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Immunohistochemistry subtyping of urothelial carcinoma is feasible in the daily practice

Queipo, Francisco Javier ; Unamunzaga, Gorka Muñiz ; Negro, Begoña Fuertes ; Fuertes, Sandra Gracia ; Cortés, Marina Álvarez ; Tejedor, Elena Carceller ; Mañas, Carmen María Bernal ; Ariño, Arceli Bono ; Sjödahl, Gottfrid LU and Beorlegui, Carmen (2022) In Virchows Archiv 481(2). p.191-200
Abstract

The preferred treatment of choice in muscle-invasive bladder cancer (MIBC) is usually transurethral resection followed by cystectomy, with neoadjuvant chemotherapy being a second option. As the treatment is associated with relevant side effects, a great effort is being made to improve the selection of patients, with molecular subtyping being one of the main strategies. Our aim was to develop an immunohistochemical algorithm for subtyping MIBCs. After a literature review, we have developed a simple algorithm to subtype MIBCs based on their morphology and three common antibodies: GATA3, CK5/6, and p16. We applied it to 113 muscle-invasive carcinomas. The positivity threshold for GATA3 and CK5/6 was 20% with at least moderate intensity,... (More)

The preferred treatment of choice in muscle-invasive bladder cancer (MIBC) is usually transurethral resection followed by cystectomy, with neoadjuvant chemotherapy being a second option. As the treatment is associated with relevant side effects, a great effort is being made to improve the selection of patients, with molecular subtyping being one of the main strategies. Our aim was to develop an immunohistochemical algorithm for subtyping MIBCs. After a literature review, we have developed a simple algorithm to subtype MIBCs based on their morphology and three common antibodies: GATA3, CK5/6, and p16. We applied it to 113 muscle-invasive carcinomas. The positivity threshold for GATA3 and CK5/6 was 20% with at least moderate intensity, while p16 was 70% with moderate to intense nuclear and cytoplasmic staining. Cases GATA3 + CK5/6 − were considered luminal, while cases GATA3 − CK5/6 + were classified as nonluminal/basal squamous. Luminal p16 + cases were labeled as genomically unstable and luminal p16 − as Uro-like. Cases GATA3 + CK5/6 + with a predominantly basal pattern were labeled luminal, while diffuse cases were labeled nonluminal/basal squamous. All GATA3-CK5/6 − cases were considered nonluminal and were divided into mesenchymal-like or neuroendocrine, depending on the morphology. We were able to classify the 113 cases as: 82 (72.57%) were luminal, being 47 Uro-like (41.59%) and 35 (30.97%) genomically unstable; 31 (27.43%) were nonluminal, being 24 basal/squamous (21.24%), two (1.76%) mesenchymal-like, and five (4.42%) neuroendocrine like. We have achieved a feasible and cost-effective algorithm to subtype MIBCs from morphological features and the use of three common antibodies. Further studies in external cohorts are necessary to validate these results.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Bladder carcinoma, CK 5/6, GATA3, Immunohistochemistry, Staining, Subtyping
in
Virchows Archiv
volume
481
issue
2
pages
191 - 200
publisher
Springer
external identifiers
  • pmid:35731280
  • scopus:85132380896
ISSN
0945-6317
DOI
10.1007/s00428-022-03361-0
language
English
LU publication?
yes
id
677b400d-f55e-443a-ac56-9ac30794de65
date added to LUP
2022-09-29 09:27:13
date last changed
2024-04-18 14:32:54
@article{677b400d-f55e-443a-ac56-9ac30794de65,
  abstract     = {{<p>The preferred treatment of choice in muscle-invasive bladder cancer (MIBC) is usually transurethral resection followed by cystectomy, with neoadjuvant chemotherapy being a second option. As the treatment is associated with relevant side effects, a great effort is being made to improve the selection of patients, with molecular subtyping being one of the main strategies. Our aim was to develop an immunohistochemical algorithm for subtyping MIBCs. After a literature review, we have developed a simple algorithm to subtype MIBCs based on their morphology and three common antibodies: GATA3, CK5/6, and p16. We applied it to 113 muscle-invasive carcinomas. The positivity threshold for GATA3 and CK5/6 was 20% with at least moderate intensity, while p16 was 70% with moderate to intense nuclear and cytoplasmic staining. Cases GATA3 + CK5/6 − were considered luminal, while cases GATA3 − CK5/6 + were classified as nonluminal/basal squamous. Luminal p16 + cases were labeled as genomically unstable and luminal p16 − as Uro-like. Cases GATA3 + CK5/6 + with a predominantly basal pattern were labeled luminal, while diffuse cases were labeled nonluminal/basal squamous. All GATA3-CK5/6 − cases were considered nonluminal and were divided into mesenchymal-like or neuroendocrine, depending on the morphology. We were able to classify the 113 cases as: 82 (72.57%) were luminal, being 47 Uro-like (41.59%) and 35 (30.97%) genomically unstable; 31 (27.43%) were nonluminal, being 24 basal/squamous (21.24%), two (1.76%) mesenchymal-like, and five (4.42%) neuroendocrine like. We have achieved a feasible and cost-effective algorithm to subtype MIBCs from morphological features and the use of three common antibodies. Further studies in external cohorts are necessary to validate these results.</p>}},
  author       = {{Queipo, Francisco Javier and Unamunzaga, Gorka Muñiz and Negro, Begoña Fuertes and Fuertes, Sandra Gracia and Cortés, Marina Álvarez and Tejedor, Elena Carceller and Mañas, Carmen María Bernal and Ariño, Arceli Bono and Sjödahl, Gottfrid and Beorlegui, Carmen}},
  issn         = {{0945-6317}},
  keywords     = {{Bladder carcinoma; CK 5/6; GATA3; Immunohistochemistry; Staining; Subtyping}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{191--200}},
  publisher    = {{Springer}},
  series       = {{Virchows Archiv}},
  title        = {{Immunohistochemistry subtyping of urothelial carcinoma is feasible in the daily practice}},
  url          = {{http://dx.doi.org/10.1007/s00428-022-03361-0}},
  doi          = {{10.1007/s00428-022-03361-0}},
  volume       = {{481}},
  year         = {{2022}},
}