Publications by authors named "Piotr Czapiewski"

43 Publications

Eukaryotic Translation Initiation Factor 4AI: A Potential Novel Target in Neuroblastoma.

Cells 2021 Feb 2;10(2). Epub 2021 Feb 2.

Diagnostic and Research Center for Molecular BioMedicine, Diagnostic and Research Institute of Pathology, Medical University of Graz, 8010 Graz, Austria.

Neuroblastoma (NB) is the most common extracranial pediatric solid tumor. Children suffering from high-risk and/or metastatic NB often show no response to therapy, and new therapeutic approaches are urgently needed. Malignant tumor development has been shown to be driven by the dysregulation of eukaryotic initiation factors (eIFs) at the translation initiation. Especially the activity of the heterotrimeric eIF4F complex is often altered in malignant cells, since it is the direct connection to key oncogenic signaling pathways such as the PI3K/AKT/mTOR-pathway. A large body of literature exists that demonstrates targeting the translational machinery as a promising anti-neoplastic approach. The objective of this study was to determine whether eIF4F complex members are aberrantly expressed in NB and whether targeting parts of the complex may be a therapeutic strategy against NB. We show that eIF4AI is overexpressed in NB patient tissue using immunohistochemistry, immunoblotting, and RT-qPCR. NB cell lines exhibit decreased viability, increased apoptosis rates as well as changes in cell cycle distribution when treated with the synthetic rocaglate CR-1-31-B, which clamps eIF4A and eIF4F onto mRNA, resulting in a translational block. Additionally, this study reveals that CR-1-31-B is effective against NB cell lines at low nanomolar doses (≤20 nM), which have been shown to not affect non-malignant cells in previous studies. Thus, our study provides information of the expression status on eIF4AI in NB and offers initial promising insight into targeting translation initiation as an anti-tumorigenic approach for NB.
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http://dx.doi.org/10.3390/cells10020301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912938PMC
February 2021

ALK alterations in salivary gland carcinomas.

Virchows Arch 2020 Nov 25. Epub 2020 Nov 25.

Department of Pathomorphology, Medical University of Gdańsk, ul. Smoluchowskiego, 17 80-211, Gdańsk, Poland.

Salivary gland carcinomas represent a heterogeneous group of poorly characterized head and neck tumors. The purpose of this study was to evaluate ALK gene and protein aberrations in a large, well-characterized cohort of these tumors. A total of 182 salivary gland carcinomas were tested for anaplastic lymphoma kinase (ALK) positivity by immunohistochemistry (IHC) using the cut-off of 10% positive cells. ALK positive tumors were subjected to FISH analysis and followed by hybrid capture-based next generation sequencing (NGS). Of the 182 tumors, 8 were ALK positive by IHC. Further analysis using hybrid capture NGS analysis revealed a novel MYO18A (Exon1-40)-ALK (exon 20-29) gene fusion in one case of intraductal carcinoma. Additional genomic analyses resulted in the detection of inactivating mutations in BRAF and TP53, as well as amplifications of ERBB2 and ALK. ALK rearrangements are a rare entity in salivary gland carcinomas. We identified a potentially targetable novel ALK fusion in an intraductal carcinoma of minor salivary glands.
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http://dx.doi.org/10.1007/s00428-020-02971-wDOI Listing
November 2020

Immunohistochemical evaluation of mismatch repair proteins and p53 expression in extrauterine carcinosarcoma/sarcomatoid carcinoma.

Contemp Oncol (Pozn) 2020 30;24(1):1-4. Epub 2020 Mar 30.

Department of Pathomorphology, Medical University of Gdansk, Gdansk, Poland.

Introduction: Carcinosarcoma (CS) is a tumor with components: epithelial (carcinomatous) and mesenchymal (sarcomatous), developing in the mechanism of epithelial-mesenchymal transition. It is known that the p53 defect is a frequent finding in a carcinosarcoma in different anatomical locations, additionally, in a subgroup of uterine CS MMR defect plays a role in the pathogenesis. The aim of this paper was to investigate the frequency of MMR and p53 aberrations in extrauterine CS.

Material And Methods: Twenty eight extrauterine CS from the lung ( = 8), breast ( = 6), head and neck ( = 5), ovary ( = 3), urinary bladder ( = 3), adrenal gland ( = 1), skin ( = 1), and stomach ( = 1) were stained for hMLH1, PMS2, hMSH2, hMSH6 and p53. The pattern of expression was evaluated separately in carcinomatous and sarcomatous component.

Results: Immunostainings for hMLH1, PMS2, hMSH2 and hMSH6 were positive in all tumors. p53 defect was observed in 19 out of 28 samples (67.85%). In all cases except one (96.42%) there was a concordance between sarcomatoid and carcinomatous components.

Conclusions: MMR deficiency does not seem to play a role in the pathogenesis of extrauterine CS. p53 aberrant expression is frequent and almost always consistent in carcinomatous and sarcomatous component.
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http://dx.doi.org/10.5114/wo.2020.94718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265955PMC
March 2020

promoter hypermethylation in uterine carcinosarcoma rarely coexists with mutation.

Contemp Oncol (Pozn) 2019 7;23(4):202-207. Epub 2019 Nov 7.

Department of Pathomorphology, Medical University of Gdansk, Poland.

Introduction: Carcinosarcoma (CS) is an infrequent neoplasm composed of a carcinomatous and a sarcomatous element. Its molecular pathogenesis is poorly understood. In this study, we investigated the disturbances in the immunohistochemical expression of p53 and mismatch repair (MMR) proteins, as well as their molecular background.

Material And Methods: The study group consisted of 20 uterine CSs. We analysed their morphology and immunohistochemical expression of hMLH1, hPMS2, hMSH2, MSH6, and p53 as well as the presence of mutations in and promoter methylation of the hMLH1. Loss of hMLH1 and PMS2 was found in 3/20 tumours. All cases were positive for hMSH2 and hMSH6. The mutation was detected in 8/19 tumours (42.1%), whereas promoter hypermethylation in 4/19 cases (21%), and one case with synchronous aberrations (5%). Agreement between the results of the genetic and immunohistochemical study was moderate for p53 (k = 0.615, < 0.01) and strong for (k = 0.826, < 0.01).

Results And Conclusions: We demonstrated promoter hypermethylation in uterine CS, leading to loss of immunostaining. Concomitant aberrations of p53 and hMLH1 are infrequent. It is likely that uterine CS may develop in two independent molecular pathways in association with either chromosomal or microsatellite instability.
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http://dx.doi.org/10.5114/wo.2019.89635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978758PMC
November 2019

The Prognostic Significance of Eukaryotic Translation Initiation Factors (eIFs) in Endometrial Cancer.

Int J Mol Sci 2019 Dec 6;20(24). Epub 2019 Dec 6.

Area 2 Cancer, Center for Biomarker Research in Medicine, Stiftingtalstraße 5, 8010 Graz, Austria.

Whilst the role of eukaryotic translation initiation factors (eIFs) has already been investigated in several human cancers, their role in endometrial cancer (EC) is relatively unknown. In the present retrospective study, 279 patients with EC (1180 samples) were included (mean age: 63.0 years, mean follow-up: 6.1 years). Samples were analysed for expression of 7 eIFs subunits (eIF2α, eIF3c, eIF3h, eIF4e, eIF4g, eIF5, eIF6) through immunohistochemistry and western blotting. Fifteen samples of healthy endometrium served as controls. Density and intensity were assessed and mean combined scores (CS) calculated for each patient. Upon immunohistochemistry, median eIF5 CS were significantly higher in EC as compared with non-neoplastic tissue (NNT, < 0.001), whilst median eIF6 CS were significantly lower in EC ( < 0.001). Moreover, eIF5 ( = 0.002), eIF6 ( = 0.032) and eIF4g CS ( = 0.014) were significantly different when comparing NNT with EC grading types. Median eIF4g CS was higher in type II EC ( = 0.034). Upon western blot analysis, eIF4g ( < 0.001), peIF2α ( < 0.001) and eIF3h ( < 0.05) were significantly overexpressed in EC, while expression of eIF3c was significantly reduced in EC as compared with NNT ( < 0.001). The remaining eIFs were non-significant. Besides tumour stage ( < 0.001) and patient's age ( < 0.001), high eIF4g CS-levels were independently associated with poor prognosis (HR: 1.604, 95%CI: 1.037-2.483, = 0.034). The other eIFs had no prognostic significance. Notably, the independent prognostic significance of eIF4g was lost when adding tumour type. Considering the difficulties in differentiating EC type I and II, eIF4g may serve as a novel prognostic marker indicating patient outcome.
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http://dx.doi.org/10.3390/ijms20246169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941158PMC
December 2019

ALK-rearranged renal cell carcinomas in Polish population.

Pathol Res Pract 2019 Dec 25;215(12):152669. Epub 2019 Sep 25.

Department of Pathomorphology, Medical University of Gdansk, Mariana Smoluchowskiego 17, 80-214 Gdansk, Poland. Electronic address:

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase, the activation of which is considered an important event in the pathogenesis of several neoplasms and a predictive factor for the targeted therapy with ALK inhibitors. Thus far, ALK rearrangements have been identified in 22 renal cell carcinomas in both pediatric and adult patients. We evaluated the incidence of ALK rearrangement-associated RCC in adult Central European population. An immunohistochemical evaluation of 1019 kidney tumors was performed with use of three different clones of anti-ALK antibodies. None of the tested samples showed positive staining, which suggests that the incidence of ALK rearrangement-associated renal cell carcinomas is significantly lower in the Polish population, and indicates a potential association between ethnicity and occurrence of these rare neoplasms.
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http://dx.doi.org/10.1016/j.prp.2019.152669DOI Listing
December 2019

CD70 expression correlates with a worse prognosis in malignant pleural mesothelioma patients via immune evasion and enhanced invasiveness.

J Pathol 2020 02 3;250(2):205-216. Epub 2019 Dec 3.

Department of Pathology, Aichi Medical University School of Medicine, Nagakute, Japan.

Diffuse malignant mesothelioma of the pleura (MPM) is a highly aggressive tumour that typically is associated with short survival. CD70 and CD27 belong to the tumour necrosis factor (TNF) and the TNF receptor (TNFR) superfamily, respectively. Under physiological conditions, the tightly regulated interaction between CD70 and CD27 plays a co-stimulatory role in promoting T-cell expansion and differentiation through the NFκB pathway. Aberrantly high CD70 expression has been documented in haematological and solid malignancies in association with immune evasion in malignant cells. In this study, 172 well-characterised primary diffuse MPM tumours including epithelioid (n = 145), biphasic (n = 15), and sarcomatoid (n = 12) histotypes were evaluated immunohistochemically for CD70, CD27, CD3, CD4, CD8, CD56, PDCD1 (PD-1), and FOXP3 expression. Twenty per cent (34/172) of the mesothelioma cells expressed CD70 on the cell membrane. Overall survival was significantly decreased in the cohort of patients with CD70-expressing tumour cells (p < 0.01). Patients with MPM containing a higher number of CD3 (p < 0.01), CD4 (p < 0.01), CD8 (p < 0.01), or FOXP3 (p < 0.01) tumour-infiltrating lymphoid cells (TILs) showed significantly worse clinical outcomes. As potential independent risk factors for MPM patients, multivariate Cox proportional hazards regression analysis revealed CD70 expression on mesothelioma cells [hazard ratio (HR) 2.25; p = 0.010], higher FOXP3 TILs (HR 2.81; p = 0.004), and higher CD3 TIL accumulation (HR 6.12; p < 0.001). In contrast, as a potential independent favourable factor, higher CD27 TIL accumulation (HR 0.48; p = 0.037) was identified. In vitro experiments and an immunodeficient mouse model revealed that CD70 enhances the invasiveness of MPM cells through MET-ERK axis activation. Further analyses in syngeneic mouse models demonstrated possible roles for CD70 in immune evasion. Collectively, these findings suggest that the CD70-CD27 pathway enhances the malignant phenotypes of MPM and diminishes anti-tumor immune response in patients with these neoplasms. These markers might be useful in MPM for prognostic evaluations as well as targeted therapeutics. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/path.5361DOI Listing
February 2020

The "Optimum Volume" of Acrylic Cement Filling for Treating Vertebral Compression Fractures: A Morphometric Study of Thoracolumbar Vertebrae.

Adv Exp Med Biol 2019 ;1211:25-39

Second Department of Radiology, Medical University of Gdansk, Gdansk, Poland.

Percutaneous vertebroplasty is a treatment option in vertebral compression fractures (VCF). The aim of the study was to propose the mathematical calculation of the "optimum volume" of acrylic cement filling of the vertebral body, depending on the severity of a fracture. Two hundred computed tomography (CT) scans of vertebral columns in healthy adult Caucasians were analyzed. Vertebral body width (VBW), vertebral body depth (VBD), vertebral body height (VBH), and vertebral body volume (VBV) were measured. The "optimum volume" of cement injections in mild (25% collapse) and moderate (40% collapse) VCF were calculated. We found that moving caudally from Th to L, the mean values of the examined parameters increased: VBH from 22.6 to 26.0 mm, VBW from 34.0 to 39.5 mm, VBD from 28.1 to 30.9 mm, and VBV from 17.1 to 24.8 cm. The calculated hypothetical "optimum volume" of cement injection increased from 7.4 to 10.0 cm in mild VCF and from 5.9 to 7.8 cm in moderate VCF, with some variability depending on the vertebral level and gender. These values are akin to those present in other past studies. We conclude that morphometric measurements, based on CT images, are a reliable source of practical anatomical savvy, which may be of help in spine surgery.
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http://dx.doi.org/10.1007/5584_2019_417DOI Listing
November 2019

Impact of EMT in stage IIIB/IV NSCLC treated with erlotinib and bevacizumab when compared with cisplatin, gemcitabine and bevacizumab.

Oncol Lett 2019 Jun 15;17(6):4891-4900. Epub 2019 Mar 15.

Department of Thoracic Oncology, University Hospital Heidelberg and Translational Lung Research Center Heidelberg, Member of The German Center for Lung Research, D-69126 Heidelberg, Germany.

The aim of the present study was to assess the expression of epithelial-mesenchymal transition biomarkers (E-cadherin and vimentin) and their potential significance as prognostic markers in patients with stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC) enrolled in the INNOVATIONS trial, receiving treatment with either erlotinib/bevacizumab (EB) or cisplatin/gemcitabine/bevacizumab (PGB). The tumor tissues of 104 patients were retrospectively analyzed using immunohistochemistry to assess the expression of E-cadherin and vimentin. The distribution between the treatment arms was 46 patients in the EB-arm and 58 in the PGB-arm. Comparing the treatment arms according to E-cadherin and vimentin expression, the analysis revealed that progression-free survival (PFS) was increased in the PGB treatment group when compared with EB treatment in patients with low expression of E-cadherin [hazard ratio (HR)=0.353; 95% confidence interval (CI) 0.189- 0.658; log-rank P=0.0007] and in those with high expression of vimentin [HR=0.276 (95% CI, 0.115- 0.659), log-rank P=0.0021]. In patients that exhibited high E-cadherin and were negative for vimentin, there was no difference in the PFS between the PGB and EB treatment groups. In conclusion, in non-squamous NSCLC with downregulated E-cadherin and upregulated vimentin, the efficacy of chemotherapy with PGB was superior compared with EB; but the same effect was not observed in patients with high E-cadherin and low vimentin. Although increased PFS was observed in patients with PGB treatment compared with EB treatment in the whole analysis populations, in the subgroup of patients with the mesenchymal phenotype, no prognostic or predictive value of either biomarker could be identified. The potential role of bevacizumab in overcoming chemotherapy resistance in the population with the mesenchymal phenotype has to be further explored.
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http://dx.doi.org/10.3892/ol.2019.10153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507446PMC
June 2019

Prognostic value of broad-spectrum keratin clones AE1/AE3 and CAM5.2 in small cell lung cancer patients undergoing pulmonary resection.

Acta Biochim Pol 2019 Feb;66(1):111-114

7Department of Oncology and Radiotherapy, Medical University of Gdansk, Poland.

Introduction: Small cell lung carcinoma (SCLC) is an aggressive pulmonary neoplasm of neuroendocrine origin. Keratins form a large group of intermediate filaments, which are major structural proteins in epithelial cells and carcinomas. SCLC shows a wide spectrum of keratin expression, from very strong to completely negative. A prognostic role of keratin expression in SCLC is unknown.

Material And Methods: Tumor tissue microarray samples from a unique series of 82 SCLC patients who underwent pulmonary resection were stained with keratin specific antibodies AE1/AE3 and CAM5.2. The percentage o1f positively stained cells and their staining pattern (diffusely membranous, partially membranous and dot-like) were evaluated. The median expression value was used for the distinction between keratin-negative and -positive patients. Overall survival in respective groups was compared using the log-rank test. Multivariate Cox proportional hazards regression analysis was performed adjusting for age, gender, tumor site, tumor stage, and tumor histology.

Results: edian expression of AE1/AE3 and CAM5.2 was 80% and 90%, respectively. Five cases were completely negative for AE1/AE3 and three for Cam5.2. Median overall survival for patients with stronger and weaker AE1/AE3 staining was 24.7 and 13.8 months, respectively (p=0.019). There was no difference in survival in relation to the CAM5.2 expression (p=0.44). In multivariate analysis adjusted for CAM5.2, T and N stage, gender and age at diagnosis, stronger AE1/AE3 expression was an independent predictor of increased survival (HR 0.50; 95% CI, 0.27-0.94; p=0.031).

Conclusion: High expression of AE1/AE3 is a favorable prognostic factor in surgically treated SCLC. The applicability of this finding to a typical patient population treated with non-surgical methods warrants further studies.
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http://dx.doi.org/10.18388/abp.2018_2773DOI Listing
February 2019

Morphometric Analysis of the Lumbar Vertebrae Concerning the Optimal Screw Selection for Transpedicular Stabilization.

Adv Exp Med Biol 2019;1133:83-96

Second Department of Radiology, Faculty of Health Sciences, Medical University of Gdansk, Gdansk, Poland.

Transpedicular stabilization is a frequently used spinal surgery for fractures, degenerative changes, or neoplastic processes. Improper screw fixation may cause substantial vascular or neurological complications. This study seeks to define detailed morphometric measurements of the pedicle (height, width, and surface area) in the aspects of screw length and girth selection and the trajectory of its implantation, i.e., sagittal and transverse angle of placement. The study was based on CT examinations of 100 Caucasian patients (51 women and 49 men) aged 27-75 with no anatomical, degenerative, or post-traumatic spine changes. The results were stratified by gender and body side, and they were counter compared with the available literature database. Pedicle height decreased from L1 to L4, ranging from 15.9 to 13.3 mm. Pedicle width increased from L1 to L5, extending from 6.1 to 13.2 mm. Pedicle surface area increased from L1 to L5, ranging from 63 to 140 mm. Distance from the point of entry into the pedicle to the anterior surface of the vertebral body, defining the maximum length of a transpedicular screw, varied from 54.0 to 50.2 mm. Variations concerning body sides were inappreciable. A transverse angle of screw trajectory extended from 20° to 32°, shifting caudally from L1 to L5, with statistical differences in the L3-L5 segments. A sagittal angle varied from 10° to 12°, without such definite relations. We conclude that the L1 and L2 segments display the most distinct morphometric similarities, while the greatest differences, in both genders, are noted for L3, L4, and L5. The findings enable the recommendation of the following screw diameters: 4 mm for L1-L2, 5 mm for L3, 6 mm for L4-L5, and the length of 50 mm. We believe the study has extended clinical knowledge on lumbar spine morphometry, essential in the training physicians engaged in transpedicular stabilization.
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http://dx.doi.org/10.1007/5584_2018_324DOI Listing
August 2019

ERCC1 assessment in upfront treatment with and without cisplatin-based chemotherapy in stage IIIB/IV non-squamous non-small cell lung cancer.

Med Oncol 2018 Jun 15;35(7):106. Epub 2018 Jun 15.

Department of Thoracic Oncology, University Hospital Heidelberg and Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Röntgenstr. 1, 69126, Heidelberg, Germany.

Prior studies have demonstrated an association between excision repair cross-complementation group 1 (ERCC1) expression level and outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with platinum-based chemotherapy. The aim of this study was to assess the impact of ERCC1 on survival for patients with stage IIIB/IV non-squamous NSCLC (NS-NSCLC) enrolled in the INNOVATIONS trial, thus receiving as treatment either erlotinib/bevacizumab (EB) or cisplatin/gemcitabine/bevacizumab (PGB). We retrospectively analyzed tumor tissue of 72 patients using immunohistochemistry to assess the expression of ERCC1. The distribution between treatment arms was equal (36 patients each). Two different H scores were calculated and correlated with survival. In ERCC1-positive patients, no significant difference in terms of progression-free survival (PFS) between treatment arms has been detected. ERCC1-negative patients benefited from PGB compared to EB arm (H score: HR = 0.377, 95% CI [0.167-0.849], p = 0.0151; modified H score: HR = 0.484, 95% CI [0.234-1.004], p = 0.0468). With respect to the scoring system, in the EB-arm, a significant superior PFS turned out in ERCC1-positive patients when employing the H-score (HR = 0.430, 95% CI [0.188-0.981], p = 0.0397; median 4.9 vs. 3.9 months), but not with the modified H-score. Our findings support the hypothesis that NS-NSCLC displaying a low ERCC1 expression might benefit from cisplatin-based chemotherapy. High expression indicated better PFS in the EB arm supporting the prognostic impact. However, as impact of ERCC1-assessment even might depend on scoring systems differences, the need in standardization of assessment methodology is emphasized.
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http://dx.doi.org/10.1007/s12032-018-1169-5DOI Listing
June 2018

Frequent expression of somatostatin receptor 2a in olfactory neuroblastomas: a new and distinctive feature.

Hum Pathol 2018 09 25;79:144-150. Epub 2018 May 25.

Department of Pathology, Technische Universität München, München, Germany.

Olfactory neuroblastoma (ONB) is a malignant neuroendocrine neoplasm with a usually slow course, but with considerable recurrence rate. Many neuroendocrine tumors have shown good response to the treatment with somatostatin analogs and somatostatin radioreceptor therapy. In ONBs, there are scarce data on somatostatin-based treatment and the cellular expression of somatostatin receptors (SSTR), the prerequisite for binding and effect of somatostatin on normal and tumor cells. The aim of our study was to investigate the immunohistochemical expression of SSTR2A and SSTR5 in a cohort of 40 ONBs. In addition, tissue microarrays containing 40 high-grade sinonasal carcinomas as well as 6 sinonasal lymphomas, 3 rhabdomyosarcomas, and 3 Ewing sarcomas were evaluated. Volante system was applied for staining evaluation. Thirty cases (75%) were immunopositive for SSTR2A and 3 (7.5%) for SSTR5. Among the 30 SSTR2A-positive ONBs, 19 tumors (63.3%) scored 2+ and 11 (36.7%) scored 3+. All SSTR5-positive ONBs scored 2+. Neither sinonasal carcinomas nor sinonasal small round blue cell neoplasms expressed SSTR2A or SSTR5. The frequent expression of SSTR2A provides a rationale for radioreceptor diagnosis and therapy with SST analogs in ONBs. SSTR2A expression in ONBs is a helpful adjunct in the differential diagnosis of ONBs.
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http://dx.doi.org/10.1016/j.humpath.2018.05.013DOI Listing
September 2018

Pitfalls in the management of bilateral adrenal enlargement.

Pol Arch Intern Med 2017 12 21;127(12):887-888. Epub 2017 Dec 21.

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http://dx.doi.org/10.20452/pamw.4175DOI Listing
December 2017

Expression of ALCAM (CD166) and PD-L1 (CD274) independently predicts shorter survival in malignant pleural mesothelioma.

Hum Pathol 2018 01 12;71:1-7. Epub 2017 Aug 12.

Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892.

Diffuse malignant mesothelioma of the pleura is a highly aggressive tumor typically associated with short survival. ALCAM (CD166), a type I transmembrane protein, is a member of the immunoglobulin superfamily. In normal cells, ALCAM regulates physiological processes such as angiogenesis and immune response. In cancer, it is associated with neoplastic progression, including invasion, migration, and metastasis. Furthermore, ALCAM is considered one of the cancer stem cell markers such as ALDH1 (ALDH1A1) and SALL4. The PD-L1 (CD274)/PD-1 (PDCD1, CD279) pathway is crucial for the modulation of immune responses in normal cells. Nevertheless, pathologic activation of the PD-L1/PD-1 pathway participates in immune evasion by tumor cells. Many PD-L1-expressing tumor cells have been identified in different types of cancer, including malignant mesothelioma. In this study, 175 well-characterized primary diffuse pleural mesotheliomas, including the epithelioid (n = 148), biphasic (n = 15), and sarcomatoid (n = 12) histotypes, were evaluated immunohistochemically for cancer stem cell markers (ALCAM, ALDH1, and SALL4) and PD-L1 expression. Twenty-five percent of the mesotheliomas (43/175) expressed ALCAM, whereas ALDH1 and SALL4 positivity was seen in 1% to 2% of cases. Thirty-three percent of the analyzed tumors (57/175) contained PD-L1-positive cells. Overall survival was significantly decreased in the cohort of patients with ALCAM- or PD-L1-positive tumors (both P < .01). Furthermore, the multivariate Cox hazards regression analysis identified ALCAM and PD-L1 (both P < 0.01) as potential independent risk factors. Thus, a combination of these 2 markers might be useful for prognostication and planning the treatment of patients with malignant pleural mesothelioma.
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http://dx.doi.org/10.1016/j.humpath.2017.04.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748003PMC
January 2018

Comprehensive immunohistochemical study of mesothelin (MSLN) using different monoclonal antibodies 5B2 and MN-1 in 1562 tumors with evaluation of its prognostic value in malignant pleural mesothelioma.

Oncotarget 2017 Apr;8(16):26744-26754

Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.

Mesothelin (MSLN) is a glycophosphatidylinositol (GPI)-linked cell surface protein highly expressed in several types of malignant tumors sometimes in association with increased tumor aggressiveness and poor clinical outcome. In the present study, 1562 tumors were immunohistochemically analyzed for mesothelin expression using two different types of mouse monoclonal antibodies (5B2 and MN-1) to determine the clinical usefulness of mesothelin immunohistochemistry as well as to pinpoint potential targets for future anti-mesothelin therapy. Also, characterization of selected mesothelin-positive tumors was performed by immunohistochemistry and oncogene sequencing. Among the tumors analyzed, the highest frequencies of mesothelin-positivity were detected in ovarian serous carcinoma (90% in 5B2 and 94% in MN-1). Both antibodies showed frequent positivity in pancreatic adenocarcinoma (71% using 5B2 and 87% using MN-1) and malignant pleural mesothelioma (75% using 5B2 and 78% using MN-1). In malignant mesothelioma, overall survival was significantly longer in the cohort of patients with diffuse membranous expression of mesothelin (P < 0.001). Both antibodies showed positive staining in thymic carcinoma (77% in 5B2 and 59% in MN-1), however, no expression was detected in thymoma. No correlation was detected between mesothelin expression and mismatch repair system deficient phenotype or gene mutation (BRAF and RAS) status in gastrointestinal adenocarcinomas. Mesothelin immunohistochemistry may assist the differential diagnosis of thymoma vs. thymic carcinoma as well as prognostication of mesothelioma patients. Our results demonstrate that patients with solid tumors expressing mesothelin could be targeted by anti-mesothelin therapies.
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http://dx.doi.org/10.18632/oncotarget.15814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5432294PMC
April 2017

Comment on "Diffuse TTF-1 expression in a case of Merkel cell carcinoma".

Pol J Pathol 2016 ;67(3):300

Department of Pathomorphology, Medical University of Gdansk, Gdansk, Poland.

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http://dx.doi.org/10.5114/pjp.2016.63784DOI Listing
July 2017

Keratin 7 expression in lymph node metastases but not in the primary tumour correlates with distant metastases and poor prognosis in colon carcinoma.

Pol J Pathol 2016;67(3):228-234

Department of Pathomorphology, Medical University of Gdańsk, Gdańsk, Poland.

Colorectal carcinoma (CRC) is one of the leading causes of cancer-related deaths worldwide. Alterations in keratin expression, including keratin 7 (K7), are frequent findings in multiple cancers, and they constitute a prognostic factor. The aim of our study was to evaluate the prognostic significance of K7 in the primary tumour and lymph node metastases in two separate cohorts of patients: the first one with lymph node involvement (LN+, 129 cases) and the second one free of LN metastases (LN-, 85 cases). Keratin 7 expression in CRC was analysed on tissue microarrays with immunohistochemistry and evaluated using the h-score. In the LN+ group K7 positivity was identified in 7/129 (5.4%) of primary tumours (PT) and lymph node metastases (LNM); concordance between them was 94% ( 0.396). Keratin 7 was expressed in 8/85 cases (9.4%) in the LN- group. K7 expression in LNM of the LN+ cohort correlated with shorter overall survival (OS) (p = 0.047) and presence of distant metastases at diagnosis (p = 0.005). Expression of K7 in the primary tumour in both cohorts did not correlate with survival. We conclude that the status of K7 expression in metastatic lymph nodes from CRC is a poor prognostic factor.
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http://dx.doi.org/10.5114/pjp.2016.63774DOI Listing
June 2017

Fluorescent Versus Radioguided Lymph Node Mapping in Bladder Cancer.

Clin Genitourin Cancer 2017 06 30;15(3):e405-e409. Epub 2016 Nov 30.

Urology Department, Medical University of Gdańsk, Gdańsk, Poland.

Introduction: The aim of the study was to compare 2 methods of the sentinel lymph node biopsy (SLNB) procedure in bladder cancer: we applied technetium radiocolloid (RadCol) detected by a gamma ray detection probe, and indocyanine green (ICG) detected by a near-infrared fluorescent (NIRF) camera.

Material And Methods: The SLNB was performed on 50 patients using the RadCol and the ICG, followed by a lymphadenectomy and a pathologic examination.

Results: In the analyzed group of 47 patients (3 patients were excluded owing to the lack of lymphatic drainage from the tumor), the SLNB was performed using the 2 methods. The ICG with a NIRF-guided camera detected all sentinel lymph nodes (SLNs) in 46 cases, whereas RadCol detected them in 45 cases. In 12 (25.6%) of 47 patients, the ICG-fluorescent method revealed more SLNs than the RadCol method. In 8 (17%) patients, the SLNs revealed in the ICG fluorescence were metastatic. In 3 (6.4%) patients, we found SLNs outside the standard lymphadenectomy template, but a histopathologic examination showed they were negative for cancer. In 3 (6.4%) patients, the SLNs detected by both methods were negative for cancer, but other resected lymph nodes revealed metastases.

Conclusion: Our study shows that SLNB procedure with the RadCol or the ICG method is useful for the evaluation of lymph nodes in bladder cancer. The new ICG fluorescent technique with a NIRF camera system is safe, enables live view of the results of the procedure, and does not create additional costs. However, it highlights more lymph nodes than the radioactive method.
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http://dx.doi.org/10.1016/j.clgc.2016.11.007DOI Listing
June 2017

PD-L1 Expression by Two Complementary Diagnostic Assays and mRNA In Situ Hybridization in Small Cell Lung Cancer.

J Thorac Oncol 2017 01 14;12(1):110-120. Epub 2016 Sep 14.

Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado. Electronic address:

Introduction: Therapeutic antibodies to immune checkpoints show promising results. Programmed death-ligand 1 (PD-L1), an immune checkpoint ligand, blocks the cancer immunity cycle by binding the PD-L1 receptor (programmed death 1). We investigated PD-L1 protein expression and messenger RNA (mRNA) levels in SCLC.

Methods: PD-L1 protein expression and mRNA levels were determined by immunohistochemistry (IHC) with SP142 and Dako 28-8 PD-L1 antibodies and in situ hybridization in primary tumor tissue microarrays in both tumor cells and tumor-infiltrating immune cells (TIICs) obtained from a limited-disease SCLC cohort of 98 patients. An additional cohort of 96 tumor specimens from patients with extensive-disease SCLC was assessed for PD-L1 protein expression in tumor cells with Dako 28-8 antibody only.

Results: The overall prevalence of PD-L1 protein expression in tumor cells was 16.5%. In the limited-disease cohort, the prevalences of PD-L1 protein expression in tumor cells with SP142 and Dako 28-8 were 14.7% and 19.4% (tumor proportion score cutoff ≥1%) and PD-L1 mRNA ISH expression was positive in 15.5% of tumor samples. Increased PD-L1 protein/mRNA expression was associated with the presence of more TIICs (p < 0.05). The extensive-disease cohort demonstrated a 14.9% positivity of PD-L1 protein expression in tumor cells with Dako 28-8 antibody.

Conclusions: A subset of SCLCs is characterized by positive PD-L1 and/or mRNA expression in tumor cells. Higher PD-L1 and mRNA expression correlate with more infiltration of TIICs. The prevalence of PD-L1 in SCLC is lower than that published for NSCLC. The predictive role of PD-L1 expression in SCLC treatment remains to be established.
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http://dx.doi.org/10.1016/j.jtho.2016.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5353355PMC
January 2017

Expression of SOX11, PAX5, TTF-1 and ISL-1 in medulloblastoma.

Pathol Res Pract 2016 Nov 11;212(11):965-971. Epub 2016 Aug 11.

Department of Pathomorphology, Medical University of Gdansk, Poland.

The aim of our study was to evaluate the immunohistochemical expression of SOX11, PAX5, TTF-1 and ISL-1 in medulloblastoma (MB) to investigate their diagnostic usefulness.

Methods: Immunohistochemical expression of PAX5 (two antibodies: Dako, DAK-Pax5; and BD, clone 24), TTF-1 (Dako, 8G7G3/1), SOX11 (CL0142; Abcam) and ISL-1 (1 H9, Abcam) was analyzed using the h-score and Remmele score in 25 cases of MB.

Results: There were 18 MBs of classic and 7 of desmoplastic type. SOX11 was strongly expressed in all tumors. The expression of PAX5 was higher and more frequent in a case of DAK-Pax5 clone (25/25) than clone 24 (6/25). ISL-1 was positive in 11 (44%) and TTF-1 in 3 (12%) cases. ISL-1 expression correlated positively (p<0.001), while TTF-1 correlated negatively with the age of patients (p=0.039). PAX5 expression correlated with ISL-1 (p=0.039) and showed a trend toward higher expression in the desmoplastic subtype (p=0.069).

Conclusions: SOX11 is strongly and robustly expressed in MBs. PAX5 expression pattern differs substantially among two antibody clones. TTF-1 and ISL-1 is associated with the age of patients.
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http://dx.doi.org/10.1016/j.prp.2016.08.006DOI Listing
November 2016

Prognostic value of 5-microRNA based signature in T2-T3N0 colon cancer.

Clin Exp Metastasis 2016 12 2;33(8):765-773. Epub 2016 Aug 2.

Department of Oncology and Radiotherapy, Medical University of Gdansk, 7 Dębinki St., 80-211, Gdańsk, Poland.

The role of adjuvant chemotherapy in stage T2-T3N0 colon cancer (CC) is controversial and there are currently no reliable factors allowing for individual selection of patients with high risk of relapse for such therapy. We searched for microRNA-based signature with prognostic significance in this group. We assessed by qRT-PCR expression of 754 microRNAs (miRNAs) in tumour samples from 85 stage pT2-3N0 CC patients treated with surgery alone. MiRNA expression was compared between two groups of patients: 40 and 45 patients who did and did not develop distant metastases after resection, respectively. Additionally, miRNA expression was compared between CC and normal colon mucosa samples and between the mismatch repair (MMR) competent and deficient tumours. Low expression of miR-1300 and miR-939 was significantly correlated with shorter distant metastasis-free survival (DMFS) in Cox univariate analysis (p.adjusted = 0.049). The expression signature of five miRNAs (miR-1296, miR-135b, miR-539, miR-572 and miR-185) was found to be prognostic [p = 1.28E-07, HR 8.4 (95 % CI: 3.81-18.52)] for DMFS and cross-validated in a leave-one-out analysis, with the sensitivity and specificity of 74 and 78 %, respectively. The expression of miR-592 was significantly associated with the MMR status (p.adjusted <0.01). The expression of several novel miRNAs were found to be tumour specific, e.g. miR-888, miR-523, miR-18b, miR-302a, miR-423-5p, miR-582-3p (p < 0.05). We developed a miRNA expression signature that may be predictive for the risk of distant relapse in early stage CC and confirmed previously reported association between miR-592 expression and MMR status.
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http://dx.doi.org/10.1007/s10585-016-9810-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5110606PMC
December 2016

TTF-1 and PAX5 Are Frequently Expressed in Combined Merkel Cell Carcinoma.

Am J Dermatopathol 2016 Jul;38(7):513-6

*Department of Pathomorphology, Medical University of Gdansk, Gdansk, Poland; †Dermatopathologie Friedrichshafen, Friedrichshafen, Germany; ‡Sikl's Department of Pathology, Charles University Medical Faculty Hospital Alej Svobody, Pilsen, Czech Republic; and §Department of Plastic Surgery, Medical University of Gdansk, Gdansk, Poland.

Thyroid transcription factor-1 (TTF-1) is a marker of tumors of pulmonary and thyroid origin, and its expression practically excludes diagnosis of Merkel cell carcinoma (MCC). However, TTF-1 expression in combined MCC was recently reported. PAX5 is a marker of B-cell origin that is also expressed in most classical MCC cases; however, its expression was not described in combined MCC. The authors decided to evaluate the expression of both these markers in a group of 5 combined MCCs (2 with invasive squamous cell carcinoma, 2 with squamous cell carcinoma in situ, and 1 with basal cell carcinoma). Expression of TTF-1 was found in 4 of 5 cases; in 3 cases, the marker was shown in the MCC component (weakly in 2 cases and strongly in 1 case), whereas the non-MCC component presented TTF-1 expression in 2 cases. A weak-to-moderate immunoreactivity for PAX5 was identified in all cases of the MCC component but in none of the non-MCC component. The results show that the expression of TTF-1 is a frequent finding in combined MCC and can be present in the neuroendocrine component, which differs from the conventional MCC. In contrast, PAX5 expression pattern is similar to that of the classical MCC.
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http://dx.doi.org/10.1097/DAD.0000000000000464DOI Listing
July 2016

Genetic and molecular alterations in olfactory neuroblastoma: implications for pathogenesis, prognosis and treatment.

Oncotarget 2016 Aug;7(32):52584-52596

Department of Neuropathology, Institute of Pathology, Medical University of Graz, Graz, Austria.

Olfactory neuroblastoma (ONB, Esthesioneuroblastoma) is an infrequent neoplasm of the head and neck area derived from olfactory neuroepithelium. Despite relatively good prognosis a subset of patients shows recurrence, progression and/or metastatic disease, which requires additional treatment. However, neither prognostic nor predictive factors are well specified. Thus, we performed a literature search for the currently available data on disturbances in molecular pathways, cytogenetic changes and results gained by next generation sequencing (NGS) approaches in ONB in order to gain an overview of genetic alterations which might be useful for treating patients with ONB. We present briefly ONB molecular pathogenesis and propose potential therapeutic targets and prognostic factors. Possible therapeutic targets in ONB include: receptor tyrosine kinases (c-kit, PDGFR-b, TrkB; EGFR); somatostatin receptor; FGF-FGFR1 signaling; Sonic hedgehog pathway; apoptosis-related pathways (Bcl-2, TRAIL) and neoangiogenesis (VEGF; KDR). Furthermore, we compare high- and low-grade ONB, and describe its frequent mimicker: sinonasal neuroendocrine carcinoma. ONB is often a therapeutic challenge, so our goal should be the implementation of acquired knowledge into clinical practice, especially at pretreated, recurrent and metastatic stages. Moreover, the multicenter molecular studies are needed to increase the amount of available data.
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http://dx.doi.org/10.18632/oncotarget.9683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5239575PMC
August 2016

CD99 correlates with low cyclin D1, high topoisomerase 2 status and triple negative molecular phenotype but is prognostically irrelevant in breast carcinoma.

Pol J Pathol 2015 Sep;66(3):269-75

Piotr Czapiewski, Department of Pathology, Medical University of Gdansk, Debinki 7, 80-952 Gdansk, Poland, tel. +48 58 349 37 42, fax +48 58 349 37 50, e-mail:

CD99 is a protein initially described in the Ewing sarcoma family of tumors, but growing evidence has shown its expression in other tumors of mesenchymal, hematopoietic and even epithelial origin. Some articles report CD99 in metaplastic carcinoma of the breast, a subtype of breast carcinoma (BC) with pronounced epithelial to mesenchymal (EMT) phenotype. Our aim was to analyse the potential relationship between CD99 and selected EMT (vimentin, E-cadherin, Twist) and proliferation markers (Ki-67, c-myc, cyclin D1, topoisomerase 2), molecular subtypes of BC, as well as overall survival (OS) and progression-free survival (PFS). In a group of 122 cases CD99 membrane expression was seen in 14 (11.5%) cases: strong in 11 (9%) and moderate in 3 (2.5%). Expression of CD99 correlated with low cyclin D1 index, high level of topoisomerase 2 expression and lack of progesterone receptor (PR) but not with EMT characteristics. Additionally, strong expression of CD99 correlated with triple negative molecular BC phenotype. CD99 was prognostically irrelevant for OS and PFS. CD99 correlates with selected proliferative markers and low ER/PR receptor status but not with patients' outcome in BC. Further studies are required to explain precisely its role in molecular pathogenesis of BC.
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http://dx.doi.org/10.5114/pjp.2015.54961DOI Listing
September 2015

Renal cell carcinoma metastases to the pancreas and the thyroid gland 19 years after the primary tumour.

Prz Gastroenterol 2015 10;10(3):185-9. Epub 2015 Feb 10.

Department of General, Endocrine and Transplant Surgery, Medical University of Gdansk, Gdansk, Poland.

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http://dx.doi.org/10.5114/pg.2015.49000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4607689PMC
October 2015

A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo.

Sci Transl Med 2015 Aug;7(302):302ra136

Stemcentrx Inc., South San Francisco, CA 94080, USA.

The high-grade pulmonary neuroendocrine tumors, small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC), remain among the most deadly malignancies. Therapies that effectively target and kill tumor-initiating cells (TICs) in these cancers should translate to improved patient survival. Patient-derived xenograft (PDX) tumors serve as excellent models to study tumor biology and characterize TICs. Increased expression of delta-like 3 (DLL3) was discovered in SCLC and LCNEC PDX tumors and confirmed in primary SCLC and LCNEC tumors. DLL3 protein is expressed on the surface of tumor cells but not in normal adult tissues. A DLL3-targeted antibody-drug conjugate (ADC), SC16LD6.5, comprised of a humanized anti-DLL3 monoclonal antibody conjugated to a DNA-damaging pyrrolobenzodiazepine (PBD) dimer toxin, induced durable tumor regression in vivo across multiple PDX models. Serial transplantation experiments executed with limiting dilutions of cells provided functional evidence confirming that the lack of tumor recurrence after SC16LD6.5 exposure resulted from effective targeting of DLL3-expressing TICs. In vivo efficacy correlated with DLL3 expression, and responses were observed in PDX models initiated from patients with both limited and extensive-stage disease and were independent of their sensitivity to standard-of-care chemotherapy regimens. SC16LD6.5 effectively targets and eradicates DLL3-expressing TICs in SCLC and LCNEC PDX tumors and is a promising first-in-class ADC for the treatment of high-grade pulmonary neuroendocrine tumors.
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http://dx.doi.org/10.1126/scitranslmed.aac9459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4934375PMC
August 2015

Comparison of Real-Time Fluorescent Indocyanine Green and (99m)Tc-Nanocolloid Radiotracer Navigation in Sentinel Lymph Node Biopsy of Penile Cancer.

Clin Genitourin Cancer 2015 Dec 2;13(6):574-80. Epub 2015 Jul 2.

Urology Department, Medical University of Gdansk, Gdansk, Poland.

Introduction: The aim of this study was to compare lymphatic drainage patterns detected with fluorescent dye indocyanine green (ICG) with the lymphatic drainage patterns detected with radiotracer (99m)Tc-nanocolloid in dynamic sentinel node biopsy (DSNB) procedures.

Patients And Methods: Fourteen patients with penile cancer and no palpable lymph nodes were included prospectively for DSNB. First, on the day of surgery (99m)Tc-nanocolloid was injected at the lesion site. Then, single photon emission computed tomography (SPECT) lymphoscintigraphy was performed. ICG was injected in the same manner as the radiotracer just before the surgery. In all cases partial penectomy and DSNB were performed. Sentinel lymph nodes (SLNs) were localized intraoperatively using the gamma-ray detection probe for radiocolloid and near infrared fluorescence (NIRF) camera for ICG.

Results: Transcutaneously, lymphatic nodes were identified in all 14 patients using the gamma probe and in 10 patients using the NIRF camera. After skin incision, fluorescent nodes were observed using the NIRF camera in the remaining 4 patients. The examination led to identification of 32 SLNs in total using technetium and ICG and additionally 3 more nodes visible only using ICG. All SLNs found using SPECT were also fluorescent. In 3 patients ICG enabled only approximate localization of the SLNs. Of 35 SLNs, 30 were negative and 4 were positive for metastasis.

Conclusion: Our analysis of the effectiveness of ICG compared with radiocolloid in the DSNB for penile cancer indicates that they are comparable with some specific advantages and disadvantages. These findings must be studied further in a larger group of patients.
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http://dx.doi.org/10.1016/j.clgc.2015.06.005DOI Listing
December 2015

Paraneoplastic syndromes in olfactory neuroblastoma.

Contemp Oncol (Pozn) 2015 26;19(1):6-16. Epub 2015 Mar 26.

Department of Endocrinology and Internal Diseases, Medical University of Gdańsk, Poland.

Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of sinonasal tract, derived from olfactory epithelium. Unilateral nasal obstruction, epistaxis, sinusitis, and headaches are common symptoms. Olfactory neuroblastoma shows neuroendocrine differentiation and similarly to other neuroendocrine tumors can produce several types of peptic substances and hormones. Excess production of these substances can be responsible for different types of endocrinological paraneoplastic syndromes (PNS). Moreover, besides endocrinological, in ONB may also occur neurological PNS, caused by immune cross-reactivity between tumor and normal host tissues in the nervous system. Paraneoplastic syndromes in ONB include: syndrome of inappropriate ADH secretion (SIADH), ectopic ACTH syndrome (EAS), humoral hypercalcemia of malignancy (HHM), hypertension due to catecholamine secretion by tumor, opsoclonus-myoclonus-ataxia (OMA) and paraneoplastic cerebellar degeneration. Paraneoplastic syndromes in ONB tend to have atypical features, therefore diagnosis may be difficult. In this review, we described initial symptoms, patterns of presentation, treatment and outcome of paraneoplastic syndromes in ONB, reported in the literature.
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http://dx.doi.org/10.5114/wo.2015.46283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4507891PMC
July 2015

Sox10--a marker for not only schwannian and melanocytic neoplasms but also myoepithelial cell tumors of soft tissue: a systematic analysis of 5134 tumors.

Am J Surg Pathol 2015 Jun;39(6):826-35

*Laboratory of Pathology, NCI/NIH, Bethesda #Joint Pathology Center of the Capital Region, Silver Spring, MD †Department of Pathology, Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA ¶Southern California Permanente Medical Group, Woodland Hills, CA ‡University of Helsinki and HUSLab/Pathology, Helsinki, Finland §Department of Pathology, Medical University of Gdansk, Gdansk ∥Holy Cross Cancer Center, Kielce, Poland.

Sox10 transcription factor is expressed in schwannian and melanocytic lineages and is important in their development and can be used as a marker for corresponding tumors. In addition, it has been reported in subsets of myoepithelial/basal cell epithelial neoplasms, but its expression remains incompletely characterized. In this study, we examined Sox10 expression in 5134 human neoplasms spanning a wide spectrum of neuroectodermal, mesenchymal, lymphoid, and epithelial tumors. A new rabbit monoclonal antibody (clone EP268) and Leica Bond Max automation were used on multitumor block libraries containing 30 to 70 cases per slide. Sox10 was consistently expressed in benign Schwann cell tumors of soft tissue and the gastrointestinal tract and in metastatic melanoma and was variably present in malignant peripheral nerve sheath tumors. In contrast, Sox10 was absent in many potential mimics of nerve sheath tumors such as cellular neurothekeoma, meningioma, gastrointestinal stromal tumors, perivascular epithelioid cell tumor and a variety of fibroblastic-myofibroblastic tumors. Sox10 was virtually absent in mesenchymal tumors but occasionally seen in alveolar rhabdomyosarcoma. In epithelial tumors of soft tissue, Sox10 was expressed only in myoepitheliomas, although often absent in malignant variants. Carcinomas, other than basal cell-type breast cancers, were only rarely positive but included 6% of squamous carcinomas of head and neck and 7% of pulmonary small cell carcinomas. Furthermore, Sox10 was often focally expressed in embryonal carcinoma reflecting a primitive Sox10-positive phenotype or neuroectodermal differentiation. Expression of Sox10 in entrapped non-neoplastic Schwann cells or melanocytes in various neoplasms has to be considered in diagnosing Sox10-positive tumors. The Sox10 antibody belongs in a modern immunohistochemical panel for the diagnosis of soft tissue and epithelial tumors.
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http://dx.doi.org/10.1097/PAS.0000000000000398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431945PMC
June 2015