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1. Interobserver variability in the assessment of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative invasive breast carcinoma influences the association with pathological complete response: the IVITA study

Author

Van Bockstal, Mieke R., François, Aline, Altinay, Serdar, Arnould, Laurent, Balkenhol, Maschenka, Broeckx, Glenn, Burguès, Octavio, Colpaert, Cecile, Dedeurwaerdere, Franceska, Dessauvagie, Benjamin, Duwel, Valérie, Floris, Giuseppe, Fox, Stephen, Gerosa, Clara, Hastir, Delfyne, Jaffer, Shabnam, Kurpershoek, Eline, Lacroix-Triki, Magali, Laka, Andoni, Lambein, Kathleen, MacGrogan, Gaëtan Marie, Marchiò, Caterina, Martin Martinez, Maria-Dolores, Nofech-Mozes, Sharon, Peeters, Dieter, Ravarino, Alberto, Reisenbichler, Emily, Resetkova, Erika, Sanati, Souzan, Schelfhout, Anne-Marie, Schelfhout, Vera, Shaaban, Abeer, Sinke, Renata, Stanciu-Pop, Claudia M., van Deurzen, Carolien H.M., Van de Vijver, Koen K., Van Rompuy, Anne-Sophie, Vincent-Salomon, Anne, Wen, Hannah Y., Wong, Serena, Bouzin, Caroline, and Galant, Christine

Published
2021
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2. Interobserver variability in upfront dichotomous histopathological assessment of ductal carcinoma in situ of the breast: the DCISion study

Author

Dano, Hélène, Altinay, Serdar, Arnould, Laurent, Bletard, Noella, Colpaert, Cecile, Dedeurwaerdere, Franceska, Dessauvagie, Benjamin, Duwel, Valérie, Floris, Giuseppe, Fox, Stephen, Gerosa, Clara, Jaffer, Shabnam, Kurpershoek, Eline, Lacroix-Triki, Magali, Laka, Andoni, Lambein, Kathleen, MacGrogan, Gaëtan Marie, Marchió, Caterina, Martinez, Dolores Martin, Nofech-Mozes, Sharon, Peeters, Dieter, Ravarino, Alberto, Reisenbichler, Emily, Resetkova, Erika, Sanati, Souzan, Schelfhout, Anne-Marie, Schelfhout, Vera, Shaaban, Abeer M., Sinke, Renata, Stanciu-Pop, Claudia Maria, Stobbe, Claudia, van Deurzen, Carolien H.M., Van de Vijver, Koen, Van Rompuy, Anne-Sophie, Verschuere, Stephanie, Vincent-Salomon, Anne, Wen, Hannah, Bouzin, Caroline, Galant, Christine, and Van Bockstal, Mieke R.

Published
2020
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3. Epidemiology of native kidney disease in Flanders

Author

Laurens, Wim, Deleersnijder, Dries, Dendooven, Amélie, Lerut, Evelyne, De Vriese, An, Dejagere, Tom, Helbert, Mark, Hellemans, Rachel, Koshy, Priyanka, Maes, Bart, Pipeleers, Lissa, Van Craenenbroeck, Amaryllis H, Van Laecke, Steven, Vande Walle, Johan, Coutteneye, Marie M, De Meester, Johan, Sprangers, Ben, De Rycke, Anja, Bogaert, Anne-Marie, Woestenburg, Annemie, Denys, Bart, Peeters, Domien, Vanbelleghem, Hilde, Donck, Jan, Scharpé, Johan, De Clippeleir, Nele, Vanparys, Joris, Meyvis, Karen, Vandepitte, Kurt, Reyns, Liza-Maria, Verresen, Luc, Decupere, Marc, Zeegers, Miranda, Neirynck, Nathalie, Bernaert, Pascale, Lemahieu, Wim, Levtchenko, Elena, Karamaria, Sevasti, Van Hoeck, Koen, Trouet, Dominique, Mauel, Reiner, Hoorens, Anne, Van Dorpe, Jo, Praet, Marleen, Geers, Caroline, Roskams, Tania, Aydin, Selda, Siozopoulou, Vasiliki, Schelfhout, Anne-Marie, De Raeve, Hendrik, Steenkiste, Edwin, Dedeurwaerdere, Francesca, Dalle, Ignace, Cokelaere, Kristof, Deloose, Stijn, De Paepe, Pascale, Van Eyken, Peter, FCGG collaborative group, [missing], Pathology, Faculty of Sciences and Bioengineering Sciences, Faculty of Medicine and Pharmacy, Clinical sciences, Medicine and Pharmacy academic/administration, Nephrology, and FCGG Collaborative Group

Subjects
PRIMARY GLOMERULONEPHRITIS, Transplantation, Science & Technology, Epidemiology, Biopsy, Urology & Nephrology, registry, DIAGNOSIS, FREQUENCY, native kidney, PATHOLOGY, Nephrology, REGISTRY, Medicine and Health Sciences, incidence, biopsy, epidemiology, RENAL BIOPSY, pathology, Human medicine, observational, Life Sciences & Biomedicine
Abstract

Background The Flemish Collaborative Glomerulonephritis Group (FCGG) registry is the first population-based native kidney biopsy registry in Flanders, Belgium. In this first analysis, we report on patient demographics, frequency distribution and incidence rate of biopsied kidney disease in adults in Flanders. Methods From January 2017 to December 2019, a total of 2054 adult first native kidney biopsies were included. A ‘double diagnostic coding’ strategy was used, in which every biopsy sample received a histopathological and final clinical diagnosis. Frequency distribution and incidence rate of both diagnoses were reported and compared with other European registries. Results The median age at biopsy was 61.1 years (interquartile range, 46.1–71.7); male patients were more prevalent (62.1%) and biopsy incidence rate was 129.3 per million persons per year. Immunoglobulin A nephropathy was the most frequently diagnosed kidney disease (355 biopsies, 17.3% of total) with a similar frequency as in previously published European registries. The frequency of tubulointerstitial nephritis (220 biopsies, 10.7%) and diabetic kidney disease (154 biopsies, 7.5%) was remarkably higher, which may be attributed to changes in disease incidence as well as biopsy practices. Discordances between histopathological and final clinical diagnoses were noted and indicate areas for improvement in diagnostic coding systems. Conclusions The FCGG registry, with its ‘double diagnostic coding’ strategy, provides useful population-based epidemiological data on a large Western European population and allows subgroup selection for future research.

Published
2022

4. Inter-observer agreement for the histological diagnosis of invasive lobular breast carcinoma

Author

Christgen, Matthias, Kandt, Leonie Donata, Antonopoulos, Wiebke, Bartels, Stephan, Van Bockstal, Mieke R., Bredt, Martin, Brito, Maria Jose, Christgen, Henriette, Colpaert, Cecile, Cserni, Bálint, Cserni, Gábor, Daemmrich, Maximilian E., Danebrock, Raihanatou, Dedeurwaerdere, Franceska, van Deurzen, Carolien H.M., Erber, Ramona, Fathke, Christine, Feist, Henning, Fiche, Maryse, Gonzalez, Claudia Aura, ter Hoeve, Natalie D., Kooreman, Loes, Krech, Till, Kristiansen, Glen, Kulka, Janina, Laenger, Florian, Lafos, Marcel, Lehmann, Ulrich, Martin-Martinez, Maria Dolores, Mueller, Sophie, Pelz, Enrico, Raap, Mieke, Ravarino, Alberto, Reineke-Plaass, Tanja, Schaumann, Nora, Schelfhout, Anne Marie, De Schepper, Maxim, Schlue, Jerome, Van de Vijver, Koen, Waelput, Wim, Wellmann, Axel, Graeser, Monika, Gluz, Oleg, Kuemmel, Sherko, Nitz, Ulrike, Harbeck, Nadia, Desmedt, Christine, Floris, Giuseppe, Derksen, Patrick W.B., van Diest, Paul J., Vincent-Salomon, Anne, Kreipe, Hans, Christgen, Matthias, Kandt, Leonie Donata, Antonopoulos, Wiebke, Bartels, Stephan, Van Bockstal, Mieke R., Bredt, Martin, Brito, Maria Jose, Christgen, Henriette, Colpaert, Cecile, Cserni, Bálint, Cserni, Gábor, Daemmrich, Maximilian E., Danebrock, Raihanatou, Dedeurwaerdere, Franceska, van Deurzen, Carolien H.M., Erber, Ramona, Fathke, Christine, Feist, Henning, Fiche, Maryse, Gonzalez, Claudia Aura, ter Hoeve, Natalie D., Kooreman, Loes, Krech, Till, Kristiansen, Glen, Kulka, Janina, Laenger, Florian, Lafos, Marcel, Lehmann, Ulrich, Martin-Martinez, Maria Dolores, Mueller, Sophie, Pelz, Enrico, Raap, Mieke, Ravarino, Alberto, Reineke-Plaass, Tanja, Schaumann, Nora, Schelfhout, Anne Marie, De Schepper, Maxim, Schlue, Jerome, Van de Vijver, Koen, Waelput, Wim, Wellmann, Axel, Graeser, Monika, Gluz, Oleg, Kuemmel, Sherko, Nitz, Ulrike, Harbeck, Nadia, Desmedt, Christine, Floris, Giuseppe, Derksen, Patrick W.B., van Diest, Paul J., Vincent-Salomon, Anne, and Kreipe, Hans

Published
2022

5. Inter-observer agreement for the histological diagnosis of invasive lobular breast carcinoma

Author

Pathologie Groep Derksen, Cancer, Pathologie, Christgen, Matthias, Kandt, Leonie Donata, Antonopoulos, Wiebke, Bartels, Stephan, Van Bockstal, Mieke R, Bredt, Martin, Brito, Maria Jose, Christgen, Henriette, Colpaert, Cecile, Cserni, Bálint, Cserni, Gábor, Daemmrich, Maximilian E, Danebrock, Raihanatou, Dedeurwaerdere, Franceska, van Deurzen, Carolien Hm, Erber, Ramona, Fathke, Christine, Feist, Henning, Fiche, Maryse, Gonzalez, Claudia Aura, Ter Hoeve, Natalie D, Kooreman, Loes, Krech, Till, Kristiansen, Glen, Kulka, Janina, Laenger, Florian, Lafos, Marcel, Lehmann, Ulrich, Martin-Martinez, Maria Dolores, Mueller, Sophie, Pelz, Enrico, Raap, Mieke, Ravarino, Alberto, Reineke-Plaass, Tanja, Schaumann, Nora, Schelfhout, Anne-Marie, De Schepper, Maxim, Schlue, Jerome, Van de Vijver, Koen, Waelput, Wim, Wellmann, Axel, Graeser, Monika, Gluz, Oleg, Kuemmel, Sherko, Nitz, Ulrike, Harbeck, Nadia, Desmedt, Christine, Floris, Giuseppe, Derksen, Patrick Wb, van Diest, Paul J, Vincent-Salomon, Anne, Kreipe, Hans, Pathologie Groep Derksen, Cancer, Pathologie, Christgen, Matthias, Kandt, Leonie Donata, Antonopoulos, Wiebke, Bartels, Stephan, Van Bockstal, Mieke R, Bredt, Martin, Brito, Maria Jose, Christgen, Henriette, Colpaert, Cecile, Cserni, Bálint, Cserni, Gábor, Daemmrich, Maximilian E, Danebrock, Raihanatou, Dedeurwaerdere, Franceska, van Deurzen, Carolien Hm, Erber, Ramona, Fathke, Christine, Feist, Henning, Fiche, Maryse, Gonzalez, Claudia Aura, Ter Hoeve, Natalie D, Kooreman, Loes, Krech, Till, Kristiansen, Glen, Kulka, Janina, Laenger, Florian, Lafos, Marcel, Lehmann, Ulrich, Martin-Martinez, Maria Dolores, Mueller, Sophie, Pelz, Enrico, Raap, Mieke, Ravarino, Alberto, Reineke-Plaass, Tanja, Schaumann, Nora, Schelfhout, Anne-Marie, De Schepper, Maxim, Schlue, Jerome, Van de Vijver, Koen, Waelput, Wim, Wellmann, Axel, Graeser, Monika, Gluz, Oleg, Kuemmel, Sherko, Nitz, Ulrike, Harbeck, Nadia, Desmedt, Christine, Floris, Giuseppe, Derksen, Patrick Wb, van Diest, Paul J, Vincent-Salomon, Anne, and Kreipe, Hans

Published
2022

6. Clinicopathological characteristics and disease chronicity in native kidney biopsies in Flanders

Author

Deleersnijder, Dries, Laurens, Wim, De Meester, Johan, Cleenders, Evert, Dendooven, Amélie, Lerut, Evelyne, De Vriese, An, Dejagere, Tom, Helbert, Mark, Hellemans, Rachel, Koshy, Priyanka, Maes, Bart, Pipeleers, Lissa, Van Craenenbroeck, Amaryllis H, Van Laecke, Steven, Vande Walle, Johan, Couttenye, Marie M, Meeus, Gert, Sprangers, Ben, De Rycke, Anja, Bogaert, Anne-Marie, Woestenburg, Annemie, Denys, Bart, Peeters, Domien, Vanbelleghem, Hilde, Donck, Jan, Scharpé, Johan, De Clippeleir, Nele, Colson, Ann, Meyvis, Karen, Vandepitte, Kurt, Reyns, Liza-Maria, Peeters, Jacques, Decupere, Marc, Zeegers, Miranda, Neirynck, Nathalie, Bernaert, Pascale, Lemahieu, Wim, Knops, Noël, Levtchenko, Elena, Karamaria, Sevasti, Van Hoeck, Koen, Trouet, Dominique, Maul, Reiner, Hoorens, Anne, Van Dorpe, Jo, Praet, Marleen, Geers, Caroline, Roskams, Tania, Aydin, Selda, Siozopoulou, Vasiliki, Schelfhout, Anne-Marie, De Raeve, Hendrik, Steenkiste, Edwin, Dedeurwaerdere, Francesca, Dalle, Ignace, Cokelaere, Kristof, Deloose, Stijn, De Paepe, Pascale, Van Eyken, Peter, FCGG collaborative group, [missing], Deleersnijder, Dries, Laurens, Wim, De Meester, Johan, Cleenders, Evert, Dendooven, Amelie, Lerut, Evelyne, De Vriese, An S., DEJAGERE, Tom, Helbert, Mark, Hellemans, Rachel, Koshy, Priyanka, Maes, Bart, Pipeleers, Lissa, Van Craenenbroeck, Amaryllis H., Van Laecke, Steven, Vande Walle, Johan, Couttenye, Marie M., Meeus, Gert, SPRANGERS, Ben, Pathology, Faculty of Sciences and Bioengineering Sciences, Faculty of Medicine and Pharmacy, Internal Medicine, Clinical sciences, Nephrology, and FCGG Collaborative Group

Subjects
Transplantation, OUTCOMES, Science & Technology, chronicity, kidney biopsy, Urology & Nephrology, registry, DIAGNOSIS, FREQUENCY, CLASSIFICATION, PATHOLOGY, GLOMERULONEPHRITIS, Nephrology, Medicine and Health Sciences, EPIDEMIOLOGY, RENAL BIOPSY, epidemiology, MCCS, Human medicine, NEPHRITIS, Life Sciences & Biomedicine
Abstract

Lay Summary The Flemish Collaborative Glomerulonephritis Group (FCGG) registry collects information on patients that undergo kidney biopsy in the region of Flanders in Belgium. The registry summarizes the underlying diagnoses in patients that present with symptoms of kidney disease (e.g. blood and/or protein in the urine or decreased kidney function). Additionally, the registry also collects information on the degree of chronic damage on kidney biopsy. This is important because chronic damage may lead to kidney failure. From 2017 until 2019, a total of 2054 adult biopsies were analyzed, while chronic damage could be analyzed in 898 biopsies. We found that the underlying causes of severe kidney disease were similar to studies performed in other European countries. Importantly, we found that increasing age, reduced kidney function and certain diagnoses are associated with more chronic damage on kidney biopsy. This information may be useful to doctors in clinical practice, in both Belgium and Europe. Background The Flemish Collaborative Glomerulonephritis Group (FCGG) registry provides complete population data on kidney disease epidemiology in the region of Flanders (Belgium), as it captures all native kidney biopsies performed in its population of 6.5 million inhabitants. Methods From 2017 until 2019, 2054 adult kidney biopsies were included from 26 nephrology centers (one biopsy per patient). Data on nephrotic and nephritic syndrome were available in 1992 and 2026 biopsies, respectively. In a subgroup of 898 biopsies containing >= 10 glomeruli from 2018 to 2019, disease chronicity was graded using the Mayo Clinic Chronicity Score (MCCS). The association between clinical variables and MCCS was determined using simple and multiple linear regression models. Results Nephrotic syndrome (present in 378 patients, 19.0%) was most frequently caused by minimal change disease in younger patients (18-44 years), membranous nephropathy in older patients (45-74 years) and amyloidosis in the elderly (>75 years). Nephritic syndrome (present in 421 patients, 20.8%) was most frequently caused by immunoglobulin A nephropathy (IgAN) in younger patients (18-64 years) and ANCA-associated vasculitis (AAV) in older patients (>64 years). AAV and IgAN were the most frequent underlying diagnoses in biopsies in which crescents were identified. In multivariable analysis, acute and chronic kidney disease and diagnoses of diabetic kidney disease, nephrosclerosis and hyperoxaluria/hypercalcemic nephropathy were associated with the highest MCCS increases. Conclusions The FCGG registry validates data from previous Western European registries and provides a snapshot of disease chronicity in the whole biopsied Flemish population. D.D. is supported by a PhD Fellowship grant fundamental research from the Research Foundation Flanders (F.W.O., grant number 11L5622N). B.S. is a senior clinical investigator of The Research Foundation Flanders (F.W.O., grant number 1 842 919 N). The FCGG registry is funded by the Nederlandstalige Belgische Vereniging voor Nefrologie (NBVN). The authors wish to thank all collaborating nephrologists in Flanders and Brussels and responsible persons at the data entry centers (Elsie De Man, Sabine Verhofstede, Ben Sprangers) for their participation in the FCGG registry. The FCGG registry was initiated in collaboration with the Nederlandstalige Belgische Vereniging voor Nefrologie (NBVN), the organization that represents the majority of nephrologists in the region of Flanders. The study was approved by the Ethical Committee of the University Hospitals Leuven (study reference S59182) and local committees of all participating centers.

Published
2022

7. Inter‐observer agreement for the histological diagnosis of invasive lobular breast carcinoma

Author

Christgen, Matthias, primary, Kandt, Leonie Donata, additional, Antonopoulos, Wiebke, additional, Bartels, Stephan, additional, Bockstal, Mieke R, additional, Bredt, Martin, additional, Brito, Maria Jose, additional, Christgen, Henriette, additional, Colpaert, Cecile, additional, Cserni, Bálint, additional, Cserni, Gábor, additional, Daemmrich, Maximilian E, additional, Danebrock, Raihanatou, additional, Dedeurwaerdere, Franceska, additional, Deurzen, Carolien HM, additional, Erber, Ramona, additional, Fathke, Christine, additional, Feist, Henning, additional, Fiche, Maryse, additional, Gonzalez, Claudia Aura, additional, Hoeve, Natalie D, additional, Kooreman, Loes, additional, Krech, Till, additional, Kristiansen, Glen, additional, Kulka, Janina, additional, Laenger, Florian, additional, Lafos, Marcel, additional, Lehmann, Ulrich, additional, Martin‐Martinez, Maria Dolores, additional, Mueller, Sophie, additional, Pelz, Enrico, additional, Raap, Mieke, additional, Ravarino, Alberto, additional, Reineke‐Plaass, Tanja, additional, Schaumann, Nora, additional, Schelfhout, Anne‐Marie, additional, Schepper, Maxim, additional, Schlue, Jerome, additional, Van de Vijver, Koen, additional, Waelput, Wim, additional, Wellmann, Axel, additional, Graeser, Monika, additional, Gluz, Oleg, additional, Kuemmel, Sherko, additional, Nitz, Ulrike, additional, Harbeck, Nadia, additional, Desmedt, Christine, additional, Floris, Giuseppe, additional, Derksen, Patrick WB, additional, Diest, Paul J, additional, Vincent‐Salomon, Anne, additional, and Kreipe, Hans, additional

Published
2021
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8. Interobserver variability in the assessment of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative invasive breast carcinoma influences the association with pathological complete response: the IVITA study.

Author

UCL - (MGD) Service d'anatomie pathologique, UCL - SSS/IREC/MONT - Pôle Mont Godinne, Van Bockstal, Mieke R, François, Aline, Altinay, Serdar, Arnould, Laurent, Balkenhol, Maschenka, Broeckx, Glenn, Burguès, Octavio, Colpaert, Cecile, Dedeurwaerdere, Franceska, Dessauvagie, Benjamin, Duwel, Valérie, Floris, Giuseppe, Fox, Stephen, Gerosa, Clara, Hastir, Delfyne, Jaffer, Shabnam, Kurpershoek, Eline, Lacroix-Triki, Magali, Laka, Andoni, Lambein, Kathleen, MacGrogan, Gaëtan Marie, Marchiò, Caterina, Martin Martinez, Maria-Dolores, Nofech-Mozes, Sharon, Peeters, Dieter, Ravarino, Alberto, Reisenbichler, Emily, Resetkova, Erika, Sanati, Souzan, Schelfhout, Anne-Marie, Schelfhout, Vera, Shaaban, Abeer, Sinke, Renata, Stanciu-Pop, Claudia, van Deurzen, Carolien H M, Van de Vijver, Koen K, Van Rompuy, Anne-Sophie, Vincent-Salomon, Anne, Wen, Hannah Y, Wong, Serena, Bouzin, Caroline, Galant, Christine, UCL - (MGD) Service d'anatomie pathologique, UCL - SSS/IREC/MONT - Pôle Mont Godinne, Van Bockstal, Mieke R, François, Aline, Altinay, Serdar, Arnould, Laurent, Balkenhol, Maschenka, Broeckx, Glenn, Burguès, Octavio, Colpaert, Cecile, Dedeurwaerdere, Franceska, Dessauvagie, Benjamin, Duwel, Valérie, Floris, Giuseppe, Fox, Stephen, Gerosa, Clara, Hastir, Delfyne, Jaffer, Shabnam, Kurpershoek, Eline, Lacroix-Triki, Magali, Laka, Andoni, Lambein, Kathleen, MacGrogan, Gaëtan Marie, Marchiò, Caterina, Martin Martinez, Maria-Dolores, Nofech-Mozes, Sharon, Peeters, Dieter, Ravarino, Alberto, Reisenbichler, Emily, Resetkova, Erika, Sanati, Souzan, Schelfhout, Anne-Marie, Schelfhout, Vera, Shaaban, Abeer, Sinke, Renata, Stanciu-Pop, Claudia, van Deurzen, Carolien H M, Van de Vijver, Koen K, Van Rompuy, Anne-Sophie, Vincent-Salomon, Anne, Wen, Hannah Y, Wong, Serena, Bouzin, Caroline, and Galant, Christine

Abstract

High stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC) are associated with pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Histopathological assessment of sTILs in TNBC biopsies is characterized by substantial interobserver variability, but it is unknown whether this affects its association with pCR. Here, we aimed to investigate the degree of interobserver variability in an international study, and its impact on the relationship between sTILs and pCR. Forty pathologists assessed sTILs as a percentage in digitalized biopsy slides, originating from 41 TNBC patients who were treated with NAC followed by surgery. Pathological response was quantified by the MD Anderson Residual Cancer Burden (RCB) score. Intraclass correlation coefficients (ICCs) were calculated per pathologist duo and Bland-Altman plots were constructed. The relation between sTILs and pCR or RCB class was investigated. The ICCs ranged from -0.376 to 0.947 (mean: 0.659), indicating substantial interobserver variability. Nevertheless, high sTILs scores were significantly associated with pCR for 36 participants (90%), and with RCB class for eight participants (20%). Post hoc sTILs cutoffs at 20% and 40% resulted in variable associations with pCR. The sTILs in TNBC with RCB-II and RCB-III were intermediate to those of RCB-0 and RCB-I, with lowest sTILs observed in RCB-I. However, the limited number of RCB-I cases precludes any definite conclusions due to lack of power, and this observation therefore requires further investigation. In conclusion, sTILs are a robust marker for pCR at the group level. However, if sTILs are to be used to guide the NAC scheme for individual patients, the observed interobserver variability might substantially affect the chance of obtaining a pCR. Future studies should determine the 'ideal' sTILs threshold, and attempt to fine-tune the patient selection for sTILs-based de-escalation of NAC regimens. At present, there

Published
2021

9. Interobserver variability in the assessment of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative invasive breast carcinoma influences the association with pathological complete response: the IVITA study.

Author

UCL - SSS/IREC/MORF - Pôle de Morphologie, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service d'anatomie pathologique, UCL - (MGD) Service d'anatomie pathologique, Van Bockstal, Mieke, Francois, Aline, Altinay, Serdar, Arnould, Laurent, Balkenhol, Maschenka, Broeckx, Glenn, Burguès, Octavio, Colpaert, Cecile, Dedeurwaerdere, Franceska, Dessauvagie, Benjamin, Duwel, Valérie, Floris, Giuseppe, Fox, Stephen, Gerosa, Clara, Hastir, Delfyne, Jaffer, Shabnam, Kurpershoek, Eline, Lacroix-Triki, Magali, Laka, Andoni, Lambein, Kathleen, MacGrogan, Gaëtan Marie, Marchiò, Caterina, Martin Martinez, Maria-Dolores, Nofech-Mozes, Sharon, Peeters, Dieter, Ravarino, Alberto, Reisenbichler, Emily, Resetkova, Erika, Sanati, Souzan, Schelfhout, Anne-Marie, Schelfhout, Vera, Shaaban, Abeer, Sinke, Renata, Stanciu-Pop, Claudia Maria, van Deurzen, Carolien H M, Van de Vijver, Koen K, Van Rompuy, Anne-Sophie, Vincent-Salomon, Anne, Wen, Hannah Y, Wong, Serena, Bouzin, Caroline, Galant, Christine, UCL - SSS/IREC/MORF - Pôle de Morphologie, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service d'anatomie pathologique, UCL - (MGD) Service d'anatomie pathologique, Van Bockstal, Mieke, Francois, Aline, Altinay, Serdar, Arnould, Laurent, Balkenhol, Maschenka, Broeckx, Glenn, Burguès, Octavio, Colpaert, Cecile, Dedeurwaerdere, Franceska, Dessauvagie, Benjamin, Duwel, Valérie, Floris, Giuseppe, Fox, Stephen, Gerosa, Clara, Hastir, Delfyne, Jaffer, Shabnam, Kurpershoek, Eline, Lacroix-Triki, Magali, Laka, Andoni, Lambein, Kathleen, MacGrogan, Gaëtan Marie, Marchiò, Caterina, Martin Martinez, Maria-Dolores, Nofech-Mozes, Sharon, Peeters, Dieter, Ravarino, Alberto, Reisenbichler, Emily, Resetkova, Erika, Sanati, Souzan, Schelfhout, Anne-Marie, Schelfhout, Vera, Shaaban, Abeer, Sinke, Renata, Stanciu-Pop, Claudia Maria, van Deurzen, Carolien H M, Van de Vijver, Koen K, Van Rompuy, Anne-Sophie, Vincent-Salomon, Anne, Wen, Hannah Y, Wong, Serena, Bouzin, Caroline, and Galant, Christine

Abstract

High stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC) are associated with pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Histopathological assessment of sTILs in TNBC biopsies is characterized by substantial interobserver variability, but it is unknown whether this affects its association with pCR. Here, we aimed to investigate the degree of interobserver variability in an international study, and its impact on the relationship between sTILs and pCR. Forty pathologists assessed sTILs as a percentage in digitalized biopsy slides, originating from 41 TNBC patients who were treated with NAC followed by surgery. Pathological response was quantified by the MD Anderson Residual Cancer Burden (RCB) score. Intraclass correlation coefficients (ICCs) were calculated per pathologist duo and Bland-Altman plots were constructed. The relation between sTILs and pCR or RCB class was investigated. The ICCs ranged from -0.376 to 0.947 (mean: 0.659), indicating substantial interobserver variability. Nevertheless, high sTILs scores were significantly associated with pCR for 36 participants (90%), and with RCB class for eight participants (20%). Post hoc sTILs cutoffs at 20% and 40% resulted in variable associations with pCR. The sTILs in TNBC with RCB-II and RCB-III were intermediate to those of RCB-0 and RCB-I, with lowest sTILs observed in RCB-I. However, the limited number of RCB-I cases precludes any definite conclusions due to lack of power, and this observation therefore requires further investigation. In conclusion, sTILs are a robust marker for pCR at the group level. However, if sTILs are to be used to guide the NAC scheme for individual patients, the observed interobserver variability might substantially affect the chance of obtaining a pCR. Future studies should determine the 'ideal' sTILs threshold, and attempt to fine-tune the patient selection for sTILs-based de-escalation of NAC regimens. At present, there

Published
2021

13. Abstract P5-02-04: Upfront dichotomous histopathological assessment of ductal carcinoma in situ of the breast to reduce inter-observer variability: The DCISion study

Author

Van Bockstal, Mieke Rosalie, primary, Dano, Hélène, additional, Altinay, Serdar, additional, Arnould, Laurent, additional, Bletard, Noella, additional, Colpaert, Cecile, additional, Dedeurwaerdere, Franceska, additional, Dessauvagie, Benjamin, additional, Duwel, Valérie, additional, Floris, Giuseppe, additional, Fox, Stephen, additional, Gerosa, Clara, additional, Jaffer, Shabnam, additional, Kurpershoek, Eline, additional, Lacroix-Triki, Magali, additional, Laka, Andoni, additional, Lambein, Kathleen, additional, MacGrogan, Gaëtan Marie, additional, Marchió, Caterina, additional, Martinez, Dolores Martin, additional, Nofech-Mozes, Sharon, additional, Peeters, Dieter, additional, Ravarino, Alberto, additional, Reisenbichler, Emily, additional, Resetkova, Erika, additional, Sanati, Souzan, additional, Schelfhout, Anne-Marie, additional, Schelfhout, Vera, additional, Shaaban, Abeer M, additional, Sinke, Renata, additional, Stanciu-Pop, Claudia Maria, additional, Stobbe, Claudia, additional, van Deurzen, Carolien HM, additional, de Vijver, Koen Van, additional, Van Rompuy, Anne-Sophie, additional, Verschuere, Stephanie, additional, Vincent-Salomon, Anne, additional, Wen, Hannah, additional, Bouzin, Caroline, additional, and Galant, Christine, additional

Published
2020
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18. The neu-protein and breast cancer.

Author

Potter, Christian and Schelfhout, Anne-Marie

Abstract

The neu-protein is overexpressed in about 20% of invasive duct cell carcinomas of the breast. The only reliable sign for neu-overexpression by immunohistochemistry is membrane staining. Its overexpression is correlated with decreased overall survival and disease free survival due to increased metastatic activity of neu-overexpressing tumour cells. This increased metastatic potential is a consequence of the motility enhancing activity of the neu-protein, which is exclusively expressed on pseudopodia, and to a lesser extent of its growth stimulating effect. From a clinical point of view, the assessment of neu-overexpression in breast cancer might become a useful tool in the future treatment of patients by chemotherapy, since patients whose tumour shows neu-overexpression benefit from higher doses of chemotherapy. The molecule plays a key role in the pathogenesis of Paget's disease of the breast. A chemotactic factor which is secreted by epidermal keratinocytes attracts the Paget cells to spread into the epidermis and acts via the neu-protein. In ductal carcinoma in situ, the combination of neu-overexpression and large cell type is highly correlated with extent of disease and therefore neu-overexpression might be a predictive marker for recurrence of disease after tumour resection. [ABSTRACT FROM AUTHOR]

Published
1995
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19. Inter-observer agreement for the histological diagnosis of invasive lobular breast carcinoma.

Author

Christgen M, Kandt LD, Antonopoulos W, Bartels S, Van Bockstal MR, Bredt M, Brito MJ, Christgen H, Colpaert C, Cserni B, Cserni G, Daemmrich ME, Danebrock R, Dedeurwaerdere F, van Deurzen CH, Erber R, Fathke C, Feist H, Fiche M, Gonzalez CA, Ter Hoeve ND, Kooreman L, Krech T, Kristiansen G, Kulka J, Laenger F, Lafos M, Lehmann U, Martin-Martinez MD, Mueller S, Pelz E, Raap M, Ravarino A, Reineke-Plaass T, Schaumann N, Schelfhout AM, De Schepper M, Schlue J, Van de Vijver K, Waelput W, Wellmann A, Graeser M, Gluz O, Kuemmel S, Nitz U, Harbeck N, Desmedt C, Floris G, Derksen PW, van Diest PJ, Vincent-Salomon A, and Kreipe H

Subjects
Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Female, Humans, Immunohistochemistry, Observer Variation, Breast Neoplasms diagnosis, Breast Neoplasms genetics, Breast Neoplasms metabolism, Carcinoma, Lobular diagnosis, Carcinoma, Lobular genetics
Abstract

Invasive lobular breast carcinoma (ILC) is the second most common breast carcinoma (BC) subtype and is mainly driven by loss of E-cadherin expression. Correct classification of BC as ILC is important for patient treatment. This study assessed the degree of agreement among pathologists for the diagnosis of ILC. Two sets of hormone receptor (HR)-positive/HER2-negative BCs were independently reviewed by participating pathologists. In set A (61 cases), participants were provided with hematoxylin/eosin (HE)-stained sections. In set B (62 cases), participants were provided with HE-stained sections and E-cadherin immunohistochemistry (IHC). Tumor characteristics were balanced. Participants classified specimens as non-lobular BC versus mixed BC versus ILC. Pairwise inter-observer agreement and agreement with a pre-defined reference diagnosis were determined with Cohen's kappa statistics. Subtype calls were correlated with molecular features, including CDH1/E-cadherin mutation status. Thirty-five pathologists completed both sets, providing 4,305 subtype calls. Pairwise inter-observer agreement was moderate in set A (median κ = 0.58, interquartile range [IQR]: 0.48-0.66) and substantial in set B (median κ = 0.75, IQR: 0.56-0.86, p < 0.001). Agreement with the reference diagnosis was substantial in set A (median κ = 0.67, IQR: 0.57-0.75) and almost perfect in set B (median κ = 0.86, IQR: 0.73-0.93, p < 0.001). The median frequency of CDH1/E-cadherin mutations in specimens classified as ILC was 65% in set A (IQR: 56-72%) and 73% in set B (IQR: 65-75%, p < 0.001). Cases with variable subtype calls included E-cadherin-positive ILCs harboring CDH1 missense mutations, and E-cadherin-negative ILCs with tubular elements and focal P-cadherin expression. ILCs with trabecular growth pattern were often misclassified as non-lobular BC in set A but not in set B. In conclusion, subtyping of BC as ILC achieves almost perfect agreement with a pre-defined reference standard, if assessment is supported by E-cadherin IHC. CDH1 missense mutations associated with preserved E-cadherin protein expression, E- to P-cadherin switching in ILC with tubular elements, and trabecular ILC were identified as potential sources of discordant classification., (© 2021 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland & John Wiley & Sons, Ltd.)

Published
2022
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