Correlation between enhancement characteristics of MR mammography and capillary density of breast lesions.

OBJECTIVE: To correlate capillary density of breast lesions using the markers D2-40, CD31, and CD34 with early and late enhancement of magnetic resonance mammography (MRM). MATERIALS AND METHODS: The local ethics committee approved this study, and informed consent was avail-able from all patients. The study included 64 women with 66 histologically proven breast lesions (41 malignant, 25 benign). MR-enhancement 1 min after contrast medium administration was determined in the tumor (It1/It0 ratio) and in comparison to the surrounding tissue (It1/It1-fat ratio). Capillary density was quantified based on immunohistological staining with D2-40, CD31, and CD34 in breast tumors and surrounding breast tissue. Mean capillary densities were correlated with contrast enhancement in the tumor and surrounding breast tissue. The Kruskal-Wallis test was used to test whether lesions with different MR enhancement patterns differed in terms of capillary density. RESULTS: For CD34, there was statistically significant correlation between capillary density and tumor enhancement (r = 0.329, p = 0.012), however not for the malignant or benign groups separately. Mean vessel number identified by staining with D2-40 and CD31 did not correlate significantly with tumor enhancement (D2-40: r = -0.188, p = 0.130; CD31: r = 0.095, p = 0.448). There were no statistically significant differences in capillary density between breast lesions with delayed enhancement or a plateau and lesions showing washout (Kruskal-Wallis test. D2-40: p = 0.173; CD31: p = 0.647; CD34: p = 0.515). CONCLUSION: Of the three markers tested, CD34 showed best correlation between early contrast enhancement on MRM and capillary density. Further studies are necessary to clearly demonstrate an association between capillary density and contrast enhancement in breast tumors and surrounding tissue.

ASPP2 controls epithelial plasticity and inhibits metastasis through ß-catenin-dependent regulation of ZEB1.

Epithelial to mesenchymal transition (EMT), and the reverse mesenchymal to epithelial transition (MET), are known examples of epithelial plasticity that are important in kidney development and cancer metastasis. Here we identify ASPP2, a haploinsufficient tumour suppressor, p53 activator and PAR3 binding partner, as a molecular switch of MET and EMT. ASPP2 contributes to MET in mouse kidney in vivo. Mechanistically, ASPP2 induces MET through its PAR3-binding amino-terminus, independently of p53 binding. ASPP2 prevents ß-catenin from transactivating ZEB1, directly by forming an ASPP2-ß-catenin-E-cadherin ternary complex and indirectly by inhibiting ß-catenin's N-terminal phosphorylation to stabilize the ß-catenin-E-cadherin complex. ASPP2 limits the pro-invasive property of oncogenic RAS and inhibits tumour metastasis in vivo. Reduced ASPP2 expression results in EMT, and is associated with poor survival in hepatocellular carcinoma and breast cancer patients. Hence, ASPP2 is a key regulator of epithelial plasticity that connects cell polarity to the suppression of WNT signalling, EMT and tumour metastasis.

Loss of anterior gradient-2 expression is an independent prognostic factor in colorectal carcinomas.

AIMS: The human Anterior Gradient-2 (AGR2) protein is strongly expressed in various human cancers, and it has been described to promote aggressive tumour features in some entities. So far, a comprehensive analysis of AGR2 expression in colorectal carcinomas has not been described. METHODS: Normal intestinal cells and colorectal carcinoma cell lines were analysed for AGR2 expression. AGR2 protein expression was immunohistochemically analysed in 28 normal tissue samples and 1068 tissue samples of clinically well characterised colorectal carcinomas. For statistical analysis, chi square test, spearman rank correlations, Kaplan-Meier estimates (Log rank test) and Cox regression were applied to test for diagnostic or prognostic associations. RESULTS: In the normal intestinal cell line and in normal colon mucosa AGR2 was found in all cases (n=28). In contrast, loss of AGR2 was found in all six analysed colorectal cancer cell lines and in 833/1068 (78%) of the colorectal carcinoma tissue samples analysed, and it was significantly associated with a higher tumour grade and tumour localisation in the left-sided colon. In addition to the conventional prognostic tumour parameters pT category, nodal status, metastasis and histological tumour grade the loss of AGR2 expression was significantly associated with reduced overall survival times in univariate and multivariate analyses, thus suggesting AGR2 as an independent prognostic factor in primary colorectal carcinoma. CONCLUSIONS: AGR2 is frequently lost in colorectal carcinomas and might be a novel independent prognostic factor for overall patient survival.

ASPP2 suppresses squamous cell carcinoma via RelA/p65-mediated repression of p63.

Squamous cell carcinoma (SCC) is highly malignant and refractory to therapy. The majority of existing mouse SCC models involve multiple gene mutations. Very few mouse models of spontaneous SCC have been generated by a single gene deletion. Here we report a haploinsufficient SCC mouse model in which exon 3 of the Tp53BP2 gene (a p53 binding protein) was deleted in one allele in a BALB/c genetic background. Tp53BP2 encodes ASPP2 (ankyrin repeats, SH3 domain and protein rich region containing protein 2). Keratinocyte differentiation induces ASPP2 and its expression is inversely correlated with p63 protein in vitro and in vivo. Up-regulation of p63 expression is required for ASPP2(Δexon3/+) BALB/c mice to develop SCC, as heterozygosity of p63 but not p53 prevents them from developing it. Mechanistically, ASPP2 inhibits ΔNp63 expression through its ability to bind IκB and enhance nuclear Rel/A p65, a component of the NF-κB transcription complex, which mediates the repression of p63. Reduced ASPP2 expression associates with tumor metastasis and increased p63 expression in human head and neck SCCs. This study identifies ASPP2 as a tumor suppressor that suppresses SCC via inflammatory signaling through NF-κB-mediated repression of p63.

Comparison of EndoPredict and Oncotype DX test results in hormone receptor positive invasive breast cancer.

AIM: Several multigene expression-based tests offering prognostic and predictive information in hormone-receptor positive early breast cancer were established during the last years. These tests provide prognostic information on distant recurrences and can serve as an aid in therapy decisions. We analyzed the recently validated reverse-transcription-quantitative-real-time PCR-based multigene-expression Endopredict (EP)-test on 34 hormone-receptor positive breast-cancer cases and compared the EP scores with the Oncotype DX Recurrence-scores (RS) obtained from the same cancer samples. METHODS: Formalin-fixed, paraffin-embedded invasive breast-cancer tissues from 34 patients were analyzed by the EP-test. Representative tumor blocks were analyzed with Oncotype DX prior to this study. Tumor tissue was removed from unstained slides, total-RNA was isolated and EP-analysis was performed blinded to Oncotype DX results. RESULTS: Extraction of sufficient amounts of RNA and generation of valid EP-scores were possible for all 34 samples. EP classified 11 patients as low-risk and 23 patients as high-risk. RS Score defined 15 patients as low-risk, 10 patients as intermediate-risk in and 9 patients as high-risk. Major-discrepancy occurred in 6 of 34 cases (18%): Low-risk RS was classified as high-risk by EP in 6 cases. Combining the RS intermediate-risk and high-risk groups to a common group, the concordance between both tests was 76%. Correlation between continuous EP and RS-scores was moderate (Pearson-coefficient: 0.65 (p<0.01). CONCLUSION: We observed a significant but moderate concordance (76%) and moderate correlation (0.65) between RS and EP Score. Differences in results can be explained by different weighting of biological motives covered by the two tests. Further studies are needed to explore the clinical relevance of discrepant test results with respect of outcome.

Occupational health risks of pathologists--results from a nationwide online questionnaire in Switzerland.

BACKGROUND: Pathologists are highly trained medical professionals who play an essential part in the diagnosis and therapy planning of malignancies and inflammatory diseases. Their work is associated with potential health hazards including injuries involving infectious human tissue, chemicals which are assumed to be carcinogenic or long periods of microscope and computer work. This study aimed to provide the first comprehensive assessment of the health situation of pathologists in Switzerland. METHODS: Pathologists in Switzerland were contacted via the Swiss Society of Pathologists and asked to answer an ethically approved, online anonymous questionnaire comprising 48 questions on occupational health problems, workplace characteristics and health behaviour. RESULTS: 163 pathologists participated in the study. Forty percent of pathologists reported musculoskeletal problems in the previous month. The overall prevalence was 76%. Almost 90% of pathologists had visual refraction errors, mainly myopia. 83% of pathologists had experienced occupational injuries, mostly cutting injuries, in their professional career; more than one fifth of participants reported cutting injuries in the last year. However, long lasting injuries and infectious diseases were rare. Depression and burnout affected every eighth pathologist. The prevalence of smoking was substantially below that of the general Swiss population. CONCLUSIONS: The results of this study suggest that more care should be taken in technical and personal protective measures, ergonomic workplace optimisation and reduction of work overload and work inefficiencies. Despite the described health risks, Swiss pathologists were optimistic about their future and their working situation. The high rate of ametropia and psychological problems warrants further study.

Tubular and endothelial chimerism in renal allografts using fluorescence and chromogenic in situ hybridization (FISH, CISH) technology.

The role of endothelial and tubular chimerism in renal allograft adaptation and rejection varies in different studies. We addressed the correlation between different clinico-pathological settings and sex-chromosomal endothelial and/or tubular chimerism in renal allografts. We examined the presence or absence of the X and Y chromosomes by fluorescence and chromogenic in situ hybridization (FISH, CISH) methodology on paraffin embedded kidney biopsies in 16 gender mismatched renal transplants (1 to 12 years post-transplantation). Twelve patients were male, four female. Four groups were selected: (i) Vascular calcineurin inhibitor toxicity without rejection; (ii) T-cell mediated vascular rejection; (iii) antibody mediated rejection; and (iv) C4d-positivity in AB0-incompatible transplants with or without rejection. Twelve non-transplant kidney biopsies (8 female, 4 male) were used as controls. Tubular chimerism was detected more frequently (69%) than endothelial chimerism (12%) in renal transplants. One of 12 control patients had tubular and endothelial chimeric cells (8%). The Y chromosome occurred in 8/12 male recipients (67%) in tubular epithelial cells and in 5/12 male recipients (42%) in endothelial cells. Double X chromosomes were detected in 3/4 female recipients in tubular epithelium. Tubular chimerism occurred more often with endothelial chimerism and capillaritis without correlation with other parameters, such as rejection. Combined Y chromosomal tubular and lymphatic endothelial chimerism correlated with T-cell mediated vascular rejection in two out of three patients (66%). Combined Y chromosomal tubular and peritubular capillary chimerism correlated with antibody mediated C4d+ rejection in one out of two patients (50%). Tubular and/or endothelial chimerism occur frequently in gender mismatched renal allografts and, when combined, this is associated with T-cell mediated rejection.

Insulin-like growth factor II mRNA-binding protein 3 (IMP3) expression in hepatocellular carcinoma. A clinicopathological analysis with emphasis on diagnostic value.

AIMS: Patients with hepatocellular carcinoma (HCC) usually present with advanced disease and rarely qualify for curative therapy. Immunohistochemical markers that help to discriminate benign from malignant processes early, and that have prognostic significance, would be useful. Expression of the oncofetal protein insulin-like growth factor II mRNA-binding protein 3 (IMP3) in malignant cells of different tumour types correlates with reduced overall survival. METHODS AND RESULTS: Tissue microarrays (TMAs) containing 55 normal liver samples, 365 HCCs (122 with corresponding non-tumorous liver), 10 hepatocellular adenomas, 13 focal nodular hyperplasias and nine dysplastic nodules from western European patients were stained for IMP3. IMP3 was analysed in 61 core needle biopsies and findings were compared to glypican-3 and CD34. HCCs in TMAs were strongly positive for IMP3 in 18.4% of cases compared to absent expression in normal and non-tumorous liver tissue and benign liver tumours. Patients with IMP3 expression in HCCs showed significantly poorer overall survival in multivariate analysis (P = 0.044). Of the 61 core needle biopsies analysed, 32 (52.5%) of the HCCs were IMP3-positive. CONCLUSIONS: In core needle biopsies, IMP3 expression seems to be of limited use as a single marker for the diagnosis of HCC, given a sensitivity of 52%, but it may be helpful in combination with other markers.

Expression of histone deacetylases 1, 2 and 3 in histological subtypes of testicular germ cell tumours.

In this study we aimed to evaluate the protein expression of class I histone deacetylases (HDAC) in testicular germ cell tumours (GCT) and to analyse differences between the histological subtypes of testicular GCT. 325 testicular GCT were included in a tissue microarray with each histological subtype of the tumour being separately represented on this array. Expression of class I HDAC isoforms 1, 2 and 3 was assessed by immunohistochemistry. While HDAC2 and 3 were highly expressed in all histological subtypes of GCT, HDAC1 was almost consistently expressed at lower levels. We observed significant differences in the expression of the respective HDACs between seminoma and non-seminoma GCT tissue components. Interestingly, choriocarcinomas showed generally high expression values for all three class I HDAC isoforms. Relevant correlations with clinicopathological parameters could not be demonstrated. Contrasting published findings on other tumour entities, no immediate practical diagnostic or prognostic value for HDAC1-3 in GCT could be inferred. However, the high expression levels might still be indicative for a treatment response to HDAC inhibitors which ought to be evaluated in further studies.

MAGEC2 is a sensitive and novel marker for seminoma: a tissue microarray analysis of 325 testicular germ cell tumors.

Melanoma-associated gene C2 (MAGEC2) is a recently identified cancer testis antigen expressed in normal testicular and placental tissue. It has been detected in some human carcinomas, but its expression in primary testicular germ cell tumors is unknown. Immunohistochemistry was used to study MAGEC2 protein in 325 primary testicular germ cell tumors, including 94 mixed germ cell tumors. Seminomatous and non-seminomatous components were separately arranged and evaluated on tissue microarrays. MAGEC2 expression was compared with POU5F1 (OCT3/4), SOX2, SOX17, KIT and TNFRSF8 (CD30). The mouse monoclonal anti-MAGEC2 antibody (clone LX-CT10.5) revealed a nuclear MAGEC2 expression with little or no background staining. MAGEC2 expression was found in 238 of 254 seminomas (94%), but not in embryonal carcinomas (n=89). POU5F1 (OCT3/4) was positive in 97% of seminomas and all embryonal carcinomas. In contrast, KIT was positive in 94% of seminoma but also in 8% of embryonal carcinomas. TNFRSF8 (CD30) and SOX2 were negative in seminoma and positive in embryonal carcinoma (96 and 90%, respectively). SOX17 was positive in 94% of seminoma and negative in embryonal carcinoma. We conclude that MAGEC2 allows a reliable distinction of seminoma from embryonal carcinomas. Therefore, MAGEC2 represents an additional tool for the differential diagnosis of testicular germ cell tumors.

Silver-enhanced in situ hybridization for detection of polyomavirus DNA in patients with BK virus nephropathy.

BK virus nephropathy is not an infrequent complication of renal transplantation associated with high rates of graft loss. Although antibodies against SV40 antigen detect different viruses of the polyomavirus family, immunohistochemistry is widely used to confirm the diagnosis of BK virus nephropathy in renal biopsies. Here we aimed to validate the novel silver-enhanced in situ hybridization (SISH) technique for the automated detection of BK virus in renal transplant biopsies. Two different patient cohorts were included. Twenty-nine consecutive patients suspicious for BK virus infection were investigated by SISH and chromogenic in situ hybridization. An additional 26 renal biopsies positive by SV40 immunohistochemistry from 19 patients were analyzed by SISH. Polyomavirus DNA serum levels, as determined by nested PCR analysis, were available for all of these patients. The presence of BK virus DNA in renal tubular cells was identified in 5 of the suspicious cases by both, SISH and chromogenic in situ hybridization . One additional patient was only positive in the SISH. In the second cohort, SISH was positive in all SV40 positive biopsies, but SISH signals were less extensive than SV40 immunohistochemistry. Our results show that the BK virus SISH is an ancillary tool for the detection of polyomavirus DNA in renal biopsies using bright-field microscopy. However, its diagnostic value in comparison with standard immunohistochemistry seems to be limited.

The androgen-regulated Calcium-Activated Nucleotidase 1 (CANT1) is commonly overexpressed in prostate cancer and is tumor-biologically relevant in vitro.

Previously, we identified the calcium-activated nucleotidase 1 (CANT1) transcript as up-regulated in prostate cancer. Now, we studied CANT1 protein expression in a large cohort of nearly 1000 prostatic tissue samples including normal tissue, prostatic intraepithelial neoplasia (PIN), primary carcinomas, metastases, and castrate-resistant carcinomas, and further investigated its functional relevance. CANT1 displayed predominantly a Golgi-type immunoreactivity with additional and variable cytoplasmic staining. In comparison to normal tissues, the staining intensity was significantly increased in PIN lesions and cancer. In cancer, high CANT1 levels were associated with a better prognosis, and castrate-resistant carcinomas commonly showed lower CANT1 levels than primary carcinomas. The functional role of CANT1 was investigated using RNA interference in two prostate cancer cell lines with abundant endogenous CANT1 protein. On CANT1 knockdown, a significantly diminished cell number and DNA synthesis rate, a cell cycle arrest in G(1) phase, and a strong decrease of cell transmigration rate and wound healing capacity of CANT1 knockdown cells was found. However, on forced CANT1 overexpression, cell proliferation and migration remained unchanged. In summary, CANT1 is commonly overexpressed in the vast majority of primary prostate carcinomas and in the precursor lesion PIN and may represent a novel prognostic biomarker. Moreover, this is the first study to demonstrate a functional involvement of CANT1 in tumor biology.

Podoplanin expression correlates with sentinel lymph node metastasis in early squamous cell carcinomas of the oral cavity and oropharynx.

In patients with early head and neck squamous cell carcinoma (HNSCC), occult lymph node metastasis is difficult to predict by clinical or pathological parameters. However, such parameters are necessary to select patients either for elective neck dissection or the sentinel lymph node (SLN) procedure. The membrane glycoprotein podoplanin is normally expressed in lymphatic endothelial cells. Recently, expression of podoplanin by cancer cells was demonstrated to promote tumor cell motility and tumor lymphangiogenesis in vitro. The value of cancer cell-expressed podoplanin was to be determined as a predictive marker for SLN metastasis in early HNSCC of the oral cavity and oropharynx. One hundred twenty patients with HNSCC of the oral cavity and oropharynx undergoing a SLN biopsy were enrolled in this prospective clinical trial of SLN biopsy. Cancer cell-expressed podoplanin was determined by immunohistochemistry using tissue microarrays. Podoplanin expression was quantified by the intensity reactivity score and categorized into expression and nonexpression. SLN examination revealed occult metastasis in 45 patients (37.5%). Twenty-nine of 120 (24.2%) primary HNSCC showed podoplanin expression. Podoplanin expression correlated significantly with SLN metastasis (p = 0.029) and remained a significant predictor for lymph node status even after controlling for tumor stage (p = 0.028). As a predictive marker for SLN metastasis, however, podoplanin expression reached a sensitivity of a mere 36% and a specificity of 83%. Podoplanin expression is associated with metastasis to lymph nodes in vivo. Podoplanin immunohistochemistry in early HNSCC of the oral cavity and oropharynx may help to select patients for the SLN procedure and to identify patients with increased risk for presence of occult lymph node metastasis in the neck.

Radiological and pathological findings of a metastatic composite paraganglioma with neuroblastoma in a man: a case report.

INTRODUCTION: Composite tumors of the adrenal medulla or paraganglia are extremely rare and present a diagnostic dilemma. These tumors consist of a neuroendocrine component mixed with a neural component.We describe the imaging characteristics together with the corresponding pathological findings of a composite tumor. Apart from any component-specific imaging findings, the hallmark of this entity is the presence of histologically distinguishable components. CASE PRESENTATION: A 61-year-old Caucasian man was referred to our hospital due to a suspect lesion found on chest computed tomography carried out for unclear thoracic pain. An abdominal computed tomography scan and ultrasound examination detected a retroperitoneal tumor comprising two different tumor components. Twenty-four-hour urine revealed high levels of normetanephrine, characteristic of a neuroendocrine tumor. An octreoscan prior to surgical procedures revealed multiple osseous and intra-hepatic metastases. The final histopathological workup revealed a composite paraganglioma with neuroblastoma. Our patient died ten months after the initial diagnosis from tumor-associated complications. CONCLUSIONS: Composite paragangliomas with neuroblastoma are rare tumors of the retroperitoneum. Such tumors should be considered in the differential diagnosis of retroperitoneal masses.

Novel markers in zero-hour kidney biopsies indicate graft quality and clinical outcome.

BACKGROUND: In renal transplantation, allograft biopsies provide valuable diagnostic information indicating adverse allograft outcome posttransplantation. To uncover novel candidate markers characteristic of subtle inflammation and immune activation present during the intraoperative period, we investigated messenger RNA (mRNA) gene expression profiles in renal zero biopsies. METHODS: Transcription profiles from deceased donors (n=63) and living donors (n=26) were investigated for inflammation-associated markers in zero-hour biopsies by real-time reverse-transcriptase polymerase chain reaction. RESULTS: We observed a significant induction of the chemokine receptor 7 ligands [C-C motif] ligand 19/21 in the deceased donor group (P<0.001). Additionally, along with the induction of the activation marker CD69 (P<0.01), we further detected significant elevated mRNA levels of the inducible immunoproteasome subunits PSMB8, PSMB9, and PSMB10 (P<0.001, respectively). Candidate markers were further tested for posttransplantation clinical outcomes showing the potential to predict the development of delayed graft function, acute rejection, and renal function after 6 months. For instance, by combining mRNA gene expression profiles with clinical patient data, the analysis revealed high sensitivity (95%) and specificity (84%, area under the curve=0.93) for the prediction of acute rejection. CONCLUSIONS: Zero-hour biopsies of renal allografts may provide useful information on subclinical pathological changes in the grafted kidney. The identification of CCL19/21 or PSMB8/9/10 makes these molecules particularly suitable as potential candidate targets for therapeutic interventions.

Determination of the Her-2/neu gene amplification status in cytologic breast cancer specimens using automated silver-enhanced in-situ hybridization (SISH).

Silver-enhanced in-situ hybridization (SISH) is an emerging tool for the determination of the Her-2/neu amplification status in breast cancer. SISH is technically comparable to fluorescence in-situ hybridization (FISH) but does not require a fluorescence microscope for its interpretation. Although recent studies on histologic evaluations of SISH are promising, we aimed to evaluate its performance on 71 cytologic breast cancer specimens with the new combined Her-2/Chr17 probe. Her-2/neu status as routinely determined by FISH was available for all patients. We found SISH signals in cytologic cell blocks and smear specimens easy to evaluate in most cases. Small numbers of tumor cells and difficulties in identifying tumor cells in lymphocyte-rich backgrounds were limiting factors. Her-2/neu status, as determined by Her-2/Chr17 SISH, was basically identical to the results of the corresponding FISH. The discrepancies were mainly owing to the heterogeneity of Her-2/neu amplification in the tumor tissue. Interobserver agreement for the SISH evaluation was high (kappa value: 0.972). We conclude that Her-2/Chr17 SISH is a useful and accurate method for the evaluation of the Her-2/neu gene amplification status in cytologic breast cancer specimens, particularly in metastatic breast cancer lesions. The advantages of signal permanency and bright-field microscopic result interpretation make this technique an attractive alternative to the current FISH-based gold standard.

Insulin-like growth factor II mRNA binding protein 3 (IMP3) is overexpressed in prostate cancer and correlates with higher Gleason scores.

BACKGROUND: The oncofetal protein insulin-like growth factor II mRNA binding protein 3 (IMP3) is an important factor for cell-migration and adhesion in malignancies. Recent studies have shown a remarkable overexpression of IMP3 in different human malignant neoplasms and also revealed it as an important prognostic marker in some tumor entities. To our knowledge, IMP3 expression has not been investigated in prostate carcinomas so far. METHODS: Immunohistochemical stainings for IMP3 were performed on tissue microarray (TMA) organized samples from 507 patients: 31 normal prostate tissues, 425 primary carcinomas and 51 prostate cancer metastases or castration-resistant prostate cancers (CRPC). IMP3 immunoreactivity was semiquantitatively scored and correlated with clinical-pathologic parameters including survival. RESULTS: IMP3 is significantly stronger expressed in prostate carcinomas compared to normal prostate tissues (p < 0.0001), but did not show significant correlation with the pT-stage, the proliferation index (MIB1), preoperative serum PSA level and the margin status. Only a weak and slightly significant correlation was found with the Gleason score and IMP3 expression failed to show prognostic significance in clinico-pathological correlation-analyses. CONCLUSIONS: Although IMP3 is overexpressed in a significant proportion of prostate cancer cases, which might be of importance for novel therapeutic approaches, it does not appear to possess any immediate diagnostic or prognostic value, limiting its potential as a tissue biomarker for prostate cancer. These results might be corroborated by the fact, that two independent tumor cohorts were separately reviewed.

Pulmonary Kaposi's sarcoma after heart transplantation: a case report.

INTRODUCTION: Kaposi's sarcomas have been associated with different conditions of immunosuppression and are also known to be a typical complication of solid organ transplantations. CASE PRESENTATION: We report the case of a 65-year-old Turkish man with a history of heart transplantation 10 months ago who presented for clarification of his dyspnea. The patient had a known history of chronic obstructive pulmonary disease and a smoking history of 40 pack years. Radiologically, three progressively growing intra-pulmonary nodules were detected. The histology was diagnostic for a Kaposi's sarcoma. Visceral and especially primary intra-pulmonary Kaposi's sarcomas are very rare and have been described to have a rather unfavorable prognosis. CONCLUSIONS: Even with a history suggestive for conventional lung cancer, Kaposi's sarcomas should be considered in patients after transplantation of solid organs. It should be noted that in a minority of cases this tumor exists in the absence of the typical cutaneous lesions.

Periostin is up-regulated in high grade and high stage prostate cancer.

BACKGROUND: Expression of periostin is an indicator of epithelial-mesenchymal transition in cancer but a detailed analysis of periostin expression in prostate cancer has not been conducted so far. METHODS: Here, we evaluated periostin expression in prostate cancer cells and peritumoural stroma immunohistochemically in two independent prostate cancer cohorts, including a training cohort (n = 93) and a test cohort (n = 325). Metastatic prostate cancers (n = 20), hormone refractory prostate cancers (n = 19) and benign prostatic tissues (n = 38) were also analyzed. RESULTS: In total, strong epithelial periostin expression was detectable in 142 of 418 (34.0%) of prostate carcinomas and in 11 of 38 benign prostate glands (28.9%). Increased periostin expression in carcinoma cells was significantly associated with high Gleason score (p < 0.01) and advanced tumour stage (p < 0.05) in the test cohort. Whereas periostin expression was weak or absent in the stroma around normal prostate glands, strong periostin expression in tumour stroma was found in most primary and metastatic prostate cancers. High stromal periostin expression was associated with higher Gleason scores (p < 0.001). There was a relationship between stromal periostin expression and shortened PSA relapse free survival times in the training cohort (p < 0.05). CONCLUSIONS: Our data indicate that periostin up-regulation is related to increased tumour aggressiveness in prostate cancer and might be a promising target for therapeutical interventions in primary and metastatic prostate cancer.