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  1. AU="Petronilho, Sara"
  2. AU="Ordóñez, Raquel"
  3. AU="Mulvaney, Robert"
  4. AU="Amarin, Z"
  5. AU="Vadlin, S"
  6. AU="Erin E. Michalak"
  7. AU="Cassidy, Caitlin A"
  8. AU="Veronica Davalos"
  9. AU="Koba, Wade R"
  10. AU="Cui, Hongyan"
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  1. Article ; Online: Cytohistological correlation in serous effusions using the newly proposed International System for Reporting Serous Fluid Cytopathology: Experience of an oncological center.

    Lobo, Cláudia / Costa, João / Petronilho, Sara / Monteiro, Paula / Leça, Luís / Schmitt, Fernando

    Diagnostic cytopathology

    2020  Volume 49, Issue 5, Page(s) 596–605

    Abstract: Background: Cytological analysis is part of the initial etiological evaluation of serous effusions. The newly proposed International System for Reporting Serous Fluid Cytopathology (ISRSFC) aims to standardize reporting.: Methods: All pleural and ... ...

    Abstract Background: Cytological analysis is part of the initial etiological evaluation of serous effusions. The newly proposed International System for Reporting Serous Fluid Cytopathology (ISRSFC) aims to standardize reporting.
    Methods: All pleural and peritoneal effusion samples admitted for cytological analysis at our institution between 2012 and 2016, and pericardial effusion samples admitted between 2008 and 2018, were reviewed and reclassified according to the ISRSFC. Risk of malignancy (ROM) and performance parameters were calculated.
    Results: 1496 pleural effusion samples were reclassified: 12(0.8%) non-diagnostic (ND), 944(63.1%) negative for malignancy (NFM), 9(0.6%) atypia of undetermined significance (AUS), 54(3.6%) suspicious of malignancy (SFM) and 477(31.9%) malignant (M). 64 pericardial effusion samples were reclassified: 23(35.9%) NFM, 1(1.6%) AUS, 4(6.3%) SFM and 36(56.2%) M. 763 peritoneal effusion samples were reclassified: 5(0.7%) ND, 457(59.9%) NFM, 12(1.6%) AUS, 37(4.8%) SFM and 252(33%) M. The ROM was, respectively, for each of the aforementioned categories, 57.1%, 23.9%, 50%, 76.2%, 100% in pleural effusions, 100%, 26.3%, 62.5%, 91.7%, 100% in peritoneal effusions and 0% for NFM, 0% for AUS and 100% for M in pericardial effusions. Sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy were, respectively, 61.6%, 100%, 100%, 73.3%, 81.3% for pleural, 100%, 100%, 100%, 100%, 100% for pericardial and 61.2%, 100%, 100%, 70%, 79.7% for peritoneal effusion samples.
    Conclusion: Serous effusion cytology has a high specificity and positive predictive value and a modest sensitivity and negative predictive value, supporting its role in confirming the diagnosis of malignancy. The ISRSFC will increase standardization and reproducibility in reporting, leading to improved clinical decision-making.
    MeSH term(s) Adolescent ; Adult ; Aged ; Aged, 80 and over ; Ascitic Fluid/pathology ; Child ; Child, Preschool ; Cytodiagnosis/methods ; Cytodiagnosis/standards ; Female ; Humans ; Male ; Middle Aged ; Neoplasms/diagnosis ; Pericardial Effusion/pathology ; Pleural Effusion, Malignant/pathology ; Retrospective Studies ; Sensitivity and Specificity ; Young Adult
    Language English
    Publishing date 2020-04-27
    Publishing country United States
    Document type Journal Article ; Observational Study
    ZDB-ID 632710-2
    ISSN 1097-0339 ; 8755-1039
    ISSN (online) 1097-0339
    ISSN 8755-1039
    DOI 10.1002/dc.24440
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: ALK+ large B cell lymphoma presenting as multiple bowel-obstructing, cytokeratin-positive tumours.

    Petronilho, Sara / Gournay, Viviane / Tauziede-Espariat, Arnault / Pina, Héloïse / Pecriaux, Adrien / Drieux, Fanny / Poullot, Elsa / Briere, Josette / Lechapt, Emmanuèle / Gaulard, Phillippe

    Histopathology

    2022  Volume 80, Issue 7, Page(s) 1128–1130

    MeSH term(s) Humans ; Keratins ; Ki-1 Antigen ; Lymphoma, Large B-Cell, Diffuse/diagnosis ; Lymphoma, Large B-Cell, Diffuse/pathology ; Lymphoma, Large-Cell, Anaplastic/pathology ; Receptor Protein-Tyrosine Kinases
    Chemical Substances Ki-1 Antigen ; Keratins (68238-35-7) ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1)
    Language English
    Publishing date 2022-03-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 131914-0
    ISSN 1365-2559 ; 0309-0167
    ISSN (online) 1365-2559
    ISSN 0309-0167
    DOI 10.1111/his.14635
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Apoptosis induction and cell cycle arrest of pladienolide B in erythroleukemia cell lines.

    Jorge, Joana / Petronilho, Sara / Alves, Raquel / Coucelo, Margarida / Gonçalves, Ana Cristina / Nascimento Costa, José Manuel / Sarmento-Ribeiro, Ana Bela

    Investigational new drugs

    2019  Volume 38, Issue 2, Page(s) 369–377

    Abstract: Splicing of pre-mRNA into functional mRNA, carried out by the spliceosome, represents a crucial step in eukaryotic gene expression. Mutations and other deregulation in some of the spliceosome components have been identified in multiple pathologies, ... ...

    Abstract Splicing of pre-mRNA into functional mRNA, carried out by the spliceosome, represents a crucial step in eukaryotic gene expression. Mutations and other deregulation in some of the spliceosome components have been identified in multiple pathologies, including hematological malignancies. In this context, we evaluated the therapeutic potential of a splicing inhibitor, Pladienolide B (Pla-B), in two erythroleukemia cell lines. HEL and K562 cell lines were incubated with increasing doses of Pla-B in single and daily administration. Cell viability and density were evaluated using trypan blue assay. Flow cytometry was used to evaluate cell death, cell cycle, and caspase activity. NGS analysis was performed to assess the mutational status of 4 splicing-related genes (SF3B1, U2AF1, ZRSR2 and SRSF2). Expression levels of SF3B1 and unspliced DNAJB1 were evaluated by qPCR. Pla-B significantly decreased the viability and proliferation of both cell lines in time, dose, administration schedule, and cell line-dependent manner. HEL cells were more sensible to Pla-B (IC
    MeSH term(s) Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Cell Cycle Checkpoints/drug effects ; Cell Line, Tumor ; Cell Survival/drug effects ; Epoxy Compounds/pharmacology ; HSP40 Heat-Shock Proteins/genetics ; Humans ; Leukemia, Erythroblastic, Acute/drug therapy ; Leukemia, Erythroblastic, Acute/genetics ; Macrolides/pharmacology ; Phosphoproteins/genetics ; RNA Splicing Factors/genetics
    Chemical Substances Antineoplastic Agents ; DNAJB1 protein, human ; Epoxy Compounds ; HSP40 Heat-Shock Proteins ; Macrolides ; Phosphoproteins ; RNA Splicing Factors ; SF3B1 protein, human ; pladienolide B
    Language English
    Publishing date 2019-05-31
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 604895-x
    ISSN 1573-0646 ; 0167-6997
    ISSN (online) 1573-0646
    ISSN 0167-6997
    DOI 10.1007/s10637-019-00796-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Prognostic Value of Histone Modifying Enzyme EZH2 in RCHOP-Treated Diffuse Large B-Cell Lymphoma and High Grade B-Cell Lymphoma.

    Petronilho, Sara / Sequeira, José Pedro / Paulino, Sofia / Lopes, Paula / Lisboa, Susana / Chacim, Sérgio / Lobo, João / Teixeira, Manuel / Jerónimo, Carmen / Henrique, Rui

    Journal of personalized medicine

    2021  Volume 11, Issue 12

    Abstract: Background: DLBCL represent a heterogeneous group of aggressive diseases. High grade B-cell lymphomas (HGBCL) were recently individualized from DLBCL as a discrete diagnostic entity due to their worse prognosis. Currently, although most patients are ... ...

    Abstract Background: DLBCL represent a heterogeneous group of aggressive diseases. High grade B-cell lymphomas (HGBCL) were recently individualized from DLBCL as a discrete diagnostic entity due to their worse prognosis. Currently, although most patients are successfully treated with RCHOP regimens, 1/3 will either not respond or ultimately relapse. Alterations in histone modifying enzymes have emerged as the most common alterations in DLBCL, but their role as prognostic biomarkers is controversial. We aimed to ascertain the prognostic value of EZH2 immunoexpression in RCHOP-treated DLBCL and HGBCL.
    Results: We performed a retrospective cohort study including 125 patients with RCHOP-treated DLBCL or HGBCL. EZH2 expression levels did not differ between diagnostic groups or between DLBCL-NOS molecular groups. We found no associations between EZH2 expression levels and outcome, including in the subgroup analysis (GC versus non-GC). Nonetheless, EZH2/BCL2 co-expression was significantly associated with worse outcome (event free survival and overall survival).
    Conclusion: Although EZH2 mutations are almost exclusively found in GC-DLBCL, we found similar EZH2 expression levels in both DLBCL-NOS molecular groups, suggesting non-mutational mechanisms of EZH2 deregulation. These findings suggest that the use of EZH2 antagonists might be extended to non-GC DLBCL patients with clinical benefit. EZH2/BCL2 co-expression was associated with a worse outcome.
    Language English
    Publishing date 2021-12-18
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662248-8
    ISSN 2075-4426
    ISSN 2075-4426
    DOI 10.3390/jpm11121384
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Performance of DNA methylation-based biomarkers in the cervical cancer screening program of northern Portugal: A feasibility study.

    Salta, Sofia / Maia-Moço, Leonardo / Estevão-Pereira, Helena / Sequeira, José Pedro / Vieira, Renata / Bartosch, Carla / Petronilho, Sara / Monteiro, Paula / Sousa, Ana / Baldaque, Inês / Rodrigues, Jéssica / Sousa, Hugo / Tavares, Fernando / Henrique, Rui / Jerónimo, Carmen

    International journal of cancer

    2021  Volume 149, Issue 11, Page(s) 1916–1925

    Abstract: Cervical cancer remains a health concern. Effective screening programs are critical to reduce the incidence and mortality. High-risk HPV (hr-HPV) testing as primary screening tool discloses high sensitivity but suboptimal specificity. Adequate triage ... ...

    Abstract Cervical cancer remains a health concern. Effective screening programs are critical to reduce the incidence and mortality. High-risk HPV (hr-HPV) testing as primary screening tool discloses high sensitivity but suboptimal specificity. Adequate triage tests to reduce unnecessary colposcopy referrals and overdiagnosis/overtreatment are crucial. Hence, we aimed to validate a panel of DNA methylation-based markers as triage test for women hr-HPV+ in the population-based Regional Cervical Cancer Screening Program of Northern Portugal. Firstly, CADM1, MAL, FAM19A4 and hsa-miR124-2 promoter methylation levels were assessed by multiplex QMSP in a testing set of 402 FFPE tissue samples (159 normal samples and 243 cervical lesions, including 39 low-grade intraepithelial squamous lesions [LSIL], 59 high-grade intraepithelial squamous lesions [HSIL] and 145 cancerous lesions). Then, preliminary validation was performed in 125 hr-HPV+ cervical scrapes (including 59 normal samples, 30 LSIL, 34 HSIL and 2 cancerous lesions). Higher MAL
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Cervical Intraepithelial Neoplasia/diagnosis ; Cervical Intraepithelial Neoplasia/epidemiology ; Cervical Intraepithelial Neoplasia/genetics ; Cervical Intraepithelial Neoplasia/pathology ; DNA Methylation ; Early Detection of Cancer/methods ; Feasibility Studies ; Female ; Humans ; Middle Aged ; Papillomaviridae/isolation & purification ; Papillomavirus Infections/diagnosis ; Papillomavirus Infections/genetics ; Papillomavirus Infections/pathology ; Portugal ; Promoter Regions, Genetic ; Sensitivity and Specificity ; Triage ; Uterine Cervical Neoplasms/diagnosis ; Uterine Cervical Neoplasms/genetics ; Uterine Cervical Neoplasms/pathology ; Young Adult
    Chemical Substances Biomarkers, Tumor
    Language English
    Publishing date 2021-09-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218257-9
    ISSN 1097-0215 ; 0020-7136
    ISSN (online) 1097-0215
    ISSN 0020-7136
    DOI 10.1002/ijc.33778
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: E-cadherin clone 36 nuclear staining dictates adverse disease outcome in lobular breast cancer patients.

    Lobo, João / Petronilho, Sara / Newell, Amy Hanlon / Coach, Julia / Harlow, Greg / Cruz, Andréia / Lopes, Paula / Antunes, Luís / Bai, Isaac / Walker, Espen / Henrique, Rui

    Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

    2019  Volume 32, Issue 11, Page(s) 1574–1586

    Abstract: Breast cancer is a heterogeneous disease and additional biomarkers for individually predicting patient outcomes are needed. Aberrant membrane E-cadherin immunoexpression has been demonstrated in lobular breast cancer. Also, E-cadherin nuclear staining ... ...

    Abstract Breast cancer is a heterogeneous disease and additional biomarkers for individually predicting patient outcomes are needed. Aberrant membrane E-cadherin immunoexpression has been demonstrated in lobular breast cancer. Also, E-cadherin nuclear staining has been reported, associating with prognosis in various tumors. Here, we explore whether membrane or nuclear staining of E-cadherin has the potential to dictate prognosis of patients with lobular breast cancer. We selected a cohort of 285 consecutively diagnosed lobular breast cancer patients and performed immunohistochemistry for E-cadherin (clones 36, EP700Y, and NCH38) and P-cadherin (clone 56C1) in representative formalin-fixed paraffin-embedded blocks. All patients were female, HER2-negative and surgically treated in a single institution. Survival curves were computed by Kaplan-Meier analysis. Hazard ratios and respective 95% confidence intervals were estimated using Cox regression models. Statistical significance was set at p < 0.05. Nuclear staining for E-cadherin clone 36 was frequent (35%), contrarily to other antibodies tested. Negative correlation was found between nuclear and membrane E-cadherin clone 36 immunostaining (r
    MeSH term(s) Aged ; Antigens, CD/analysis ; Biomarkers, Tumor/analysis ; Breast Neoplasms/mortality ; Breast Neoplasms/pathology ; Cadherins/analysis ; Carcinoma, Lobular/mortality ; Carcinoma, Lobular/pathology ; Cell Nucleus/metabolism ; Female ; Humans ; Middle Aged ; Prognosis ; Retrospective Studies
    Chemical Substances Antigens, CD ; Biomarkers, Tumor ; CDH1 protein, human ; Cadherins
    Language English
    Publishing date 2019-06-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 645073-8
    ISSN 1530-0285 ; 0893-3952
    ISSN (online) 1530-0285
    ISSN 0893-3952
    DOI 10.1038/s41379-019-0294-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Assessment of HER2 Protein Overexpression and Gene Amplification in Renal Collecting Duct Carcinoma: Therapeutic Implication.

    Costantini, Manuela / Amoreo, Carla Azzurra / Torregrossa, Liborio / Alì, Greta / Munari, Enrico / Jeronimo, Carmen / Henrique, Rui / Petronilho, Sara / Capitanio, Umberto / Lucianò, Roberta / Suardi, Nazareno / Landi, Maria Teresa / Anceschi, Umberto / Brassetti, Aldo / Fazio, Vito Michele / Gallucci, Michele / Simone, Giuseppe / Sentinelli, Steno / Poeta, Maria Luana

    Cancers

    2020  Volume 12, Issue 11

    Abstract: Collecting duct carcinoma (CDC) is rare and aggressive histology of kidney cancers. Although different therapeutic approaches have been tested, the 2-year survival remains very poor. Since CDC exhibits overlapping features with urothelial carcinoma, the ... ...

    Abstract Collecting duct carcinoma (CDC) is rare and aggressive histology of kidney cancers. Although different therapeutic approaches have been tested, the 2-year survival remains very poor. Since CDC exhibits overlapping features with urothelial carcinoma, the analysis of shared molecular alterations could provide new insights into the understanding of this rare disease and also therapeutic options. We collected 26 CDC cases, and we assessed HER2 protein expression by immunohistochemistry (IHC) and gene amplification by fluorescence in-situ hybridization (FISH) according to 2018 ASCO/CAP HER2-testing recommendations. Six out of twenty-six (23%) tumors showed HER2 positive staining. In particular, 3+ score was present in 2/6 cases (33%), 2+ in 3/6 cases (50%) and 1+ in 1/6 cases (17%). The 6 HER2+ tumors were also analyzed by FISH to assess gene copy number. One out of six CDC with IHC 3+ was also HER2 amplified, showing an average HER2 copy number ≥4.0 (10.85) and a HER2/CEP17 ratio ≥ (5.63), while the 5/6 cases were HER2 negative. Based on the 2018 ASCO/CAP guidelines overall, 2/26 CDC cases (8%) were HER2+. The present study provides evidence for testing, in future studies, HER2 to assess its clinical value as a novel target for the treatment of this highly malignant cancer.
    Language English
    Publishing date 2020-11-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers12113345
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Clinical Significance of ARID1A and ANXA1 in HER-2 Positive Breast Cancer.

    Silva-Oliveira, Rita / Pereira, Filipa Ferreira / Petronilho, Sara / Martins, Ana Teresa / Lameirinhas, Ana / Constâncio, Vera / Caldas-Ribeiro, Inês / Salta, Sofia / Lopes, Paula / Antunes, Luís / Castro, Fernando / de Sousa, Susana Palma / Henrique, Rui / Jerónimo, Carmen

    Journal of clinical medicine

    2020  Volume 9, Issue 12

    Abstract: Background: trastuzumab is considered the standard of care for human epidermal growth factor receptor-2 (HER-2+) breast cancer patients. Regardless of the benefits of its use, many early-stage patients eventually recur, and usually, the disease ... ...

    Abstract Background: trastuzumab is considered the standard of care for human epidermal growth factor receptor-2 (HER-2+) breast cancer patients. Regardless of the benefits of its use, many early-stage patients eventually recur, and usually, the disease progresses within a year. Since about half of the HER-2+ patients do not respond to trastuzumab, new biomarkers of prognosis and prediction are warranted to allow a better patient stratification. Annexin A1 (ANXA1) was previously reported to contribute to trastuzumab resistance through AKT activation. An association between adenine thymine-rich interactive domain 1A (ARID1A) loss and ANXA1 upregulation was also previously suggested by others.
    Methods: in this study, we examined tissue samples from 215 HER-2+ breast cancer patients to investigate the value of ARID1A and ANXA1 protein levels in trastuzumab response prediction and patient outcome. Expression of ARID1A and ANXA1 were assessed by immunohistochemistry.
    Results: contrary to what was expected, no inverse association was found between ARID1A and ANXA1 expression. HER-2+ (non-luminal) tumours displayed higher ANXA1 expression than luminal B-like (HER-2+) tumours. Concerning trastuzumab resistance, ARID1A and ANXA1 proteins did not demonstrate predictive value as biomarkers. Nevertheless, an association was depicted between ANXA1 expression and breast cancer mortality and relapse.
    Conclusions: overall, our results suggest that ANXA1 may be a useful prognostic marker in HER-2+ patients. Additionally, its ability to discriminate between HER-2+ (non-luminal) and luminal B-like (HER-2+) patients might assist in patient stratification regarding treatment strategy.
    Language English
    Publishing date 2020-12-02
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662592-1
    ISSN 2077-0383
    ISSN 2077-0383
    DOI 10.3390/jcm9123911
    Database MEDical Literature Analysis and Retrieval System OnLINE

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