Immunohistochemical method and histopathology judging for the systemic synuclein sampling study (S4)

Thomas G. Beach; Geidy E. Serrano; Thomas Kremer; Marta Canamero; Sebastian Dziadek; Hadassah Sade; Pascal Derkinderen; Anne Gaëlle Corbillé; Franck Letournel; David G. Munoz; Charles L. White; Julie Schneider; John F. Crary; Lucia I. Sue; Charles H. Adler; Michael J. Glass; Anthony J. Intorcia; Jessica E. Walker; Tatiana Foroud; Christopher S. Coffey; Dixie Ecklund; Holly Riss; Jennifer Goßmann; Fatima König; Catherine M. Kopil; Vanessa Arnedo; Lindsey Riley; Carly Linder; Kuldip D. Dave; Danna Jennings; John Seibyl; Brit Mollenhauer; Lana Chahine

doi:10.1093/jnen/nly056

Immunohistochemical method and histopathology judging for the systemic synuclein sampling study (S4)

Thomas G. Beach, Geidy E. Serrano, Thomas Kremer, Marta Canamero, Sebastian Dziadek, Hadassah Sade, Pascal Derkinderen, Anne Gaëlle Corbillé, Franck Letournel, David G. Munoz, Charles L. White, Julie Schneider, John F. Crary, Lucia I. Sue, Charles H. Adler, Michael J. Glass, Anthony J. Intorcia, Jessica E. Walker, Tatiana Foroud, Christopher S. CoffeyDixie Ecklund, Holly Riss, Jennifer Goßmann, Fatima König, Catherine M. Kopil, Vanessa Arnedo, Lindsey Riley, Carly Linder, Kuldip D. Dave, Danna Jennings, John Seibyl, Brit Mollenhauer, Lana Chahine

Neurology

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

Immunohistochemical (IHC) α-synuclein (Asyn) pathology in peripheral biopsies may be a biomarker of Parkinson disease (PD). The multi-center Systemic Synuclein Sampling Study (S4) is evaluating IHC Asyn pathology within skin, colon and submandibular gland biopsies from 60 PD and 20 control subjects. Asyn pathology is being evaluated by a blinded panel of specially trained neuropathologists. Preliminary work assessed 2 candidate immunoperoxidase methods using a set of PD and control autopsy-derived sections from formalin-fixed, paraffin-embedded blocks of the 3 tissues. Both methods had 100% specificity; one, utilizing the 5C12 monoclonal antibody, was more sensitive in skin (67% vs 33%), and was chosen for further use in S4. Four trainee neuropathologists were trained to perform S4 histopathology readings; in subsequent testing, their scoring was compared to that of the trainer neuropathologist on both glass slides and digital images. Specificity and sensitivity were both close to 100% with all readers in all tissue types on both glass slides and digital images except for skin, where sensitivity averaged 75% with digital images and 83.5% with glass slides. Semiquantitative (0-3) density score agreement between trainees and trainer averaged 67% for glass slides and 62% for digital images.

Original language	English (US)
Pages (from-to)	793-802
Number of pages	10
Journal	Journal of Neuropathology and Experimental Neurology
Volume	77
Issue number	9
DOIs	https://doi.org/10.1093/jnen/nly056
State	Published - 2018

Keywords

Biomarker
Biopsy
Colon
Digital imaging
Parkinson disease
Skin
Submandibular gland

ASJC Scopus subject areas

Pathology and Forensic Medicine
Neurology
Clinical Neurology
Cellular and Molecular Neuroscience

Access to Document

10.1093/jnen/nly056

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Beach, T. G., Serrano, G. E., Kremer, T., Canamero, M., Dziadek, S., Sade, H., Derkinderen, P., Corbillé, A. G., Letournel, F., Munoz, D. G., White, C. L., Schneider, J., Crary, J. F., Sue, L. I., Adler, C. H., Glass, M. J., Intorcia, A. J., Walker, J. E., Foroud, T., ... Chahine, L. (2018). Immunohistochemical method and histopathology judging for the systemic synuclein sampling study (S4). Journal of Neuropathology and Experimental Neurology, 77(9), 793-802. https://doi.org/10.1093/jnen/nly056

Immunohistochemical method and histopathology judging for the systemic synuclein sampling study (S4). / Beach, Thomas G.; Serrano, Geidy E.; Kremer, Thomas; Canamero, Marta; Dziadek, Sebastian; Sade, Hadassah; Derkinderen, Pascal; Corbillé, Anne Gaëlle; Letournel, Franck; Munoz, David G.; White, Charles L.; Schneider, Julie; Crary, John F.; Sue, Lucia I.; Adler, Charles H.; Glass, Michael J.; Intorcia, Anthony J.; Walker, Jessica E.; Foroud, Tatiana; Coffey, Christopher S.; Ecklund, Dixie; Riss, Holly; Goßmann, Jennifer; König, Fatima; Kopil, Catherine M.; Arnedo, Vanessa; Riley, Lindsey; Linder, Carly; Dave, Kuldip D.; Jennings, Danna; Seibyl, John; Mollenhauer, Brit; Chahine, Lana.

In: Journal of Neuropathology and Experimental Neurology, Vol. 77, No. 9, 2018, p. 793-802.

Research output: Contribution to journal › Article › peer-review

Beach, TG, Serrano, GE, Kremer, T, Canamero, M, Dziadek, S, Sade, H, Derkinderen, P, Corbillé, AG, Letournel, F, Munoz, DG, White, CL, Schneider, J, Crary, JF, Sue, LI, Adler, CH, Glass, MJ, Intorcia, AJ, Walker, JE, Foroud, T, Coffey, CS, Ecklund, D, Riss, H, Goßmann, J, König, F, Kopil, CM, Arnedo, V, Riley, L, Linder, C, Dave, KD, Jennings, D, Seibyl, J, Mollenhauer, B & Chahine, L 2018, 'Immunohistochemical method and histopathology judging for the systemic synuclein sampling study (S4)', Journal of Neuropathology and Experimental Neurology, vol. 77, no. 9, pp. 793-802. https://doi.org/10.1093/jnen/nly056

Beach, Thomas G. ; Serrano, Geidy E. ; Kremer, Thomas ; Canamero, Marta ; Dziadek, Sebastian ; Sade, Hadassah ; Derkinderen, Pascal ; Corbillé, Anne Gaëlle ; Letournel, Franck ; Munoz, David G. ; White, Charles L. ; Schneider, Julie ; Crary, John F. ; Sue, Lucia I. ; Adler, Charles H. ; Glass, Michael J. ; Intorcia, Anthony J. ; Walker, Jessica E. ; Foroud, Tatiana ; Coffey, Christopher S. ; Ecklund, Dixie ; Riss, Holly ; Goßmann, Jennifer ; König, Fatima ; Kopil, Catherine M. ; Arnedo, Vanessa ; Riley, Lindsey ; Linder, Carly ; Dave, Kuldip D. ; Jennings, Danna ; Seibyl, John ; Mollenhauer, Brit ; Chahine, Lana. / Immunohistochemical method and histopathology judging for the systemic synuclein sampling study (S4). In: Journal of Neuropathology and Experimental Neurology. 2018 ; Vol. 77, No. 9. pp. 793-802.

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title = "Immunohistochemical method and histopathology judging for the systemic synuclein sampling study (S4)",

abstract = "Immunohistochemical (IHC) α-synuclein (Asyn) pathology in peripheral biopsies may be a biomarker of Parkinson disease (PD). The multi-center Systemic Synuclein Sampling Study (S4) is evaluating IHC Asyn pathology within skin, colon and submandibular gland biopsies from 60 PD and 20 control subjects. Asyn pathology is being evaluated by a blinded panel of specially trained neuropathologists. Preliminary work assessed 2 candidate immunoperoxidase methods using a set of PD and control autopsy-derived sections from formalin-fixed, paraffin-embedded blocks of the 3 tissues. Both methods had 100% specificity; one, utilizing the 5C12 monoclonal antibody, was more sensitive in skin (67% vs 33%), and was chosen for further use in S4. Four trainee neuropathologists were trained to perform S4 histopathology readings; in subsequent testing, their scoring was compared to that of the trainer neuropathologist on both glass slides and digital images. Specificity and sensitivity were both close to 100% with all readers in all tissue types on both glass slides and digital images except for skin, where sensitivity averaged 75% with digital images and 83.5% with glass slides. Semiquantitative (0-3) density score agreement between trainees and trainer averaged 67% for glass slides and 62% for digital images.",

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AU - Beach, Thomas G.

AU - Serrano, Geidy E.

AU - Kremer, Thomas

AU - Canamero, Marta

AU - Dziadek, Sebastian

AU - Sade, Hadassah

AU - Derkinderen, Pascal

AU - Corbillé, Anne Gaëlle

AU - Letournel, Franck

AU - Munoz, David G.

AU - White, Charles L.

AU - Schneider, Julie

AU - Crary, John F.

AU - Sue, Lucia I.

AU - Adler, Charles H.

AU - Glass, Michael J.

AU - Intorcia, Anthony J.

AU - Walker, Jessica E.

AU - Foroud, Tatiana

AU - Coffey, Christopher S.

AU - Ecklund, Dixie

AU - Riss, Holly

AU - Goßmann, Jennifer

AU - König, Fatima

AU - Kopil, Catherine M.

AU - Arnedo, Vanessa

AU - Riley, Lindsey

AU - Linder, Carly

AU - Dave, Kuldip D.

AU - Jennings, Danna

AU - Seibyl, John

AU - Mollenhauer, Brit

AU - Chahine, Lana

PY - 2018

Y1 - 2018

N2 - Immunohistochemical (IHC) α-synuclein (Asyn) pathology in peripheral biopsies may be a biomarker of Parkinson disease (PD). The multi-center Systemic Synuclein Sampling Study (S4) is evaluating IHC Asyn pathology within skin, colon and submandibular gland biopsies from 60 PD and 20 control subjects. Asyn pathology is being evaluated by a blinded panel of specially trained neuropathologists. Preliminary work assessed 2 candidate immunoperoxidase methods using a set of PD and control autopsy-derived sections from formalin-fixed, paraffin-embedded blocks of the 3 tissues. Both methods had 100% specificity; one, utilizing the 5C12 monoclonal antibody, was more sensitive in skin (67% vs 33%), and was chosen for further use in S4. Four trainee neuropathologists were trained to perform S4 histopathology readings; in subsequent testing, their scoring was compared to that of the trainer neuropathologist on both glass slides and digital images. Specificity and sensitivity were both close to 100% with all readers in all tissue types on both glass slides and digital images except for skin, where sensitivity averaged 75% with digital images and 83.5% with glass slides. Semiquantitative (0-3) density score agreement between trainees and trainer averaged 67% for glass slides and 62% for digital images.

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KW - Biopsy

KW - Colon

KW - Digital imaging

KW - Parkinson disease

KW - Skin

KW - Submandibular gland

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