different tissues, including normal, PIN, atrophy and cancer lesions. Control samples were obtained from 10 patients who died from causes other than prostate cancer. Multicolour DNA probes for 8p22, centromere 8 and 8q24 were used to detect genetic alterations by fluorescence in situ hybridisation analysis., Results: Chromosomal alterations were detected on chromosome 8 in all analysed tissues. Including all observed signal patterns, a gradual increase of nuclei with loss of 8p22 was detected in normal (16%), in atrophy (21%), in PIN (25%) and in cancer tissue (31%), and there was gain in 8q24 in normal tissue (10%), in atrophy lesions (19%), in PIN (21%) and in cancer (27%). Generally, in all three lesion types the percentage of cells with 8q24 gain was significantly lower than the percentage of cells with loss of 8p22., Conclusion: This investigation confirms the presence of severe chromosomal aberrations in the epithelium of the atrophic glands of the prostate. The aberrations are the same those that can be found in PIN and in prostate cancer. These findings confirm the genetic instability of the cells in the atrophic areas of the prostate, which can be a target for further injuries, leading to prostate cancer.

Purpose: ATF3 is a member of the basic leucine zipper/cyclic adenosine monophosphate responsive element binding protein family of transcription factors. There is overwhelming evidence that it is a stress inducible factor acting in a signal-type and cell-type dependent manner, and it is involved in cell proliferation and survival. We found that ATF3 was differently expressed in an in vitro prostate cancer tumor progression model and we investigated the possible role of ATF3 in prostate cancer., Materials and Methods: ATF3 up-regulation in vivo/in vitro and androgen regulation were assessed by immunohistochemistry and immunoblot analysis. Results after forced ATF3 transfection were evaluated by proliferation assay and cell cycle analysis., Results: Immunohistochemistry and immunoblot analysis revealed ATF3 up-regulation in prostate cancer in vitro and in vivo, and stimulation of expression by androgens. Antiandrogen treatment decreased ATF3 expression in androgen sensitive cells but acted as a stimulator in long-term androgen ablated cells representing a model for therapy refractory disease. Expression in tumors increased with higher Gleason scores and highest expression was observed in samples of therapy refractory tumor tissue. Forced ATF3 over expression in a prostate cancer cell line induced cell proliferation and accelerated cell cycle progression from G1 to S-phase., Conclusions: These data provide new insight into the role of ATF3 in prostate cancer development and/or progression. They indicate that ATF3 is an androgen regulated gene that is highly expressed in prostate tumors and stimulating cell proliferation. It represents a possible target for prostate cancer therapy.

Background: In contrast to Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disorders (PTLD), EBV-associated leiomyomatous tumors have thus far only rarely been described., Case Report: Two years after heart transplantation with ATG induction, cyclosporine (CsA; trough levels of 250 ng/mL)-based triple drug immunosuppression), a 23-year-old patient developed a small round lesion within the left lateral liver segment. The patient underwent ultrasound-guided biopsy followed by liver resection. Histological and immunohistological examination showed a leiomyosarcoma. In situ hybridization using EBV-specific EB endoplasmic reticulum-RNA showed an intensive signal in almost all tumor cells. The tumor stained for EB nuclear antigen (EBNA)-2-protein. Immunosuppression was drastically reduced, namely, CsA levels <100 ng/dL, prednisolone 5 mg, azathioprine withdrawn, and antiviral chemotherapy initiated with 10 days of IV gancyclovir and acyclovir followed by oral famcyclovir. During the follow-up, anti-EBV-IgM, anti-early antigen antibodies, and anti-EBNA antibodies were continuously monitored excluding significant EBV replication. Eighteen months post-liver resection, and high-resolution computed tomography scan demonstrated two paravertebral tumors. These lesions and a small nodule at the left ankle were resected revealing identical leiomyosarcomata. Immunosuppression was further reduced (CsA levels 75 ng/dL) and famcyclovir maintenance therapy started. Nevertheless, 2 years later the patient again developed tumor recurrence (perirectal, liver, and right adrenal gland); the tumors were surgically removed. The therapy was switched to Rapamycin and famcyclovir was continued. Three years after the last surgical intervention, the patient is well and recurrence-free., Conclusion: Long-term survival in patients with posttransplant EBV-associated leiomyosarcoma can be achieved by combined surgical intervention, reduction of immunosuppression, switch to Sirolimus, and antiviral chemotherapy.

Background: The neo-angiogenetic microvessels forming a major reactive stromal element in highly malignant prostate neoplasms may exhibit fine-structural features relevant to our understanding of the passage of macromolecules from tumor to blood, on the one hand, and of events facilitating the metastatic cascade, on the other hand., Methods: Ensuring rapid, optimal fixation in buffered glutaraldehyde was a foremost concern. Thin parings from radical prostatectomy specimens of Gleason scores (GS) 5-9 were taken from the tumor and from the contralateral side of the gland, glutaraldehyde-fixed, diced to smaller than 1 mm(3), postfixed in osmium tetroxide, embedded in Epon, ultrathin-sectioned, contrasted with lead and uranyl salts, and viewed in a transmission electron microscope., Results: In dysplastic tissue areas, intraductal microvessels located in gland ducts were occasionally observed, and found to be aggressively invasive and highly active in producing neo-angiogenetic sprouts. Closely spaced microvessel clusters contained almost exclusively neo-angiogenetic microvessels, which were in cell-cell contact with numerous ameboid migratory cells, some of which were likely to be tumor cells. In these microvessel clusters, all structural barriers hindering passage of tumor-derived molecules or cells to the blood were eliminated., Conclusion: In microvessel clusters, the ultrastructural equivalent of microvascular hotspots, tumor invasion of microvessels is facilitated, but equally microvessels are observed invading the gland duct epithelial walls. This reciprocal invasivity of tumor cells and microvascular endothelial cells generates ideal conditions for tumor products and metastatic cells to enter the blood., (Copyright 2004 Wiley-Liss, Inc.)

One of the underemphasized supportive criteria for the diagnosis of prostatic cancer is the presence of retraction clefting around neoplastic glands. We analyzed a series of 152 prostatic cancer cases to determine the frequency, extent, and correlation of periacinar retraction clefting between needle core biopsies (NCB) and corresponding matched radical prostatectomy (RP) specimens. Clefting was significantly more frequent in neoplastic compared to nonneoplastic acini in NBC and RP (p<0.05). There was no significant difference in the frequency of retraction clefting in neoplastic acini between NCB and corresponding RP (p>0.05). We have also found a concordance in matched RP and NCB (Kappa=0.582). We conclude that periacinar retraction clefting appears more frequently in neoplastic acini and could serve as a reliable criterion in the diagnosis of prostatic adenocarcinoma.

We performed comparative genomic hybridization (CGH) on 8 formalin-fixed, paraffin wax-embedded primary spermatocytic seminomas (SS) from 7 patients, one of whom developed metastatic disease. In general, this tumour type is not associated with development of metastases. Since there are only few reported cases of metastatic SS in the literature, this study is the first report of chromosomal constitution in a patient with metastatic disease. Chromosomal imbalances were observed in all 8 tumours analysed by CGH. Frequent copy number alterations were enh(9), dim(16 or 16p), enh(20) and enh(X), each in 6 samples, followed by dim(7) in 4, and enh(1), enh(18) and dim(15), each in 3 samples. In addition to the CGH analysis, interphase fluorescence in situ hybridisation (I-FISH) was applied to evaluate the CGH results and to define the size of the aberrant cell population. Interphase cytogenetics showed gain of material on chromosomes 9 and X in all tumours analysed. Overall, the I-FISH results were in agreement with the CGH data. In conclusion, gain of chromosome 9 seems to be restricted to SS and point to an important role for this aberration in the development of this tumour type., (Copyright (c) 2004 Pathological Society of Great Britain and Ireland.)

We report a case of bilateral synchronous malignant mesothelioma of the testis. A 21-year-old man presented with an acute scrotum after 3 months of recurrent pain on the right side. Ultrasonography demonstrated an irregular thickening of the tunica vaginalis testis, scrotolyths, and an increased blood flow to the right epididymis testis. Bilateral exploration revealed torsion of the hydatid and a bilateral malignant mesothelioma of the tunica vaginalis. One year later, elective bilateral exploration showed one minute area on the parietal tunica vaginalis of malignant mesothelioma. After 2 years of follow-up, the patient had no signs of distant disease.

Aims: Tenascin-C (Tn-C) is an extracellular matrix glycoprotein that is upregulated in malignant tumours. Tn-C promotes cell growth, cell migration, and angiogenesis. It has been suggested to be a prognostic factor in various types of malignant tumours, but there is little information on its significance in bladder cancer with regard to overall survival (OS) and recurrence free survival (RFS)., Methods: Tn-C expression was studied in 106 patients with bladder cancer diagnosed between 1994 and 1997. Immunohistochemistry was performed using a monoclonal antibody against Tn-C. RFS and OS were estimated by the Kaplan-Meier method and compared by the log rank test in univariate analysis and by the Cox multistep regression method in multivariate analysis., Results: Within the mean follow up period of 126 months, patients with diffuse Tn-C staining in the tumour stroma had a significantly worse OS than those with negative staining or only moderate Tn-C expression (p = 0.025). Patients with cytoplasmic expression of Tn-C had a significantly better OS than those without (p = 0.001). Multivariate analysis, taking into consideration age, grade, stage, tumour associated carcinoma in situ, progression, and Tn-C staining in tumour stroma, showed that only expression of Tn-C in invasive tumour cells was an independent positive prognostic factor for OS (p = 0.049)., Conclusions: Tn-C may provide important prognostic information in bladder cancer depending on the expression pattern in the tumour stroma or cytoplasm of the tumour cells.

Purpose: We assessed the complication rate of ultrasound guided prostate biopsies performed at a single center in a screening population. Moreover the impact of different biopsy protocols comprising varying numbers of biopsy cores on the complication rate was evaluated., Materials and Methods: A total of 5957 biopsies performed in 4303 clinically healthy men between January 1993 and August 2002 was evaluated retrospectively. Due to changes in the biopsy protocol, the number of biopsies obtained increased with time from 6 cores (January 1993 to October 1995) to 10 (November 1995 to March 2000) to 15 cores (March 2000 to August 2002)., Results: Minor complications such as hematospermia (36.3%), hematuria (14.5%) and rectal bleeding persisting for up to 2 days (2.3%) were noted frequently, while major complications requiring further treatment were far less common. Post-biopsy fever was seen in 48 patients (0.8%), rectal bleeding requiring surgical intervention or persisting for more than 2 days occurred in 36 patients (0.6%) and urinary retention was observed in 12 patients (0.2%). The increase in biopsy cores with time did not result in increased post-biopsy morbidity. Prostate cancer at biopsy was not associated with a higher complication rate., Conclusions: Prostate specific antigen screening has led to an increase in the number of patients undergoing prostate biopsy which, in turn, has increased the incidence of post-biopsy complications. However, most of the complications are minor and self-limiting. In this large study population the increased number of biopsy cores did not result in an increased incidence of major post-biopsy complications.

Background: When age-referenced PSA levels as recommended by Oesterling et al.1 were used as a biopsy criterion, only 25% of the cancers detected in a population based PSA Screening Project were organ-confined. This observation led to the decision to use low PSA levels as the sole indication for biopsy. Since 1995 age-referenced PSA levels of 1.25-3.25 ng/ml have been used in combination with a percentage free PSA cutoff of 18%. This PSA cutoff reduction led to a statistically significant migration to lower pathological stages with a decreased prostate cancer mortality in the years 1996-2001. However, concerns have been raised that screening with low PSA levels may detect clinically insignificant cancers., Materials and Methods: We evaluated prostate cancer patients with low PSA levels in terms of heterogeneity, clinical significance, multifocality, and tumor biology including ploidy and proliferation index., Results: Concerning heterogeneity the Gleason score of the needle biopsy failed to predict the Gleason score of the radical prostatectomy specimen in nearly 40% of prostate cancer patients; regarding multifocality 65% of patients with low PSA levels showed multifocal lesions and 36% exhibited tetraploid DNA distribution; more than 50% of tetraploid tumors were found in patients with tumor volumes of less than 0.5 cm(3). Ploidy correlated with the Ki-67 proliferation index, but not with tumor volume., Conclusions: These results demonstrate that small prostate cancers with low PSA levels and low tumor volumes exhibit all features of prostate cancers with higher tumor volumes and show the characteristics of malignant cancers, i.e., multifocality, tetraploidy, and high proliferative activity., (Copyright 2003 Wiley-Liss, Inc.)

Background: The present study was designed to investigate whether the clinical or pathologic features of prostate cancer (PCa) are related to the number of repeat biopsies required to establish the diagnosis of PCa., Methods: Between February 1993 and August 2000, 653 patients were evaluated in this retrospective study. All patients underwent transrectal ultrasound-guided biopsy of the prostate prior to radical retropubic prostatectomy. The pathologic findings of specimens obtained at radical prostatectomy and pelvic lymph node dissection as well as PSA levels, findings on DRE, prostate volumes, transition zone volumes, and age were analyzed separately for all PCa patients diagnosed at the first set of biopsies (group A) and compared with the data of those diagnosed at the 2nd-5th set of biopsies (group B). In a second step, we compared the results obtained from patients diagnosed at the 2nd set of biopsies (group B1) with those of patients diagnosed at the 3rd to 5th set of biopsies (group B2)., Results: Gleason scores, pathologic tumor stages, and tumor volumes in group B were found to be significantly decreased compared to group A. But from the 2nd to 5th serial biopsy no further decrease in pathologic stage, Gleason score, or tumor volume was observed. On the contrary, there was a tendency towards higher tumor stages and Gleason scores. Of the tumors detected after the second false-negative set of biopsies almost 70% were lesions with Gleason scores of 6 or higher., Conclusions: False-negative results at the first needle biopsy are predictive of a lower pathologic stage and grade as well as smaller tumor volumes of PCa diagnosed at repeat sets of biopsies. False-negative results on repeat biopsy, however, have no prognostic significance for the tumor stage of PCas detected at subsequent sets of biopsies., (Copyright 2003 Wiley-Liss, Inc.)