Publications by authors named "Roman Kodet"

82 Publications

Giant lung metastasis of NRAS-mutant melanoma in a 24-year-old patient with a history of BRAF-mutant conventional melanoma harboring Spitzoid morphology: a case report.

Diagn Pathol 2020 Oct 25;15(1):132. Epub 2020 Oct 25.

Third Department of Surgery, First Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.

Background: Spitzoid melanocytic lesions represent a heterogeneous group of proliferations with ambiguous and overlapping terminology. The exact distinction of a Spitz nevus from a Spitzoid melanoma can be very difficult or, in some cases, impossible. Among the Spitzoid lesions, there is a lesion termed an atypical Spitz tumour (AST) that has intermediate histopathologic features between those of a Spitz nevus and a Spitzoid melanoma and thus uncertain malignant potential. There are several rare cases of patients with a Spitzoid melanoma initially misdiagnosed as a Spitz nevus or an AST with fatal consequences. It is, therefore, advised to perform a molecular characterization in cases where uncertain skin lesions are presented, as it may provide extended set of information with a possible impact on the treatment options. Furthermore, preventive measures, such as regular physical and skin examinations, as well as thorough scheduling of individual follow-up visits, are essential in patients with potentially malignant skin nevi.

Case Report: We report a case of a young adult female with a history of AST excision with a negative sentinel lymph node biopsy (SLNB) and insufficient follow-up. Four years after the primary dermatological diagnosis, she presented with a giant tumour in the right hemithorax. Radical en bloc resection of the tumour with right pneumonectomy and resection of the pericardium with reconstruction of the pericardium using mesh was performed. A definitive histopathological examination revealed a metastatic melanoma. The association of the previously diagnosed AST and subsequent appearance of melanoma metastases led to a retrospective re-evaluation of the initial lesion. The suspected diagnosis of Spitzoid melanoma, however, was not confirmed. Moreover, the molecular examination revealed a major discordance between the initial lesion and the lung tumour, which most likely excluded the possible association of the lung metastasis with the initial skin lesion. The initial skin lesion was a BRAF-mutant melanoma with Spitzoid features and termed as AST, while the giant lung metastasis was NRAS-mutant melanoma. The subsequent postoperative course was complicated by the appearance of brain metastases that were stereotactically irradiated. Nevertheless, despite complex specialised medical care, the patient's clinical condition rapidly deteriorated. By this time, no active oncological treatment was possible. The patient was delegated to local hospice for palliative care six months after the surgery and died three weeks later.

Conclusions: Our patient was surgically treated at the age of 20 for AST and died four years later of metastatic NRAS-mutant melanoma most likely of different occult origin. Molecular characterization, as well as the close clinical follow-up should be always precisely performed in patients with uncertain skin lesions, such as AST.
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http://dx.doi.org/10.1186/s13000-020-01046-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586673PMC
October 2020

Gastric tumors in children: single-center study with emphasis on treatment of repeated recurrence.

Pediatr Surg Int 2020 Aug 19;36(8):917-924. Epub 2020 Jun 19.

Department of Pediatric Surgery, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic.

Purpose: Analysis of surgical management and survival of pediatric patients with gastric tumors treated at our institution.

Methods: A retrospective study of patients with primary gastric tumors treated between 1993 and 2018 was conducted.

Results: Eight patients, five girls and three boys, were diagnosed with gastric tumors at an average age of 10.4 years (1 day-15.4 years). Surgical management included Billroth type I procedure in five and tumor excision in three patients. Histology revealed gastrointestinal stromal tumor (GIST) in four patients and one of each of schwannoma, myofibroblastic tumor, hamartoma and teratoma. Microscopically clear margins were reported in six patients. Repeated local recurrence occurred in three patients (2 × GIST, 1 × myofibroblastic tumors) who consequently underwent three, four and six reoperations. One of these patients had liver metastases, which were managed with ligation of the hepatic arteries. This patient was also diagnosed with a lung hamartoma, which was treated with a lobectomy. Survival rate was 100% with a median follow-up of 8.6 years (7 months-25.5 years).

Conclusions: Gastric tumors are rare in children and represent a management challenge. Repeated recurrence of GISTs and myofibroblastic tumors remains frequent even after complete resection and may necessitate multiple surgeries, therefore patients require a lifelong follow-up.
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http://dx.doi.org/10.1007/s00383-020-04698-wDOI Listing
August 2020

Analysis of HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinomas and Paired Normal Mucosae Reveals Cyclin D1 Deregulation and Compensatory Effect of Cyclin D2.

Cancers (Basel) 2020 03 26;12(4). Epub 2020 Mar 26.

Institute of Microbiology of the Czech Academy of Sciences, 142 00 Prague, Czech Republic.

Aberrant regulation of the cell cycle is a typical feature of all forms of cancer. In head and neck squamous cell carcinoma (HNSCC), it is often associated with the overexpression of cyclin D1 (). However, it remains unclear how expression changes between tumor and normal tissues and whether human papillomavirus (HPV) affects differential expression. Here, we evaluated the expression of D-type cyclins in a cohort of 94 HNSCC patients of which 82 were subjected to whole genome expression profiling of primary tumors and paired normal mucosa. Comparative analysis of paired samples showed that was upregulated in 18% of HNSCC tumors. Counterintuitively, was downregulated in 23% of carcinomas, more frequently in HPV-positive samples. There was no correlation between the change in D-type cyclin expression and patient survival. Intriguingly, among the tumors with downregulated , one-third showed an increase in cyclin D2 () expression. On the other hand, one-third of tumors with upregulated showed a decrease in . Collectively, we have shown that was frequently downregulated in HNSCC tumors. Furthermore, regardless of the HPV status, our data suggested that a change in expression was alleviated by a compensatory change in expression.
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http://dx.doi.org/10.3390/cancers12040792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226528PMC
March 2020

Gastrointestinal stromal tumors - Summary of mutational status of the primary/secondary KIT/PDGFRA mutations, BRAF mutations and SDH defects.

Pathol Res Pract 2019 Dec 29;215(12):152708. Epub 2019 Oct 29.

Department of Pathology and Molecular Medicine, Charles University - 2nd Faculty of Medicine and Faculty Hospital Motol, Czech Republic.

The most important findings revealing pathogenesis, molecular characteristics, genotyping and targeted therapy of gastrointestinal stromal tumors (GISTs) are activated oncogenic mutations in KIT and PDGFRA genes. Imatinib mesylate (IM), which inhibits both KIT and PDGFRA receptors, significantly improved treatment of advanced (metastatic, recurrent, and/or inoperable) GISTs. However, in a significant number of patients the treatment fails due to the primary or secondary resistance to targeted therapy. Most common cause of secondary resistance is a presence of secondary mutations. Approximately 15% of adult patients with GISTs are negative for mutations in KIT or PDGFRA genes. These so-called wild-type GISTs appear to be characterized by other oncogenetic drivers, including mutations in BRAF, RAS, NF1 genes, and subunits of succinate dehydrogenase (SDH) complex. In the present study we investigated 261 tumour specimens from 239 patients with GIST. Primary mutations were detected in 82 % tumor specimens. 66 of them were in KIT, and 16 % in PDGFRA genes. Remaining 18 % were KIT/PDGFRA wild-type. Secondary KIT mutations were detected in 10 from 133 (7 %) patients treated with IM. We examined secondary KIT mutations in exons 13 and 17 and secondary PDGFRA mutation in exon 18 in sixteen progressive tumors and/or metastasis (from overall 22 samples). We identified BRAF V600E point mutation in 4 % of KIT/PDGFRA wild-type GIST patients. Moreover, we analysed SDH complex mutations in 4 younger patients (15, 33, 37, and 45 years old) from 44 patients without KIT, PDGFRA, and BRAF mutations. Two patients (a 37-year old man, and a 33-year old woman) had defects of the SDH complex. Our findings of mutational status of the primary and secondary KIT/PDGFRA mutations in patients with GIST confirm mechanisms of primary and secondary resistance, and also intralesional and interlesional heterogeneity of secondary mutations within and between progressive lesions. Moreover, detection of V600E BRAF mutation and defects of SDH complex in KIT/PDGFRA wild-type GISTs confirm their activation and allow for a selection of targeted therapy.
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http://dx.doi.org/10.1016/j.prp.2019.152708DOI Listing
December 2019

Development of high‑resolution melting analysis for ABCB1 promoter methylation: Clinical consequences in breast and ovarian carcinoma.

Oncol Rep 2019 Aug 5;42(2):763-774. Epub 2019 Jun 5.

Toxicogenomics Unit, Centre of Toxicology and Health Safety, National Institute of Public Health, 10042 Prague, Czech Republic.

Multidrug resistance to anticancer drugs, which is often associated with enhanced expression of the ATP‑binding cassette (ABC) transporter P‑glycoprotein (encoded by the ABCB1 gene) may limit the effects of cancer therapy. Epigenetic regulation of ABCB1 expression may thus have a clinical impact. A detailed assessment of ABCB1 promoter methylation is of importance for predicting therapy outcome and prognosis. Thus, validated methods for the analysis of ABCB1 promoter methylation are urgently required. In the present study, high‑resolution melting (HRM) analysis of the CpG island regions covering the distal promoter of the ABCB1 gene was developed and compared with pyrosequencing. In addition, the clinical effects of the methylation status of the ABCB1 promoter were analyzed in patients with breast and ovarian carcinoma prior and subsequent to chemotherapy treatment. HRM analysis of ABCB1 methylation correlated with the results of pyrosequencing (P=0.001) demonstrating its analytical validity and utility. Hypermethylation of the analyzed ABCB1 promoter region was significantly correlated with low levels of the ABCB1 transcript in tumors from a subset of patients with breast and ovarian carcinoma prior to chemotherapy but not following treatment. Finally, high ABCB1 transcript levels were observed in tumors of patients with short progression‑free survival prior to chemotherapy. Our data suggest the existence of functional epigenetic changes in the ABCB1 gene with prognostic value in tumor tissues of patients with breast and ovarian carcinoma. The clinical importance of such changes should be further evaluated.
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http://dx.doi.org/10.3892/or.2019.7186DOI Listing
August 2019

TIM-3 Dictates Functional Orientation of the Immune Infiltrate in Ovarian Cancer.

Clin Cancer Res 2019 08 10;25(15):4820-4831. Epub 2019 May 10.

Department of Immunology, Charles University, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.

Purpose: In multiple oncological settings, expression of the coinhibitory ligand PD-L1 by malignant cells and tumor infiltration by immune cells expressing coinhibitory receptors such as PD-1, CTLA4, LAG-3, or TIM-3 conveys prognostic or predictive information. Conversely, the impact of these features of the tumor microenvironment on disease outcome among high-grade serous carcinoma (HGSC) patients remains controversial.

Experimental Design: We harnessed a retrospective cohort of 80 chemotherapy-naïve HGSC patients to investigate PD-L1 expression and tumor infiltration by CD8 T cells, CD20 B cells, DC-LAMP dendritic cells as well as by PD-1, CTLA4, LAG-3, and TIM-3 cells in relation with prognosis and function orientation of the tumor microenvironment. IHC data were complemented with transcriptomic and functional studies on a second prospective cohort of freshly resected HGSC samples. analysis of publicly available RNA expression data from 308 HGSC samples was used as a confirmatory approach.

Results: High levels of PD-L1 and high densities of PD-1 cells in the microenvironment of HGSCs were strongly associated with an immune contexture characterized by a robust T1 polarization and cytotoxic orientation that enabled superior clinical benefits. Moreover, PD-1TIM-3CD8 T cells presented all features of functional exhaustion and correlated with poor disease outcome. However, although PD-L1 levels and tumor infiltration by TIM-3 cells improved patient stratification based on the intratumoral abundance of CD8 T cells, the amount of PD-1 cells failed to do so.

Conclusions: Our data indicate that PD-L1 and TIM-3 constitute prognostically relevant biomarkers of active and suppressed immune responses against HGSC, respectively.
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http://dx.doi.org/10.1158/1078-0432.CCR-18-4175DOI Listing
August 2019

Mature dendritic cells correlate with favorable immune infiltrate and improved prognosis in ovarian carcinoma patients.

J Immunother Cancer 2018 12 4;6(1):139. Epub 2018 Dec 4.

Department of Immunology, Charles University, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.

A high density of tumor-infiltrating CD8 T cells and CD20 B cells correlates with prolonged survival in patients with a wide variety of human cancers, including high-grade serous ovarian carcinoma (HGSC). However, the potential impact of mature dendritic cells (DCs) in shaping the immune contexture of HGSC, their role in the establishment of T cell-dependent antitumor immunity, and their potential prognostic value for HGSC patients remain unclear. We harnessed immunohistochemical tests and biomolecular analyses to demonstrate that a high density of tumor-infiltrating DC-LAMP DCs is robustly associated with an immune contexture characterized by T1 polarization and cytotoxic activity. We showed that both mature DCs and CD20 B cells play a critical role in the generation of a clinically-favorable cytotoxic immune response in HGSC microenvironment. In line with this notion, robust tumor infiltration by both DC-LAMP DCs and CD20 B cells was associated with most favorable overall survival in two independent cohorts of chemotherapy-naïve HGSC patients. Our findings suggest that the presence of mature, DC-LAMP DCs in the tumor microenvironment may represent a novel, powerful prognostic biomarker for HGSC patients that reflects the activation of clinically-relevant anticancer immunity.
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http://dx.doi.org/10.1186/s40425-018-0446-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288908PMC
December 2018

Indications and outcomes of duodenum-preserving resection of the pancreatic head in children.

Pediatr Surg Int 2019 Apr 1;35(4):449-455. Epub 2018 Nov 1.

Department of Surgery, University Hospital Kralovske Vinohrady, Prague, Czech Republic.

Aim Of Study: Duodenum-preserving resection of the pancreatic head (DPRPH) with Roux-en-Y pancreatojejunostomy is a procedure used to remove focal pathological lesions of the pancreatic head. Although predominantly used in adult patients, it is both safe and effective in children. The aim of this study was to review our experience with this procedure, with focus on its indications, complications and long-term outcomes.

Methods: A retrospective analysis of pediatric patients who underwent DPRPH between 1994 and 2015 was performed. Patient files were reviewed for demographic, diagnostic, operative and histological details, postoperative complications. Patients were contacted telephonically and sent questionnaires to determine long-term outcomes.

Results: The study cohort consists of 21 patients, 14 girls and 7 boys, with an average age of 11.72 years (range 3 months to 18.6 years), who underwent DPRPH with end-to-end anastomosis of the jejunum to the pancreatic body (Roux-en-Y anastomosis). In four cases the head and also part of the body of the pancreas was resected. In the remaining 17 cases, only the head of the pancreas was resected. Indications for DPRPH were solid pseudopapillary tumor of the pancreas (n = 10), trauma (n = 8), pancreas divisum (n = 1), focal congenital hyperinsulinism (n = 1) and pancreatic cyst (n = 1). The length of follow-up ranged from 1 to 22 years (average 9.66). One patient developed a biliary fistula, which closed spontaneously within 2 weeks after stent insertion. A recurrence of abdominal pain was reported in two patients, occurring at 7 months after the operation in one patient and at 1 year in the other. Pancreatic endocrine insufficiency did not occur in any of the 21 patients. Seven patients currently require a low fat diet, five of which need pancreatic enzyme supplementation. An additional two patients need enzyme supplementation without dietary restriction.

Conclusion: DPRPH is a safe and effective procedure for the treatment of large focal pathological lesions of the pancreatic head in children. As a less invasive procedure than pancreatoduodenectomy, it is more appropriate for the developing child.
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http://dx.doi.org/10.1007/s00383-018-4410-6DOI Listing
April 2019

Potential loss of prognostic significance of minimal residual disease assessment after R-CHOP-based induction in elderly patients with mantle cell lymphoma in the era of rituximab maintenance.

Hematol Oncol 2018 Dec 13;36(5):773-778. Epub 2018 Sep 13.

First Medical Department, Charles University General Hospital in Prague, Czech Republic.

Rituximab maintenance (RM) prolongs survival of elderly patients with mantle cell lymphoma (MCL). Persistent minimal residual disease (MRD) after induction repeatedly correlated with shorter progression-free survival (PFS). However, none of the published studies analyzed patients treated with RM. The main purpose was to analyze prognostic significance of MRD in the elderly patients with newly diagnosed MCL treated according to the recently published observational trial protocol (alternation of R-CHOP and R-cytarabine, 3 + 3 cycles, GovTrial number NCT03054883) at the centers that implemented RM. Minimal residual disease was evaluated by a EuroMRD standardized real-time PCR approach after 3 and 6 cycles of the induction therapy. Prognostic significance of MRD was analyzed in a subcohort of patients treated at the centers that implemented RM as a standard approach. Bone marrow proved to be a significantly more sensitive source for MRD detection than peripheral blood. In either compartment MRD (positive versus negative) after 3 or 6 cycles of the induction therapy did not correlate with PFS. The observed loss of prognostic significance of MRD after the R-CHOP-based induction appears to be a consequence of RM immune control over the residual lymphoma.
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http://dx.doi.org/10.1002/hon.2550DOI Listing
December 2018

Nonfunctioning parathyroid carcinoma associated with parathyromatosis. A case report.

Cesk Patol Spring 2018;54(1):37-42

We report on the case of a 39-year old man who underwent a thyroidectomy and a parathyroidectomy with misdiagnosed medullary carcinoma of the thyroid in 2013. During the operation the thyroid gland and parathyroid glands were artificially damaged due to the complicated surgical access to the glands because of the obesity of the patient as well as the deep placement of the enlarged parathyroid glands. Three years later, the neck ultrasound showed bilateral nodules on the neck, suspected to be metastases of the medullary carcinoma. Microscopically, the nodules were found to be focuses of parathyromatosis, and there was also an infiltrating carcinoma. This lesion was reclassified after clinico-pathological correlation and immunohistochemical examination as nonfunctioning parathyroid carcinoma. This article discusses morphological and immunohistochemical features of parathyromatosis and parathyroid carcinoma and its separation from lesions with which it may be misdiagnosed.
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April 2019

[Molecular mechanisms of primary and secondary resistance, molecular-genetic features and characteristics of KIT/PDGFRA non-mutated GISTs].

Cesk Patol Winter 2017;53(4):167-173

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Most of them arise due to activating mutations in KIT (75 - 85 %) or PDGFRA (less than 10 %) genes. Identification of the activating mutations in KIT and PDGFRA genes, which code for receptor tyrosine kinases (RTKs), has improved the outcome of targeted therapy of metastatic, unresectable or recurrent GISTs. Primary and/or secondary resistance represents a significant problem in the targeted therapy by Imatinib mesylate (IM) in patients with GIST. An important mechanism of the secondary resistance is the evolvement of secondary mutations. Except for primary and secondary resistance, there is another problem of disease progression - a failure of tumor cells eradication even in the long term therapy of tyrosine kinase inhibitors. GISTs without mutations in KIT/PDGFRA genes constitute 10 - 15% GISTs in adults, and a majority (85 %) of pediatric GISTs. KIT/PDGFRA wild-type GISTs represent a heterogeneous group of tumors with several molecular-genetics and/or morphologic differences. KIT/PDGFRA wild-type GISTs are different in their molecular features, for example in mutations in the BRAF, KRAS, NF1 genes or defects of succinate dehydrogenase (SDH) subunits. KIT/PDGFRA wild-type GISTs are generally less sensitive to targeted therapy by tyrosine kinase inhibitors in comparison with KIT/PDGFRA mutated GISTs. Inhibitors of BRAF, PI3K (mTOR) or inhibitors of IGF1R and VEGFR receptors provide alternative therapeutic strategies.
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April 2019

Alternating R-CHOP and R-cytarabine is a safe and effective regimen for transplant-ineligible patients with a newly diagnosed mantle cell lymphoma.

Hematol Oncol 2018 Feb 30;36(1):110-115. Epub 2017 Oct 30.

First Medical Department, Charles University General Hospital in Prague, Prague, Czech Republic.

Implementation of cytarabine into induction therapy became standard of care for younger patients with mantle cell lymphoma (MCL). On the basis of its beneficial impact, many centers incorporated cytarabine at lower doses also into first-line treatments of elderly patients. We conducted a multicenter observational study that prospectively analyzed safety and efficacy of alternating 3 + 3 cycles of R-CHOP and R-cytarabine for newly diagnosed transplant-ineligible MCL patients. A total of 73 patients were enrolled with median age 70 years. Most patients had intermediate (39.7%) and high-risk (50.7%) disease according to MCL international prognostic index. Rituximab maintenance was initiated in 58 patients. Overall response rate reached 89% by positron emission tomography-computed tomography, including 75.3% complete remissions. Two patients (2.7%) did not complete the induction therapy because of toxicity. Three patients (4.1%) were considered nonresponders, which led to therapy change before completion of induction. Estimated progression-free survival and overall survival were 51.3% and 68.6% at 4 years, respectively. Mantle cell lymphoma international prognostic index, bulky disease (≥ 5 cm), and achievement of positron emission tomography-negativity independently correlated with progression-free survival. Grade 3 to 4 hematologic and nonhematologic toxicity was documented in 48% and 20.5% patients, respectively. Alternation of R-CHOP and R-cytarabine represents feasible and very effective regimen for elderly/comorbid MCL patients. This study was registered at GovTrial (clinicaltrials.gov) NCT03054883.
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http://dx.doi.org/10.1002/hon.2483DOI Listing
February 2018

Expression of oxysterol pathway genes in oestrogen-positive breast carcinomas.

Clin Endocrinol (Oxf) 2017 Jun 24;86(6):852-861. Epub 2017 Apr 24.

Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic.

Objective: This study investigated whether gene expression levels of key modulators of the oxysterol signalling pathway modify the prognosis of patients with oestrogen receptor-positive (ER+) breast carcinomas via interaction with endocrine therapy.

Context: The prognosis of patients with ER+ breast carcinoma depends on several factors. Previous studies have suggested that some oxygenated forms of cholesterol (oxysterols) bind to oestrogen receptor and anti-oestrogen binding site which may deregulate cholesterol homoeostasis and influence effect of therapy.

Design: The expression levels of 70 oxysterol pathway genes were evaluated in a test set of breast carcinomas differing in ER expression. The genes differentially expressed in ER+ tumours were assessed in a comprehensive set of ER+ tumours to evaluate their clinical significance.

Patients: A total of 193 primary patients with breast carcinoma were included.

Measurements: The transcript levels were determined by quantitative real-time polymerase chain reaction.

Results: The expression levels of 23 genes were found to be specifically dysregulated in ER+ tumours compared to ER- tumours of the test set. The expression levels of ABCG2, CYP7B1, CYP24A1, CYP39A1 and CH25H genes were found to be strongly associated with disease stage; however, none of the gene expression levels were associated with disease-free survival in patients treated with endocrine therapy.

Conclusions: The expression of a number of oxysterol pathway genes is significantly modulated by ER expression and associated with the clinical stage of patients. However, the expression of oxysterol pathway genes was not found to modify the prognosis of ER+ patients with breast carcinoma treated with endocrine therapy.
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http://dx.doi.org/10.1111/cen.13337DOI Listing
June 2017

A t(4;19) pediatric undifferentiated sarcoma with a novel variant of the CIC-DUX4 fusion transcript.

Pathol Res Pract 2017 Mar 16;213(3):281-285. Epub 2016 Dec 16.

Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czechia.

We report cytogenetic and molecular genetic analysis of a pediatric tumor positive for the CIC-DUX4 fusion. The tumor belongs to a rare, diagnostically challenging subgroup of undifferentiated small round cell sarcomas. A balanced t(4;19)(q35;q13.1-2) was identified by G-banding, as a sole cytogenetic finding. The translocation was also identified by the M-FISH technique. After RT-PCR, the tumor sample was positive for the CIC-DUX4 fusion. The PCR product contains a novel, so far unreported variant of the CIC-DUX4 fusion transcript, with a fusion of the exon 20 from the CIC gene and the exon 1 from the DUX4 gene.
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http://dx.doi.org/10.1016/j.prp.2016.12.005DOI Listing
March 2017

Odontogenic keratocysts in the Basal Cell Nevus (Gorlin-Goltz) Syndrome associated with paresthesia of the lower jaw: Case report, retrospective analysis of a representative Czech cohort and recommendations for the early diagnosis.

Neuro Endocrinol Lett 2016 Sep;37(4):269-276

Department of Stomatology, Charles University 2nd Faculty of Medicine and University Hospital in Motol, Prague, Czech Republic.

Objectives: Identification of early presenting signs of the Basal Cell Nevus (BCNS; synonyme Gorlin-Goltz) syndrome, which is associated with a principal triad of multiple basal cell nevi, jaw odontogenic keratocysts, and skeletal anomalies, in stomatological and neurological practices. Proposal of multidisciplinary diagnostic algorithm comprising other medical specialists, including pathology, imaging, laboratory and molecular analyses based on the study outcomes.

Design: Case report of a male patient reporting paresthesia of their lower jaw, with right facial asymmetry (maxilla and mandible) and radiological detection of large osteolytic lesions in both jaws, including a retrospective analysis of a representative Czech cohort with BCNS from within the last decade.

Setting: Clinical, imaging and laboratory analyses were carried out at a national tertiary centre.

Results: A multidisciplinary clinical approach followed by surgical management lead to the identification of odontogenic cysts, which were substantiated by histological examination. DNA sequencing of the PTCH1 gene detected a c.2929dupT resulting in p. Tyr977Leufs*16 pathogenic variant. This finding confirmed the clinical and laboraoty diagnosis of BCNS. Parental DNA analysis showed that this causal genetic defect arose de novo. Surgical management and orthodontic therapy were successful.

Conclusions: Analysis of the reported case and retrospective data analysis provided evidence that paresthesia of the lower jaw should be considered as one of the early presenting signs of this rare disorder in stomatological and neurological practice. Obtained results allowed us to formulate recommendations for diagnostic practice in stomatology and neurology.
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September 2016

Genetic and functional analyses do not explain the association of high PRC1 expression with poor survival of breast carcinoma patients.

Biomed Pharmacother 2016 Oct 6;83:857-864. Epub 2016 Aug 6.

Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic; Biomedical Centre, Faculty of Medicine in Plzen, Charles University in Prague, Plzen, Czech Republic. Electronic address:

Microtubules are vitally important for eukaryotic cell division. Therefore, we evaluated the relevance of mitotic kinesin KIF14, protein-regulating cytokinesis 1 (PRC1), and citron kinase (CIT) for the prognosis of breast carcinoma patients. Transcript levels were assessed by quantitative real-time PCR in tissues from two independent groups of breast carcinoma patients and compared with clinical data. Tissue PRC1 protein levels were estimated using immunoblotting, and the PRC1 tagged haplotype was analyzed in genomic DNA. A functional study was performed in MDA-MB-231 cells in vitro. KIF14, PRC1, and CIT transcripts were overexpressed in tumors compared with control tissues. Tumors without expression of hormonal receptors or high-grade tumors expressed significantly higher KIF14 and PRC1 levels than hormonally-positive or low-grade tumors. Patients with high intra-tumoral PRC1 levels had significantly worse disease-free survival than patients with low levels. PRC1 rs10520699 and rs11852999 polymorphisms were associated with PRC1 transcript levels, but not with patientś survival. Paclitaxel-induced PRC1 expression, but PRC1 knockdown did not modify the paclitaxel cytotoxicity in vitro. PRC1 overexpression predicts poor disease-free survival of patients with breast carcinomas. Genetic variability of PRC1 and the protein interaction with paclitaxel cytotoxicity do not explain this association.
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http://dx.doi.org/10.1016/j.biopha.2016.07.047DOI Listing
October 2016

High-grade urothelial bladder cancer in children: A case report and critical analysis of the literature.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2016 Dec 3;160(4):578-582. Epub 2016 Oct 3.

Department of Urology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic.

Background: Bladder cancer is relatively common in adults. In children, it is extremely rare and in the majority of cases, low grade, low stage urothelial cancers are found.

Case Report: We describe the diagnostic, therapeutic, and follow-up management of bladder cancer in a 3-year-old boy examined for painless hematuria. Transurethral resection of the tumor was performed and T1 high grade urothelial cancer with osseous metaplasia was found in definitive specimens. During the 2-year follow-up, there has been no recurrence. Typical characteristics of the most prevalent bladder tumors are presented.

Conclusion: Despite its low incidence and low prevalence bladder cancer in children is a very serious condition which must not be missed in the differential diagnosis of hematuria or urinary tract infection. It is vital to differentiate urothelial cancer from hamartoma and nephrogenic adenoma and, particularly in osseous metaplasia, from sarcomatoid carcinoma. Especially in high-grade cancers, precise TUR of the tumor with a careful follow-up is essential to detect cancer recurrence and reduce progression.
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http://dx.doi.org/10.5507/bp.2016.045DOI Listing
December 2016

[Sinus histiocytosis with massive lymphadenopathy: FDG-PET/CT documented partial remission after treatment with 2-chlorodeoxyadenosine].

Vnitr Lek Summer 2016;62(6):491-9

Unlabelled: Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) is a very rare disease belonging to a group of histiocytoses (more precisely non-Langerhans cell histiocytoses). Rosai-Dorfman disease is characterised by the presence of atypical histiocytic cells in the sinuses of lymph nodes or in the extranodal lymphoid tissue, absorbing lymphocytes and plasma cells. The structure and function of the absorbed cells is not impaired and they can leave histiocytes as viable cells. This effect is called emperipolesis, whereas ingestion of cells with their destruction is called phagocytosis. In our text we describe a patient with this disease located, characteristically, in supraclavicular lymph nodes, but also in mediastinal lymph nodes. Along with lymphadenopathy skin alterations appeared which were both clinically and histologically described as eczema dermatitis. At the same time as lymphadenopathy also strong headaches started which the patient had never suffered before. Within the first-line treatment prednisone was administered, but no effect was achieved. 2-chlorodeoxyadenosine in 5 mg/m2 s. c. dose was used in the second-line treatment, for 5 successive days in monthly intervals. There were four cycles of this treatment administered overall. Therapy was tolerated without any manifestations of toxicity. Already after the 1st cycle skin alterations as well as headaches entirely disappeared. To assess the effect of treatment the PET/CT examination with 18F-fluorodeoxyglucose (FDG-PET/CT) was made. After 4 cycles of treatment the mediastinal lymph nodes diminished to a physiological size and the accumulation of fluorodeoxyglucose in them was assessed as physiological. Lymphadenopathy in the neck area also significantly diminished by 50-75 % and the accumulation of fluorodeoxyglucose was reduced as well, though it did not reach the norm. Therefore we evaluate the effect of treatment as a partial remission with complete disappearance of skin alterations and headaches. The cause of the eczema and headaches has not been clarified, however considering the same time of their arising and then disappearance after the application of 2-chlorodeoxyadenosine the causal connection with Rosai-Dorfman disease is likely.

Key Words: Castlemans disease - lenalidomide - Rosai-Dorfman disease - rituximab - sinus lymphadenopathy with massive lymphadenopathy - thalidomide - 2-chlorodeoxyadenosine.
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June 2017

Transcript expression and genetic variability analysis of caspases in breast carcinomas suggests CASP9 as the most interesting target.

Clin Chem Lab Med 2017 Jan;55(1):111-122

Background: Apoptosis plays a critical role in cancer cell survival and tumor development. We provide a hypothesis-generating screen for further research by exploring the expression profile and genetic variability of caspases (2, 3, 7, 8, 9, and 10) in breast carcinoma patients. This study addressed isoform-specific caspase transcript expression and genetic variability in regulatory sequences of caspases 2 and 9.

Methods: Gene expression profiling was performed by quantitative real-time PCR in tumor and paired non-malignant tissues of two independent groups of patients. Genetic variability was determined by high resolution melting, allelic discrimination, and sequencing analysis in tumor and peripheral blood lymphocyte DNA of the patients.

Results: CASP3 A+B and S isoforms were over-expressed in tumors of both patient groups. The CASP9 transcript was down-regulated in tumors of both groups of patients and significantly associated with expression of hormonal receptors and with the presence of rs4645978-rs2020903-rs4646034 haplotype in the CASP9 gene. Patients with a low intratumoral CASP9A/B isoform expression ratio (predicted to shift equilibrium towards anti-apoptotic isoform) subsequently treated with adjuvant chemotherapy had a significantly shorter disease-free survival than those with the high ratio (p=0.04). Inheritance of CC genotype of rs2020903 in CASP9 was associated with progesterone receptor expression in tumors (p=0.003).

Conclusions: Genetic variability in CASP9 and expression of its splicing variants present targets for further study.
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http://dx.doi.org/10.1515/cclm-2016-0271DOI Listing
January 2017

Prognostic Value of Ki-67 Index, Cytology, and Growth Pattern in Mantle-Cell Lymphoma: Results From Randomized Trials of the European Mantle Cell Lymphoma Network.

J Clin Oncol 2016 Apr 29;34(12):1386-94. Epub 2016 Feb 29.

Eva Hoster, Roswitha Forstpointner, Christian Schmidt, Wolfgang Hiddemann, Michael Unterhalt, and Martin H. Dreyling, University Hospital Munich; Eva Hoster, University of Munich, Munich; Andreas Rosenwald, University of Würzburg, Würzburg; Heinz-Wolfram Bernd, University Hospital Schleswig-Holstein, Lübeck; Sylvia Hartmann, University Hospital of Frankfurt, Frankfurt am Main; Christoph Loddenkemper, University Hospital Berlin Charité; Christoph Loddenkemper, Pathologie PathoTres, Berlin; Thomas F.E. Barth, University Medical Center Ulm; Stephan Stilgenbauer, University of Ulm, Ulm; Michael Hallek, Universität zu Köln, Köln; Ursula Vehling-Kaiser, Tagesklinik Hämatologie Onkologie, Landshut; Lothar Kanz, University of Tübingen, Tübingen; Michael Pfreundschuh, Universitätsklinik des Saarlandes, Homburg; Wolfram Klapper, University of Kiel, Kiel, Germany; Françoise Berger, LYSA Group; Nicole Brousse, Hopital Necker; Catherine Thieblemont, Hôpital Saint Louis; Olivier Hermine, University Paris Descartes; Olivier Hermine, Université Sorbonne Paris Cité, Paris; Bertrand Coiffier, Centre Hospitalier Lyon-Sud, Pierre-Bénite; Réda Bouabdallah, Service d'Hématologie, Marseille; Vincent Ribrag, Institut Gustave Roussy, Villejuif, France; Stefano Pileri, University of Bologna, Bologna, Italy; Grzegorz Rymkiewicz, The Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland; Roman Kodet, Charles University, Prague, Czech Republic; and Johanna C. Kluin-Nelemans, University of Groningen, Groningen, The Netherlands.

Purpose: Mantle-cell lymphoma (MCL) is a rather aggressive B-cell malignancy whose considerable variability of individual outcome is associated with clinical characteristics (Mantle Cell Lymphoma International Prognostic Index [MIPI]). The Ki-67 index is a strong independent prognostic factor; however, the biologic MIPI (MIPI-b) distinguishes only two groups, which does not appropriately depict the clinical heterogeneity. By using the cohort from the European MCL Younger and MCL Elderly trials, we aimed to evaluate the additional prognostic impact of cytology and growth pattern and to improve risk stratification with the Ki-67 index and MIPI.

Patients And Methods: Diagnostic tumor biopsies were reviewed by the European Mantle Cell Lymphoma Pathology Panel to determine Ki-67 index by using published guidelines, cytology, and growth pattern. We evaluated prognostic effects for overall survival (OS) by Cox regression. For the cohort used for MIPI-b development (German Low-Grade Lymphoma Study Group [GLSG] 1996 and GLSG2000), we checked whether the equally weighted combination of Ki-67 index (dichotomized at the validated 30% cutoff) and MIPI risk groups was adequate and compared the prognostic power of this modified combination to MIPI and MIPI-b for the MCL Younger/MCL Elderly cohort.

Results: The Ki-67 index was assessed in 508 of 832 patients (median age, 62 years). Blastoid cytology was associated with inferior OS independently of MIPI but not independently of the Ki-67 index. Growth pattern was not independently prognostic. The modified combination of the Ki-67 index and MIPI separated four groups with 5-year OS: 85%, 72%, 43%, and 17% (P < .001) and was more discriminative than MIPI and MIPI-b.

Conclusion: Using the Ki-67 index is superior to using cytology and growth pattern as prognostic factors in MCL. The modified combination of the Ki-67 index and MIPI showed a refined risk stratification, reflecting their strong complementary prognostic effects while integrating the most relevant prognostic factors available in clinical routine.
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http://dx.doi.org/10.1200/JCO.2015.63.8387DOI Listing
April 2016

Fanconi anemia with biallelic FANCD1/BRCA2 mutations - Case report of a family with three affected children.

Eur J Med Genet 2016 Mar 2;59(3):152-7. Epub 2015 Dec 2.

Department of Pediatric Hematology and Oncology, Charles University in Prague, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.

Fanconi anemia, complementation group D1 with bi-allelic FANCD1 (BRCA2) mutations, is a very rare genetic disorder characterized by early onset of childhood malignancies, including acute leukemia, brain cancer and nephroblastoma. Here, we present a case report of a family with 3 affected children in terms of treatment outcome, toxicity and characterization of the malignancies using comprehensive cytogenetic analysis. The first child was diagnosed with T-cell acute lymphoblastic leukemia when he was 11 months old. During chemotherapy, he suffered from repeated pancytopenia, sepsis and severe vincristine polyneuropathy, and 18 months after primary diagnosis, he succumbed to secondary acute monocytic leukemia. The second child was diagnosed with stage 2 triphasic nephroblastoma (Wilms tumor), when he was 3 years and 11 months old. During chemotherapy, he suffered from vincristine polyneuropathy. Currently, he is in complete remission, 29 months following the initial diagnosis. The third child was diagnosed with medulloblastoma with classical histology, when she was 4 years and 5 months old. After the first cycle of chemotherapy, she suffered from prolonged pancytopenia, sepsis and severe skin and mucosal toxicity. Six weeks after primary diagnosis, a first relapse in the posterior fossa was diagnosed, and at 7 and half months after primary diagnosis, a second relapse was diagnosed that led to the patient's death. Our case report underscores tumor heterogeneity, treatment toxicity and poor outcome in Fanconi anemia patients of complementation group D1.
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http://dx.doi.org/10.1016/j.ejmg.2015.11.013DOI Listing
March 2016

[Periosteal osteosarcoma - personal experience with five cases].

Cesk Patol 2015 ;51(4):193-8

The authors present five cases of periosteal osteosarcoma located in the femur (4) and tibia (1) in children and young adults (1 female and 4 males) with an age range of 9 - 23 years (mean age 15 years). Radiographs in all cases showed a broad-based soft tissue mass attached to the cortex with periosteal reaction and in two of them cortical disruption with extensive medullary involvement. Follow-ups were available in four cases (range 11 - 73 months) and revealed pelvic metastasis after 15 months with ultimately rapid dissemination and death in a 9-year-old girl and metastasis to the humerus after 13 months in a 15-year-old boy. The former tumor widely extended into the medullary cavity and an amputation was carried out, the latter had a pure juxtacortical position and an en block resection was performed; both of them were treated with chemotherapy. All the lesions displayed distinctive structural patterns combining a large island of tumorous cartilage and hypocellular, bland-looking myxoid mesenchymal stroma with abrupt transition between both components. Contrary to conventional osteosarcoma, the delicate flocculent osteoid deposits were produced by innocuous stromal cells lacking apparent atypia. They were strictly situated outside the prevailing chondroid areas and disclosed sometimes only after a meticulous search. Immunohistochemical detection of SATB2, S100protein and D2-40 assisted effectively not only in recognition of the real stromal histogenetic derivation, but also in distinction of true differentiation of a heavily mineralized extracellular matrix. Molecular analysis revealed no IDH1/2 mutation in four examined cases. Regardless of unique low-grade morphology in rare periosteal osteosarcoma, an aggressive therapeutical approach similar to conventional osteosarcoma is justified, particularly in the case of a medullary extension.
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May 2016

Targeting of BCL2 Family Proteins with ABT-199 and Homoharringtonine Reveals BCL2- and MCL1-Dependent Subgroups of Diffuse Large B-Cell Lymphoma.

Clin Cancer Res 2016 Mar 14;22(5):1138-49. Epub 2015 Oct 14.

Institute of Pathological Physiology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic. First Department of Medicine - Department of Hematology, General University Hospital and Charles University in Prague, Prague, Czech Republic.

Purpose: To investigate the roles of BCL2, MCL1, and BCL-XL in the survival of diffuse large B-cell lymphoma (DLBCL).

Experimental Designs: Immunohistochemical analysis of 105 primary DLBCL samples, and Western blot analysis of 18 DLBCL cell lines for the expression of BCL2, MCL1, and BCL-XL. Pharmacologic targeting of BCL2, MCL1, and BCL-XL with ABT-199, homoharringtonine (HHT), and ABT-737. Analysis of DLBCL clones with manipulated expressions of BCL2, MCL1, and BCL-XL. Immunoprecipitation of MCL1 complexes in selected DLBCL cell lines. Experimental therapy aimed at inhibition of BCL2 and MCL1 using ABT-199 and HHT, single agent, or in combination, in vitro and in vivo on primary cell-based murine xenograft models of DLBCL.

Results: By the pharmacologic targeting of BCL2, MCL1, and BCL-XL, we demonstrated that DLBCL can be divided into BCL2-dependent and MCL1-dependent subgroups with a less pronounced role left for BCL-XL. Derived DLBCL clones with manipulated expressions of BCL2, MCL1, and BCL-XL, as well as the immunoprecipitation experiments, which analyzed MCL1 protein complexes, confirmed these findings at the molecular level. We demonstrated that concurrent inhibition of BCL2 and MCL1 with ABT-199 and HHT induced significant synthetic lethality in most BCL2-expressing DLBCL cell lines. The marked cytotoxic synergy between ABT-199 and HHT was also confirmed in vivo using primary cell-based murine xenograft models of DLBCL.

Conclusions: As homoharringtonine is a clinically approved antileukemia drug, and ABT-199 is in advanced phases of diverse clinical trials, our data might have direct implications for novel concepts of early clinical trials in patients with aggressive DLBCL.
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http://dx.doi.org/10.1158/1078-0432.CCR-15-1191DOI Listing
March 2016

Lung cancer, pulmonary emphysema and pleural effusion: An autopsy study.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2015 Dec 19;159(4):642-7. Epub 2015 May 19.

Department of Pneumology, 2nd Faculty of Medicine, Charles University in Prague and Faculty Hospital Motol, Prague, Czech Republic.

Objectives: To determine the exact incidence of lung cancer, pulmonary emphysema and pleural effusion we decided to carry out an autopsy study.

Methods: In this autopsy study carried out over two years, we compared the results of autopsy findings with the clinical data in accompanying records of the deceased.

Results: Among the 708 deceased subjects, there were 398 males and 310 females with a median age of 71 years. At autopsy, 55 cases of lung carcinoma (BCA) were found, of which 24 have not been identified during life (44%). Among the deceased with BCA, emphysema was also observed at autopsy in 40% of the cases. Pulmonary emphysema was described macroscopically in 28% of the full set of 708 deceased, whereas the accompanying records of the deceased described this condition in only 12% of the cases. Microscopic changes compatible with emphysema were identified in 54% of the examined lungs. Pleural effusions were described in the accompanying records of 13% of the deceased, while the autopsies showed this condition in 33% of the deceased. BCA was accompanied by effusion in 25% of the cases.

Conclusions: The obtained results show that the studied conditions are present in more cases than are reported by clinicians. The study confirms the commonly accepted association between lung cancer and emphysema.
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http://dx.doi.org/10.5507/bp.2015.024DOI Listing
December 2015

[Not Available].

Cesk Patol 2014 Jan;50(1):33, 38-9

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January 2014

The role of cytochromes p450 and aldo-keto reductases in prognosis of breast carcinoma patients.

Medicine (Baltimore) 2014 Dec;93(28):e255

From the Toxicogenomics Unit (VH, VB, RV, ME, DV, PS), National Institute of Public Health; 3rd Faculty of Medicine (VH, VB, ME), Charles University, Prague; Department of Oncology (DV), Palacky University Medical School and Teaching Hospital, Olomouc; Institute for the Care for Mother and Child (VP); Biolab Praha, Ltd (MT); Department of Pathology and Molecular Medicine (RK, MM); Department of Oncology (KK), University Hospital Motol, Prague; Department of Surgery (JG), Hospital Atlas; Tomas Bata University (JG); and Department of Pathology (PV), VELAB Ltd, Zlin, Czech Republic.

Metabolism of anticancer drugs affects their antitumor effects. This study has investigated the associations of gene expression of enzymes metabolizing anticancer drugs with therapy response and survival of breast carcinoma patients. Gene expression of 13 aldo-keto reductases (AKRs), carbonyl reductase 1, and 10 cytochromes P450 (CYPs) was assessed using quantitative real-time polymerase chain reaction in tumors and paired adjacent nonneoplastic tissues from 68 posttreatment breast carcinoma patients. Eleven candidate genes were then evaluated in an independent series of 50 pretreatment patients. Protein expression of the most significant genes was confirmed by immunoblotting. AKR1A1 was significantly overexpressed and AKR1C1-4, KCNAB1, CYP2C19, CYP3A4, and CYP3A5 downregulated in tumors compared with control nonneoplastic tissues after correction for multiple testing. Significant association of CYP2B6 transcript levels in tumors with expression of hormonal receptors was found in the posttreatment set and replicated in the pretreatment set of patients. Significantly higher intratumoral levels of AKR1C1, AKR1C2, or CYP2W1 were found in responders to neoadjuvant chemotherapy compared with nonresponders. Patients with high AKR7A3 or CYP2B6 levels in the pretreatment set had significantly longer disease-free survival than patients with low levels. Protein products of AKR1C1, AKR1C2, AKR7A3, CYP3A4, and carbonyl reductase (CBR1) were found in tumors and those of AKR1C1, AKR7A3, and CBR1 correlated with their transcript levels. Small interfering RNA-directed knockdown of AKR1C2 or vector-mediated upregulation of CYP3A4 in MDA-MB-231 model cell line had no effect on cell proliferation after paclitaxel treatment in vitro. Prognostic and predictive roles of drug-metabolizing enzymes strikingly differ between posttreatment and pretreatment breast carcinoma patients. Mechanisms of action of AKR1C2, AKR7A3, CYP2B6, CYP3A4, and CBR1 should continue to be further followed in breast carcinoma patients and models.
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http://dx.doi.org/10.1097/MD.0000000000000255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603110PMC
December 2014

The use of formalin-fixed, paraffin-embedded lymph node samples for the detection of minimal residual disease in mantle cell lymphoma.

Br J Haematol 2015 Apr 14;169(1):145-8. Epub 2014 Oct 14.

Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, University Hospital Motol, Charles University in Prague, Prague, Czech Republic.

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http://dx.doi.org/10.1111/bjh.13182DOI Listing
April 2015

[Soft tissue tumors - the view of the molecular biologist].

Cesk Patol 2014 Jul;50(3):132-40

Soft tissue tumors (SSTs) constitute a broad spectrum of neoplasms with diverse biological properties. Rare or unusual types are often difficult to classify. Recent studies show, that a significant subset of SSTs including many types of sarcomas are associated with specific genetic changes such as chromosomal translocations producing chimeric genes, which play a role in the pathogenesis of SSTs. Because SSTs represent a diagnostically challenging group of tumors, molecular-genetic techniques (FISH or PCR) are useful as supplementary and/or confirmatory diagnostic tools. In the present paper we demonstrate the usefulness of a combined diagnostic approach using the tools of classical histopathology and immunohistochemistry together with the molecular diagnostic approach in selected nosologic entites.
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July 2014

[A complex diagnostic approach in lymphomas: practical aspect in short case reports].

Cesk Patol 2014 Jul;50(3):118-26

Complex laboratory investigation is necessary for the diagnosis and relevant classification of lymphomas. The classical histopathological morphology and cytology investigation is essential, but further investigations such as immunohistochemistry and fluorescence in situ hybridization are necessary. It is also important to employ flow cytometry as a method of investigation running synchronously or preceding the histopathological approach. Last but not least, the investigation of nucleic acids in lymphoma by molecular approaches is necessary and has become an everyday practice. Communication between pathologists and clinical colleagues (oncologists, hematologists, internal medicine specialists and radiologists) is very important. We demonstrate the necessity of a complex diagnostic approach to lymphomas and an appropriate interpretation of all laboratory investigations giving examples of eight patients with various types of lymphomas. In some cases, it is impossible to properly diagnose a lymphoma without molecular investigation. Occasionally, the results of the molecular investigation may be misleading and/or may be inaccurately interpreted, leading to an incorrect conclusion. For that reason, it is very important to incorporate all specialized laboratories and their teams under one roof (preferably that of pathology departments), enabling tight and daily cooperation between the specialists. This is the way to reach a precise diagnosis in a majority of cases, as well as how to comply with clinical expectations of properly classified lymphomas for a targeted therapy of patients.
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July 2014
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