Publications by authors named "Ireneusz Dziuba"

9 Publications

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Entosis: From Cell Biology to Clinical Cancer Pathology.

Cancers (Basel) 2020 Sep 1;12(9). Epub 2020 Sep 1.

Department of Histology and Embryology, Medical University of Warsaw, 02-004 Warszawa, Poland.

Entosis is a phenomenon, in which one cell enters a second one. New clinico-histopathological studies of entosis prompted us to summarize its significance in cancer. It appears that entosis might be a novel, independent prognostic predictor factor in cancer histopathology. We briefly discuss the biological basis of entosis, followed by a summary of published clinico-histopathological studies on entosis significance in cancer prognosis. The correlation of entosis with cancer prognosis in head and neck squamous cell carcinoma, anal carcinoma, lung adenocarcinoma, pancreatic ductal carcinoma and breast ductal carcinoma, is shown. Numerous entotic figures are associated with a more malignant cancer phenotype and poor prognosis in many cancers. We also showed that some anticancer drugs could induce entosis in cell culture, even as an escape mechanism. Thus, entosis is likely beneficial for survival of malignant cells, i.e., an entotic cell can hide from unfavourable factors in another cell and subsequently leave the host cell remaining intact, leading to failure in therapy or cancer recurrence. Finally, we highlight the potential relationship of cell adhesion with entosis in vitro, based on the model of the BxPc3 cells cultured in full adhesive conditions, comparing them to a commonly used MCF7 semiadhesive model of entosis.
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http://dx.doi.org/10.3390/cancers12092481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563411PMC
September 2020

Colorectal Adenocarcinomas Harboring ALK Fusion Genes: A Clinicopathologic and Molecular Genetic Study of 12 Cases and Review of the Literature.

Am J Surg Pathol 2020 09;44(9):1224-1234

Surgical Pathology, Holycross Cancer Center.

This study determined the frequency and the clinicopathologic and genetic features of colorectal carcinomas driven by oncogenic fusions of the anaplastic lymphoma kinase gene (ALK). Of the 8150 screened tumors, 12 (0.15%) were immunohistochemically ALK-positive with D5F3 antibody. These cancers harbored CAD-ALK (n=1), DIAPH2-ALK (n=2), EML4-ALK (n=2), LOC101929227-ALK (n=1), SLMAP-ALK (n=1), SPTBN1-ALK (n=4), and STRN-ALK (n=1) fusions, as detected by an RNA-based next-generation sequencing assay. ALK fusion carcinomas were diagnosed mostly in older patients with a 9:3 female predominance (median age: 72 y). All tumors, except a rectal one, occurred in the right colon. Most tumors were stage T3 (n=7) or T4 (n=3). Local lymph node and distant metastases were seen at presentation in 9 and 2 patients. These tumors showed moderate (n=6) or poor (n=3) glandular differentiation, solid medullary growth pattern (n=2), and pure mucinous morphology (n=1). DNA mismatch repair-deficient phenotype was identified in 10 cases. Tumor-infiltrating lymphocytes were prominent in 9 carcinomas. In 4 carcinomas, tumor cells showed strong, focal (n=3), or diffuse programmed death-ligand 1 immunoreactivity. CDX2 expression and loss of CK20 and MUC2 expression were frequent. CK7 was expressed in 5 tumors. Four patients died of disease within 3 years, and 7 were alive with follow-up ranging from 1 to 8 years. No mutations in BRAF, RAS, and in genes encoding components of PI3K-AKT/MTOR pathway were identified. However, 1 tumor had a loss-of-function PTEN mutation. Aberration of p53 signaling, TP53 mutations, and/or nuclear accumulation of p53 protein was seen in 9 cases. ALK fusion colorectal carcinomas are a distinct and rare subtype of colorectal cancers displaying some features of mismatch repair-deficient tumors.
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http://dx.doi.org/10.1097/PAS.0000000000001512DOI Listing
September 2020

Chronic Subdural Hematoma (CSH) is Still an Important Clinical Problem. Analysis of 700 Consecutive Patients.

Transl Neurosci 2019 6;10:260-263. Epub 2019 Nov 6.

Department of Neurosurgery, Faculty of Health Sciences and Physical Education, Kazimierz Pulaski University of Technology and Humanities, Radom, Poland.

Background: Chronic subdural hematoma (CSH) is still an important neurosurgical problem and the number of patients increases despite the progress in early diagnosis of cerebral lesions.

Methodology: We analyzed a group of 700 consecutive patients treated in neurosurgical departments for CSH. Clinical state on admission was evaluated according to the Markwalder scale, all patients had CT studies and were operated using craniotomy or burr holes with closed system drainage techniques.

Results: More than 50% had extensive intracranial bleeding, almost half of the patients were treated with oral anticoagulants. The patients with extensive fresh bleeding were in significantly worse states on admission and were treated by craniotomy and external capsulectomy (42%). All the others had burr holes and closed system drainage of the subdural space. Results of treatment were acceptable, 2% died, and 1.5% remained vegetative, due to massive hemorrhage and severe neurological deficits on admission.

Conclusions: Despite a progress in diagnosis, CSH still remains an often cause of severe intracranial complications. The rising number of occurrences of this lesion is strictly connected with a wide use of oral anticoagulants. Surgical removal of CSH still remains the best type of treatment for such lesions.
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http://dx.doi.org/10.1515/tnsci-2019-0042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843484PMC
November 2019

Colonic Adenocarcinomas Harboring NTRK Fusion Genes: A Clinicopathologic and Molecular Genetic Study of 16 Cases and Review of the Literature.

Am J Surg Pathol 2020 02;44(2):162-173

Department of Pathomorphology, Jagiellonian University.

This study was undertaken to determine the frequency, and the clinicopathologic and genetic features, of colon cancers driven by neurotrophic receptor tyrosine kinase (NTRK) gene fusions. Of the 7008 tumors screened for NTRK expression using a pan-Trk antibody, 16 (0.23%) had Trk immunoreactivity. ArcherDx assay detected TPM3-NTRK1 (n=9), LMNA-NTRK1 (n=3), TPR-NTRK1 (n=2) and EML4-NTRK3 (n=1) fusion transcripts in 15 cases with sufficient RNA quality. Patients were predominantly women (median age: 63 y). The tumors involved the right (n=12) and left colon unequally and were either stage T3 (n=12) or T4. Local lymph node and distant metastases were seen at presentation in 6 and 1 patients, respectively. Lymphovascular invasion was present in all cases. Histologically, tumors showed moderate to poor (n=11) differentiation with a partly or entirely solid pattern (n=5) and mucinous component (n=10), including 1 case with sheets of signet ring cells. DNA mismatch repair-deficient phenotype was seen in 13 cases. Tumor-infiltrating CD4/CD8 lymphocytes were prominent in 9 cases. Programmed death-ligand 1 positive tumor-infiltrating immune cells and focal tumor cell positivity were seen in the majority of cases. CDX2 expression and loss of CK20 and MUC2 expression were frequent. CK7 was expressed in 5 cases. No mutations in BRAF, RAS, and PIK3CA were identified. However, other genes of the PI3K-AKT/MTOR pathway were mutated. In several cases, components of Wnt/β-catenin (APC, AMER1, CTNNB1), p53, and TGFβ (ACVR2A, TGFBR2) pathways were mutated. However, no SMAD4 mutations were found. Two tumors harbored FBXW7 tumor suppressor gene mutations. NTRK fusion tumors constitute a distinct but rare subgroup of colorectal carcinomas.
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http://dx.doi.org/10.1097/PAS.0000000000001377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170835PMC
February 2020

DNA variants in Helicobacter pylori infected patients with chronic gastritis, dysplasia and gastric cancer.

Adv Med Sci 2019 Mar 13;64(1):79-84. Epub 2018 Dec 13.

Department of Biochemistry and Biotechnology, Poznan University of Life Sciences, Poznan, Poland; Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland. Electronic address:

Purpose: The main scope of this study was to evaluate the importance of selected DNA variants for developing inflammation of gastric mucosa and carcinogenesis in gastrointestinal diseases in patients infected with Helicobacter pylori.

Patients And Methods: Patients subjected to analysis constituted a group of 131 consecutive cases, with control groups consisting of 100 healthy volunteers and 13 dyspeptic patients. Molecular analysis included the following genes: TP53 (c.743 G > A, c.746 G > A, c.749C > T), MSH2 (c.942 + 3A > T), MLH1 (c.2041 G > A), NOD2/CARD15 (c.3016_3017insC, c.802C > T), IL1A (c.-949C > T) and IL1B (c.315C > T). DNA variants were detected using PCR-RFLP, pyrosequencing and sequencing.

Results: Mutations of the analyzed genes were observed more frequently in patients with a higher degree of mucosal lesions (50.9%) than in patients with milder mucosal changes (27.6%). Single mutations and polymorphisms did not affect the course of the disease. Our analysis confirms the influence of the NOD2/CARD15 c.802C > T polymorphism on the development of mucosal changes. A correlation of the frequency of the CT genotype of the NOD2/CARD15 c.802C > T polymorphism with the NOD2/CARD15 c.3016_3017insC mutation was observed. The TT genotype frequency in the c.315C > T IL1B gene polymorphism was statistically significantly higher in patients with mucosa changes.

Conclusions: Accumulation of molecular abnormalities may increase the susceptibility to inflammatory response of the gastric mucosa in H. pylori-infected patients and play an important role in the development of chronic active gastritis, atrophy, intestinal metaplasia, dysplasia and the intestinal type of gastric cancer. The severity of gastric mucosal damage correlates with the presence of mutations in the gastric mucosa and the age of patients.
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http://dx.doi.org/10.1016/j.advms.2018.12.002DOI Listing
March 2019

Rhabdomyosarcoma in children - current pathologic and molecular classification.

Pol J Pathol 2018;69(1):20-32

The last 25 years have brought significant progress in the treatment of sarcomas in children, especially rhabdomyosarcoma (RMS). Nevertheless, treatment failure in some patients results from considerable biological heterogeneity noted in these tumours. RMS, the most common malignant soft tissue neoplasm in children, includes two main subtypes: embryonal (ERMS) and alveolar (ARMS). Due to greater aggressiveness and worse prognosis of ARMS in comparison to ERMS, discrimination between different rhabdomyosarcoma subtypes is of crucial clinical importance. This paper presents the current histological classification of RMS, up-to-date immunohistochemical and biological research regarding RMS, and its associated clinical and prognostic significance.
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http://dx.doi.org/10.5114/pjp.2018.75333DOI Listing
July 2018

Interleukin-1 gene polymorphisms in chronic gastritis patients infected with Helicobacter pylori as risk factors of gastric cancer development.

Arch Immunol Ther Exp (Warsz) 2013 Dec 31;61(6):503-12. Epub 2013 Aug 31.

Department of Internal Medicine, District Hospital, Drawsko Pomorskie, Poland.

Epidemiological investigations indicated association of the Helicobacter pylori infections with the occurrence of inflammatory conditions of the gastric mucosa and development of chronic gastritis and intestinal type of gastric cancer. IL1A and IL1B genes have been proposed as key factors in determining risk of gastritis and malignant transformation. The aim of this paper was to evaluate association of interleukin-1 gene polymorphisms with chronic gastritis, atrophy, intestinal metaplasia, dysplasia and intestinal type of gastric cancer in H. pylori-infected patients. Patients subjected to analysis represent group of 144 consecutive cases that suffered from dyspepsia with coexisting infection of H. pylori and chronic gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia or gastric cancer. Molecular studies involved analysis of -889C>T polymorphism of IL1A gene and +3954C>T polymorphism of IL1B gene. Statistical analysis of association of polymorphism -889C>T of gene IL1A with changes in gastric mucosa showed lack of significance, whereas +3954C>T polymorphism of IL1B gene showed significant association. Frequency of allele T of +3954C>T polymorphism of IL1B gene was higher in group of patients with chronic gastritis, atrophy, intestinal metaplasia, dysplasia or intestinal type of gastric cancer (32.1 %) as compared with population group (23 %), χ(2) = 4.61 and p = 0.03. This corresponds to odds ratio: 1.58, 95 % CI: 1.04-2.4. Our results indicate that +3954C>T polymorphism of IL1B gene increase susceptibility to inflammatory response of gastric mucosa H. pylori-infected patients and plays a significant role in the development of chronic gastritis, atrophy, intestinal metaplasia, dysplasia and the initiation of carcinogenesis.
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http://dx.doi.org/10.1007/s00005-013-0245-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898137PMC
December 2013

CHEK2 mutations and HNPCC-related colorectal cancer.

Int J Cancer 2010 Jun;126(12):3005-9

International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, il. Połabska 4, Szczecin, Poland.

Recently, the 1100delC variant of cell cycle checkpoint kinase 2 (CHEK2) has been reported to confer a colorectal cancer risk in hereditary non-polyposis-colorectal cancer (HNPCC) and HNPCC-related families in the Netherlands. To investigate whether CHEK2 mutations confer increased cancer risk in HNPCC and HNPCC-related families in Poland, we genotyped 463 probands from HNPCC and HNPCC-related families, and 5,496 controls for 4 CHEK2 alleles (1100delC, IVS2+1G>A, del5395, I157T). All 463 probands were screened for mutations in the HNPCC-related genes MSH2, MLH1 and MSH6. A positive association was observed for HNPCC-related cancer and the I157T missense CHEK2 mutation (OR = 1.7; p = 0.007), but not for the truncating alleles (OR = 1.0; p = 1.0). The association with the I157T was seen both for the 117 cases who fulfill Amsterdam criteria (OR = 1.9; p = 0.1) and for the 346 cases who do not fulfill the criteria (OR = 1.6; p = 0.03). One hundred forty-five of the 463 families had a mutation in MSH2, MLH1 or MSH6 (MMR-positive families). A positive association between the CHEK2 I157T mutation and HNPCC-related cancer was observed only for MMR-negative cases (OR = 2.1; p = 0.0004), but not for MMR-positive cases (OR = 0.8; p = 0.9). The association with I157T was particularly strong for MMR-negative cases with familial colorectal cancer (2 or more first-degree relatives affected) (OR = 2.5; p < 0.0001). We conclude that the I157T variant of CHEK2 increases the risk of colorectal cancer among MMR-negative, HNPCC/HNPCC-related families in Poland.
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http://dx.doi.org/10.1002/ijc.25003DOI Listing
June 2010

Pathologist and HIV--are safe autopsies possible?

Pol J Pathol 2003 ;54(2):143-6

Department of Hygiene and Epidemiology, Pomeranian Academy of Medicine, Szczecin.

Pathologists are at particularly high risk for blood contamination and skin injuries, so they are vulnerable to blood borne pathogens, like HIV. This article describes the first and the only one documented case of occupational HIV transmission in the world concerning American pathologist. The factors increasing the risk of contracting infection during the autopsy on the patient who has died of AIDS are considered. World-known recommendations to follow in such autopsy are described. The importance of compliance with universal precautions and the necessity of knowledge of the post-exposure prophylaxis are pointed as a way to avoid HIV infection.
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November 2003
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