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Article ; Online: scAbsolute: measuring single-cell ploidy and replication status.

Schneider, Michael P / Cullen, Amy E / Pangonyte, Justina / Skelton, Jason / Major, Harvey / Van Oudenhove, Elke / Garcia, Maria J / Chaves Urbano, Blas / Piskorz, Anna M / Brenton, James D / Macintyre, Geoff / Markowetz, Florian

Genome biology

2024 Volume 25, Issue 1, Page(s) 62

Abstract: Cancer cells often exhibit DNA copy number aberrations and can vary widely in their ploidy. Correct estimation of the ploidy of single-cell genomes is paramount for downstream analysis. Based only on single-cell DNA sequencing information, scAbsolute ... ...

Abstract	Cancer cells often exhibit DNA copy number aberrations and can vary widely in their ploidy. Correct estimation of the ploidy of single-cell genomes is paramount for downstream analysis. Based only on single-cell DNA sequencing information, scAbsolute achieves accurate and unbiased measurement of single-cell ploidy and replication status, including whole-genome duplications. We demonstrate scAbsolute's capabilities using experimental cell multiplets, a FUCCI cell cycle expression system, and a benchmark against state-of-the-art methods. scAbsolute provides a robust foundation for single-cell DNA sequencing analysis across different technologies and has the potential to enable improvements in a number of downstream analyses.
MeSH term(s)	Benchmarking ; Cell Cycle/genetics ; Cell Division ; Ploidies ; Sequence Analysis, DNA
Language	English
Publishing date	2024-03-04
Publishing country	England
Document type	Journal Article
ZDB-ID	2040529-7
ISSN	1474-760X ; 1474-760X
ISSN (online)	1474-760X
ISSN	1474-760X
DOI	10.1186/s13059-024-03204-y
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Article: Comparison of SCORE-predicted risk of death due to cardiovascular events in women before and after menopause.

Piskorz, Anna / Brzostek, Tomasz

Przeglad menopauzalny = Menopause review

2015 Volume 14, Issue 3, Page(s) 168–172

Abstract: Introduction: Approximately 55% of women in Europe die from cardiovascular events, mostly as a result of coronary diseases and cerebral stroke. There is a 10-year shift in the cardiovascular risk between women and men. The risk in a 55-year-old female ... ...

Abstract	Introduction: Approximately 55% of women in Europe die from cardiovascular events, mostly as a result of coronary diseases and cerebral stroke. There is a 10-year shift in the cardiovascular risk between women and men. The risk in a 55-year-old female patient is similar to that of a 45-year-old man, thus the risk among women increases rapidly around the age of 50, when menopause prevails to occur. The purpose of the study was to assess and compare the SCORE-predicted risk of a fatal cardiovascular incident in pre- and postmenopausal women. Material and methods: The cross-sectional study was conducted as part of community nursing practice. It covered 219 women - inhabitants of Krakow, aged from 30 to 65, without clinically validated cardiovascular diseases of arteriosclerotic and/or diabetic origin, who volunteered to take part in the study. The group was divided into three subgroups: K1 - menstruating women (n = 113), K2a - women after natural menopause (n = 88), and K2b - women after surgical menopause (n = 18). The study made use of a lifestyle questionnaire, which concerned the social and economic status, and lifestyle habits including tobacco smoking. Arterial blood pressure was measured, and total cholesterol concentration in blood (mmol/l) was recorded. Results: A high (≥ 5%) level of the SCORE risk was discovered in 14.3% of postmenopausal women, as compared to 0.9% in the group of menstruating women. An average risk of a fatal cardiovascular incident during the following 10 years was significantly higher among women from groups K2a (2.61%) and K2b (2.32%) as compared to K1 - menstruating women (0.38%). No difference was, however, discovered between groups of naturally (K2a) and surgically menopausal women (K2b). Conclusions: A significantly higher risk of SCORE-predicted death caused by a cardiovascular incident, as compared to the group of women in the premenopausal period, is characteristic of women in the postmenopausal period.
Language	English
Publishing date	2015-09-30
Publishing country	Poland
Document type	Journal Article
ZDB-ID	2596140-8
ISSN	2299-0038 ; 1643-8876
ISSN (online)	2299-0038
ISSN	1643-8876
DOI	10.5114/pm.2015.54340
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Article ; Online: EGFR-activated myofibroblasts promote metastasis of pancreatic cancer.

Mucciolo, Gianluca / Araos Henríquez, Joaquín / Jihad, Muntadher / Pinto Teles, Sara / Manansala, Judhell S / Li, Wenlong / Ashworth, Sally / Lloyd, Eloise G / Cheng, Priscilla S W / Luo, Weike / Anand, Akanksha / Sawle, Ashley / Piskorz, Anna / Biffi, Giulia

Cancer cell

2023 Volume 42, Issue 1, Page(s) 101–118.e11

Abstract: Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. Cancer-associated fibroblasts (CAFs) are recognized potential therapeutic targets, but poor understanding of these heterogeneous cell populations has limited the development of effective ... ...

Abstract	Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. Cancer-associated fibroblasts (CAFs) are recognized potential therapeutic targets, but poor understanding of these heterogeneous cell populations has limited the development of effective treatment strategies. We previously identified transforming growth factor beta (TGF-β) as a main driver of myofibroblastic CAFs (myCAFs). Here, we show that epidermal growth factor receptor/Erb-B2 receptor (EGFR/ERBB2) signaling is induced by TGF-β in myCAFs through an autocrine process mediated by amphiregulin. Inhibition of this EGFR/ERBB2-signaling network in PDAC organoid-derived cultures and mouse models differentially impacts distinct CAF subtypes, providing insights into mechanisms underpinning their heterogeneity. Remarkably, EGFR-activated myCAFs promote PDAC metastasis in mice, unmasking functional significance in myCAF heterogeneity. Finally, analyses of other cancer datasets suggest that these processes might operate in other malignancies. These data provide functional relevance to myCAF heterogeneity and identify a candidate target for preventing tumor invasion in PDAC.
MeSH term(s)	Mice ; Animals ; Myofibroblasts/pathology ; Pancreatic Neoplasms/drug therapy ; Carcinoma, Pancreatic Ductal/drug therapy ; Signal Transduction ; Transforming Growth Factor beta ; Tumor Microenvironment
Chemical Substances	Transforming Growth Factor beta
Language	English
Publishing date	2023-12-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2078448-X
ISSN	1878-3686 ; 1535-6108
ISSN (online)	1878-3686
ISSN	1535-6108
DOI	10.1016/j.ccell.2023.12.002
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Article ; Online: Immunohistochemistry and Next-generation Sequencing Are Complementary Tests in Identifying PTEN Abnormality in Endometrial Carcinoma Biopsies.

Wang, Linyuan / Piskorz, Anna / Bosse, Tjalling / Jimenez-Linan, Mercedes / Rous, Brian / Gilks, C Blake / Brenton, James D / Singh, Naveena / Köbel, Martin

International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists

2021 Volume 41, Issue 1, Page(s) 12–19

Abstract: PTEN plays a central role in the pathogenesis of endometrial carcinoma. Previous studies reported a high interobserver reproducibility for the interpretation of PTEN immunohistochemistry (IHC). However, PTEN IHC and its interpretation remain challenging ... ...

Abstract	PTEN plays a central role in the pathogenesis of endometrial carcinoma. Previous studies reported a high interobserver reproducibility for the interpretation of PTEN immunohistochemistry (IHC). However, PTEN IHC and its interpretation remain challenging during laboratory practice. The purpose of this study was to reevaluate PTEN IHC pattern in direct comparison to next-generation sequencing in identifying PTEN abnormality. IHC and tagged-amplicon next-generation sequencing PTEN sequencing was performed on 182 endometrial carcinoma biopsy/curetting samples from five centers (Barts, Calgary, Cambridge, Leiden, and Vancouver). Sensitivity, specificity and accuracy of PTEN IHC to predict loss of function PTEN mutations were calculated. Abnormalities of PTEN in association with histotype and molecular subtype were assessed. A total of 5 PTEN IHC patterns were recorded: absent, subclonal loss, equivocal, reduced (relative to internal control) and retained. The absence of PTEN IHC has a sensitivity of 75.4% (95% confidence interval: 62.7-85.5%), a specificity of 84.6% (95% confidence interval: 76.2%-90.9%), and accuracy of 81.2% (95% confidence interval: 74.4%-86.9%) in predicting loss of function PTEN mutation. PTEN abnormality by complementary interpretation of both assays was present in 91.9% of endometrial endometrioid carcinoma, grade 1, and significantly higher in endometrial endometrioid carcinomas of all grades compared with endometrial serous carcinoma (80.0% vs. 19.4%, P<0.0001). PTEN abnormalities are common across all molecular subtypes of endometrioid carcinomas. Our data support the use of ancillary PTEN IHC for diagnostic purposes in endometrial neoplasms. However, for clinical trial design complementary testing of both IHC and sequencing of PTEN should be considered to assess the PTEN status in endometrial carcinomas.
MeSH term(s)	Biopsy ; Carcinoma, Endometrioid/diagnosis ; Carcinoma, Endometrioid/metabolism ; Carcinoma, Endometrioid/pathology ; Cohort Studies ; Endometrial Neoplasms/diagnosis ; Endometrial Neoplasms/metabolism ; Endometrial Neoplasms/pathology ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Immunohistochemistry ; Loss of Function Mutation ; Molecular Typing ; Mutation ; Neoplasm Grading ; PTEN Phosphohydrolase/genetics ; PTEN Phosphohydrolase/metabolism ; Reproducibility of Results ; Sequence Analysis, DNA
Chemical Substances	PTEN Phosphohydrolase (EC 3.1.3.67) ; PTEN protein, human (EC 3.1.3.67)
Language	English
Publishing date	2021-03-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	604859-6
ISSN	1538-7151 ; 0277-1691
ISSN (online)	1538-7151
ISSN	0277-1691
DOI	10.1097/PGP.0000000000000763
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Article ; Online: High-grade serous ovarian carcinoma organoids as models of chromosomal instability.

Vias, Maria / Morrill Gavarró, Lena / Sauer, Carolin M / Sanders, Deborah A / Piskorz, Anna M / Couturier, Dominique-Laurent / Ballereau, Stéphane / Hernando, Bárbara / Schneider, Michael P / Hall, James / Correia-Martins, Filipe / Markowetz, Florian / Macintyre, Geoff / Brenton, James D

eLife

2023 Volume 12

Abstract: High-grade serous ovarian carcinoma (HGSOC) is the most genomically complex cancer, characterized by ... ...

Abstract	High-grade serous ovarian carcinoma (HGSOC) is the most genomically complex cancer, characterized by ubiquitous
MeSH term(s)	Humans ; Female ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Mutation ; Genomics ; Chromosomal Instability ; Organoids
Language	English
Publishing date	2023-05-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.83867
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Article: Identification of Tissue-Resident Natural Killer and T Lymphocytes with Anti-Tumor Properties in Ascites of Ovarian Cancer Patients.

Bernson, Elin / Huhn, Oisín / Karlsson, Veronika / Hawkes, Delia / Lycke, Maria / Cazzetta, Valentina / Mikulak, Joanna / Hall, James / Piskorz, Anna M / Portuesi, Rosalba / Vitobello, Domenico / Fiamengo, Barbara / Siesto, Gabriele / Horowitz, Amir / Ghadially, Hormas / Mavilio, Domenico / Brenton, James D / Sundfeldt, Karin / Colucci, Francesco

Cancers

2023 Volume 15, Issue 13

Abstract: Women with ovarian cancer have limited therapy options, with immunotherapy being unsatisfactory for a large group of patients. Tumor cells spread from the ovary or the fallopian tube into the abdominal cavity, which is commonly accompanied with massive ... ...

Abstract	Women with ovarian cancer have limited therapy options, with immunotherapy being unsatisfactory for a large group of patients. Tumor cells spread from the ovary or the fallopian tube into the abdominal cavity, which is commonly accompanied with massive ascites production. The ascites represents a unique peritoneal liquid tumor microenvironment with the presence of both tumor and immune cells, including cytotoxic lymphocytes. We characterized lymphocytes in ascites from patients with high-grade serous ovarian cancer. Our data reveal the presence of NK and CD8
Language	English
Publishing date	2023-06-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15133362
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Article ; Online: p53 immunohistochemistry is an accurate surrogate for TP53 mutational analysis in endometrial carcinoma biopsies.

Singh, Naveena / Piskorz, Anna M / Bosse, Tjalling / Jimenez-Linan, Mercedes / Rous, Brian / Brenton, James D / Gilks, C Blake / Köbel, Martin

The Journal of pathology

2020 Volume 250, Issue 3, Page(s) 336–345

Abstract: TP53 mutations are considered a surrogate biomarker of the serous-like 'copy number high' molecular subtype of endometrial carcinoma (EC). In ovarian carcinoma, p53 immunohistochemistry (IHC) accurately reflects mutational status with almost 100% ... ...

Abstract	TP53 mutations are considered a surrogate biomarker of the serous-like 'copy number high' molecular subtype of endometrial carcinoma (EC). In ovarian carcinoma, p53 immunohistochemistry (IHC) accurately reflects mutational status with almost 100% specificity but its performance in EC has not been established. This study tested whether p53 IHC reliably predicts TP53 mutations identified by next-generation sequencing (NGS) in EC biopsy samples for all ECs and as part of a molecular classification algorithm after exclusion of cases harbouring mismatch repair defects (MMRd) or pathogenic DNA polymerase epsilon exonuclease domain mutations (POLEmut). A secondary aim assessed inter-laboratory variability in p53 IHC. From a total of 207 cases from five centres (37-49 cases per centre), p53 IHC carried out at a central reference laboratory was compared with local IHC (n = 164) and curated tagged-amplicon NGS TP53 sequencing results (n = 177). Following consensus review, local and central p53 IHC results were concordant in 156/164 (95.1%) tumours. Discordant results were attributable to both interpretive and technical differences in staining between the local and central laboratories. When results were considered as any mutant pattern versus wild-type pattern staining, however, there was disagreement between local and central review in only one case. The concordance between p53 IHC and TP53 mutation was 155/168 (92.3%) overall, and 117/123 (95.1%) after excluding MMRd and POLEmut EC. Three (3/6) discordant results were in serous carcinomas with complete absence of p53 staining but no detectable TP53 mutation. Subclonal mutant p53 IHC expression was observed in 9/177 (5.1%) cases, of which four were either MMRd or POLEmut. Mutant pattern p53 IHC was observed in 63/63 (100%) serous carcinomas that were MMR-proficient/POLE exonuclease domain wild-type. Optimised p53 IHC performs well as a surrogate test for TP53 mutation in EC biopsies, demonstrates excellent inter-laboratory reproducibility, and has high clinical utility for molecular classification algorithms in EC. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
MeSH term(s)	Carcinoma, Endometrioid/genetics ; Carcinoma, Endometrioid/metabolism ; Carcinoma, Endometrioid/pathology ; Cystadenocarcinoma, Serous/genetics ; Cystadenocarcinoma, Serous/metabolism ; Cystadenocarcinoma, Serous/pathology ; DNA Mutational Analysis ; Endometrial Neoplasms/genetics ; Endometrial Neoplasms/metabolism ; Endometrial Neoplasms/pathology ; Female ; Humans ; Immunohistochemistry ; Mutation ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism
Chemical Substances	Tumor Suppressor Protein p53
Language	English
Publishing date	2020-01-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3119-7
ISSN	1096-9896 ; 0022-3417
ISSN (online)	1096-9896
ISSN	0022-3417
DOI	10.1002/path.5375
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Article ; Online: Selected Socio-Demographic and Occupational Factors of Burnout Syndrome in Nurses Employed in Medical Facilities in Małopolska-Preliminary Results.

Nowacka, Anna / Piskorz, Anna / Wolfshaut-Wolak, Renata / Piątek, Jadwiga / Gniadek, Agnieszka

International journal of environmental research and public health

2018 Volume 15, Issue 10

Abstract: The study examined the relationship between socio-demographic and occupational factors and the level of occupational burnout using the dimensions of emotional exhaustion (EE), depersonalization (DEP), and personal accomplishment (PA). It examined 560 ... ...

Abstract	The study examined the relationship between socio-demographic and occupational factors and the level of occupational burnout using the dimensions of emotional exhaustion (EE), depersonalization (DEP), and personal accomplishment (PA). It examined 560 nurses working in hospitals and primary healthcare units. We used: Maslach Burnout Inventory and a questionnaire including socio-demographic (sex, age, marital status, education, parental status) and occupational (period of employment, workplace, managerial functions, additional employment) factors. An average respondent was 38.13 (SD = 10.16) and had a BA degree (56.0%). The respondents reported average values of the EE (22.8), a low level of DEP (Me = 6), and a low PA (27.63). Nurses working on the intensive care unit had a chance of a high level of DEP that was 75% lower (OR = 0.25, 95% CI = 0.13⁻0.50) than nurses working in conservative treatment units. Additional employment increased the risk of a high level of DEP (OR = 2.86, 95% CI = 1.70⁻4.84). The chance of low PA was 64% lower in the case of nurse managers (OR = 0.36, 95% CI = 0.13⁻0.998) than other nurses. Education, period of employment, additional employment, and managerial position had a significant influence on the level of occupational burnout. An analysis of nurses' work overload and additional employment can be an interesting research area.
MeSH term(s)	Adult ; Burnout, Professional/etiology ; Burnout, Professional/psychology ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Nurses/psychology ; Nursing Staff, Hospital/psychology ; Poland ; Primary Care Nursing ; Risk Factors ; Socioeconomic Factors ; Surveys and Questionnaires
Language	English
Publishing date	2018-09-21
Publishing country	Switzerland
Document type	Journal Article ; Multicenter Study ; Observational Study ; Research Support, Non-U.S. Gov't
ISSN	1660-4601
ISSN (online)	1660-4601
DOI	10.3390/ijerph15102083
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Article ; Online: Author Correction: The copy number and mutational landscape of recurrent ovarian high-grade serous carcinoma.

Nature communications

2023 Volume 14, Issue 1, Page(s) 5992

Language	English
Publishing date	2023-09-26
Publishing country	England
Document type	Published Erratum
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-41611-0
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Article ; Online: The copy number and mutational landscape of recurrent ovarian high-grade serous carcinoma.

Nature communications

2023 Volume 14, Issue 1, Page(s) 4387

Abstract: The drivers of recurrence and resistance in ovarian high grade serous carcinoma remain unclear. We investigate the acquisition of resistance by collecting tumour biopsies from a cohort of 276 women with relapsed ovarian high grade serous carcinoma in the ...

Abstract	The drivers of recurrence and resistance in ovarian high grade serous carcinoma remain unclear. We investigate the acquisition of resistance by collecting tumour biopsies from a cohort of 276 women with relapsed ovarian high grade serous carcinoma in the BriTROC-1 study. Panel sequencing shows close concordance between diagnosis and relapse, with only four discordant cases. There is also very strong concordance in copy number between diagnosis and relapse, with no significant difference in purity, ploidy or focal somatic copy number alterations, even when stratified by platinum sensitivity or prior chemotherapy lines. Copy number signatures are strongly correlated with immune cell infiltration, whilst diagnosis samples from patients with primary platinum resistance have increased rates of CCNE1 and KRAS amplification and copy number signature 1 exposure. Our data show that the ovarian high grade serous carcinoma genome is remarkably stable between diagnosis and relapse and acquired chemotherapy resistance does not select for common copy number drivers.
MeSH term(s)	Humans ; Female ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; DNA Copy Number Variations/genetics ; Neoplasm Recurrence, Local/genetics ; Mutation ; Cystadenocarcinoma, Serous/drug therapy ; Cystadenocarcinoma, Serous/genetics ; Cystadenocarcinoma, Serous/pathology
Language	English
Publishing date	2023-07-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-39867-7
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