The important role of routine cytopathology in pediatric precision oncology.

cytopathology pediatrics precision oncology primary cell culture validation study

Journal

Cancer cytopathology
ISSN: 1934-6638
Titre abrégé: Cancer Cytopathol
Pays: United States
ID NLM: 101499453

Informations de publication

Date de publication:
10 2021
Historique:
revised: 14 04 2021
received: 15 03 2021
accepted: 16 04 2021
pubmed: 28 5 2021
medline: 12 2 2022
entrez: 27 5 2021
Statut: ppublish

Résumé

The development of high-throughput drug screening (HTS) using primary cultures provides a promising, clinically translatable approach to tailoring treatment strategies for patients with cancer. However, this has been challenging for solid tumors because of often limited amounts of tissue available. In most cases, in vitro expansion is required before HTS, which may lead to overgrowth and contamination by non-neoplastic cells. In this study, hematoxylin and eosin staining and immunohistochemical staining were performed on 129 cytopathology cases from 95 patients. These cytopathology cases comprised cell block preparations derived from primary tumor specimens or patient-derived xenografts as part of a pediatric precision oncology trial. Cytopathology cases were compared with the morphology and immunohistochemical staining profile of the original tumor. Cases were reported as tumor cells present, equivocal, or tumor cells absent. The HTS results from cytopathologically validated cultures were incorporated into a multidisciplinary tumor board report issued to the treating clinician to guide clinical decision making. On cytopathologic examination, tumor cells were present in 77 of 129 cases (60%) and were absent in 38 of 129 cases (29%), whereas 14 of 129 cases (11%) were equivocal. Cultures that contained tumor cells resembled the tumors from which they were derived. Cytopathologic examination of tumor cell block preparations is feasible and provides detailed morphologic characterization. Cytopathologic examination is essential for ensuring that samples submitted for HTS contain representative tumor cells and that in vitro drug sensitivity data are clinically translatable.

Sections du résumé

BACKGROUND
The development of high-throughput drug screening (HTS) using primary cultures provides a promising, clinically translatable approach to tailoring treatment strategies for patients with cancer. However, this has been challenging for solid tumors because of often limited amounts of tissue available. In most cases, in vitro expansion is required before HTS, which may lead to overgrowth and contamination by non-neoplastic cells.
METHODS
In this study, hematoxylin and eosin staining and immunohistochemical staining were performed on 129 cytopathology cases from 95 patients. These cytopathology cases comprised cell block preparations derived from primary tumor specimens or patient-derived xenografts as part of a pediatric precision oncology trial. Cytopathology cases were compared with the morphology and immunohistochemical staining profile of the original tumor. Cases were reported as tumor cells present, equivocal, or tumor cells absent. The HTS results from cytopathologically validated cultures were incorporated into a multidisciplinary tumor board report issued to the treating clinician to guide clinical decision making.
RESULTS
On cytopathologic examination, tumor cells were present in 77 of 129 cases (60%) and were absent in 38 of 129 cases (29%), whereas 14 of 129 cases (11%) were equivocal. Cultures that contained tumor cells resembled the tumors from which they were derived.
CONCLUSIONS
Cytopathologic examination of tumor cell block preparations is feasible and provides detailed morphologic characterization. Cytopathologic examination is essential for ensuring that samples submitted for HTS contain representative tumor cells and that in vitro drug sensitivity data are clinically translatable.

Identifiants

pubmed: 34043284
doi: 10.1002/cncy.22448
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

805-818

Subventions

Organisme : Cure Brain Cancer Foundation
Organisme : Cancer Therapeutics Cooperative Research Centre
Organisme : Robert Connor Dawes Foundation
Organisme : National Health and Medical Research Council of Australia
ID : APP1059804
Organisme : National Health and Medical Research Council of Australia
ID : APP1157871
Organisme : Australian Federal Government Department of Health funding

Informations de copyright

© 2021 American Cancer Society.

Références

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Auteurs

Jinhan Xie (J)

Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales (UNSW) Sydney, Randwick, New South Wales, Australia.
School of Women's and Children's Health, UNSW Sydney, Randwick, New South Wales, Australia.

Amit Kumar (A)

Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales (UNSW) Sydney, Randwick, New South Wales, Australia.
Peter MacCallum Cancer Center, Melbourne, Victoria, Australia.

M Emmy M Dolman (MEM)

Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales (UNSW) Sydney, Randwick, New South Wales, Australia.

Chelsea Mayoh (C)

Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales (UNSW) Sydney, Randwick, New South Wales, Australia.
School of Women's and Children's Health, UNSW Sydney, Randwick, New South Wales, Australia.

Dong-Anh Khuong-Quang (DA)

Children's Cancer Center, Murdoch Children's Research Institute, The Royal Children's Hospital, Melbourne, Victoria, Australia.

Roxanne Cadiz (R)

Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales (UNSW) Sydney, Randwick, New South Wales, Australia.

Marie Wong-Erasmus (M)

Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales (UNSW) Sydney, Randwick, New South Wales, Australia.

Emily V A Mould (EVA)

Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales (UNSW) Sydney, Randwick, New South Wales, Australia.

Dylan Grebert-Wade (D)

Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales (UNSW) Sydney, Randwick, New South Wales, Australia.

Paulette Barahona (P)

Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales (UNSW) Sydney, Randwick, New South Wales, Australia.

Alvin Kamili (A)

Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales (UNSW) Sydney, Randwick, New South Wales, Australia.
School of Women's and Children's Health, UNSW Sydney, Randwick, New South Wales, Australia.

Maria Tsoli (M)

Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales (UNSW) Sydney, Randwick, New South Wales, Australia.

Timothy W Failes (TW)

Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales (UNSW) Sydney, Randwick, New South Wales, Australia.
Australian Cancer Research Foundation Drug Discovery Center, Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Randwick, New South Wales, Australia.

Shu-Oi Chow (SO)

Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales (UNSW) Sydney, Randwick, New South Wales, Australia.
Australian Cancer Research Foundation Drug Discovery Center, Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Randwick, New South Wales, Australia.

Greg M Arndt (GM)

Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales (UNSW) Sydney, Randwick, New South Wales, Australia.
Australian Cancer Research Foundation Drug Discovery Center, Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Randwick, New South Wales, Australia.

Kanika Bhatia (K)

Children's Cancer Center, Murdoch Children's Research Institute, The Royal Children's Hospital, Melbourne, Victoria, Australia.

Glenn M Marshall (GM)

Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales (UNSW) Sydney, Randwick, New South Wales, Australia.
Kids Cancer Center, Sydney Children's Hospital, Randwick, New South Wales, Australia.

David S Ziegler (DS)

Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales (UNSW) Sydney, Randwick, New South Wales, Australia.
School of Women's and Children's Health, UNSW Sydney, Randwick, New South Wales, Australia.
Kids Cancer Center, Sydney Children's Hospital, Randwick, New South Wales, Australia.

Michelle Haber (M)

Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales (UNSW) Sydney, Randwick, New South Wales, Australia.
School of Women's and Children's Health, UNSW Sydney, Randwick, New South Wales, Australia.

Richard B Lock (RB)

Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales (UNSW) Sydney, Randwick, New South Wales, Australia.
School of Women's and Children's Health, UNSW Sydney, Randwick, New South Wales, Australia.

Vanessa Tyrrell (V)

Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales (UNSW) Sydney, Randwick, New South Wales, Australia.

Loretta Lau (L)

Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales (UNSW) Sydney, Randwick, New South Wales, Australia.
Children's Cancer Center, Royal Children's Hospital, Parkville, Victoria, Australia.

Penny Athanasatos (P)

Department of Anatomical Pathology, Prince of Wales Hospital, Randwick, New South Wales, Australia.

Andrew J Gifford (AJ)

Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales (UNSW) Sydney, Randwick, New South Wales, Australia.
School of Women's and Children's Health, UNSW Sydney, Randwick, New South Wales, Australia.
Department of Anatomical Pathology, Prince of Wales Hospital, Randwick, New South Wales, Australia.

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