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Low Frequency of Intratumor Heterogeneity in Bladder Cancer Tissue Microarrays

Jakobsson, Lovisa LU ; Chebil, Gunilla; Marzouka, Nour Al Dain LU ; Liedberg, Fredrik LU and Sjödahl, Gottfrid LU (2018) In Bladder Cancer 4(3). p.327-337
Abstract

Background: Intratumoral heterogeneity (ITH) is associated with clinical challenges such as possible differences in response to treatment and difficulties in classifying the tumor. Previously, ITH has been described in bladder cancer using detailed genetic analyses. However, in this disease, it is not known to what extent ITH actually occurs, or if it involves molecular subtyping, when assessment is achieved by immunohistochemistry (IHC) on the protein level using tissue microarrays (TMAs), the method most widely applied when analyzing large sample numbers. Objective: We aimed to investigate ITH by IHC in bladder cancer TMAs. Methods: Staining for eleven immunohistochemical markers (CK5, Cyclin D1, E-Cadherin, EGFR, FGFR, GATA3, HER2,... (More)

Background: Intratumoral heterogeneity (ITH) is associated with clinical challenges such as possible differences in response to treatment and difficulties in classifying the tumor. Previously, ITH has been described in bladder cancer using detailed genetic analyses. However, in this disease, it is not known to what extent ITH actually occurs, or if it involves molecular subtyping, when assessment is achieved by immunohistochemistry (IHC) on the protein level using tissue microarrays (TMAs), the method most widely applied when analyzing large sample numbers. Objective: We aimed to investigate ITH by IHC in bladder cancer TMAs. Methods: Staining for eleven immunohistochemical markers (CK5, Cyclin D1, E-Cadherin, EGFR, FGFR, GATA3, HER2, p16, p63, P-Cadherin and RB1)was performed, and differences in staining patterns were assessed both within 1981 individual tissue-cores and by comparing two cores from the same tumor in 948 cases according to our pre-specified criteria. Presence of ITH was associated with clinicopathological data such as stage, grade, molecular subtype and survival. Results: Intracore ITH in one or several markerswas associated with grade 3, stage T1 and the genomically unstable molecular subtype. ITH in three or more markers was found in 5% between cores (intercore heterogeneity) and in 2% within cores (intracore heterogeneity). No association with survival was found for any of the ITH groups. Conclusions: We observed ITH in a small proportion of the tumors, suggesting that ITH has only a limited impact on TMA bladder cancer studies.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Bladder cancer, immunohistochemistry, intratumoral heterogeneity
in
Bladder Cancer
volume
4
issue
3
pages
11 pages
publisher
IOS Press
external identifiers
  • scopus:85051993822
ISSN
2352-3727
DOI
10.3233/BLC-180176
language
English
LU publication?
yes
id
ad230e2e-85cc-4dca-ae96-aad415bc0742
date added to LUP
2018-09-27 14:47:58
date last changed
2019-02-20 11:28:08
@article{ad230e2e-85cc-4dca-ae96-aad415bc0742,
  abstract     = {<p>Background: Intratumoral heterogeneity (ITH) is associated with clinical challenges such as possible differences in response to treatment and difficulties in classifying the tumor. Previously, ITH has been described in bladder cancer using detailed genetic analyses. However, in this disease, it is not known to what extent ITH actually occurs, or if it involves molecular subtyping, when assessment is achieved by immunohistochemistry (IHC) on the protein level using tissue microarrays (TMAs), the method most widely applied when analyzing large sample numbers. Objective: We aimed to investigate ITH by IHC in bladder cancer TMAs. Methods: Staining for eleven immunohistochemical markers (CK5, Cyclin D1, E-Cadherin, EGFR, FGFR, GATA3, HER2, p16, p63, P-Cadherin and RB1)was performed, and differences in staining patterns were assessed both within 1981 individual tissue-cores and by comparing two cores from the same tumor in 948 cases according to our pre-specified criteria. Presence of ITH was associated with clinicopathological data such as stage, grade, molecular subtype and survival. Results: Intracore ITH in one or several markerswas associated with grade 3, stage T1 and the genomically unstable molecular subtype. ITH in three or more markers was found in 5% between cores (intercore heterogeneity) and in 2% within cores (intracore heterogeneity). No association with survival was found for any of the ITH groups. Conclusions: We observed ITH in a small proportion of the tumors, suggesting that ITH has only a limited impact on TMA bladder cancer studies.</p>},
  author       = {Jakobsson, Lovisa and Chebil, Gunilla and Marzouka, Nour Al Dain and Liedberg, Fredrik and Sjödahl, Gottfrid},
  issn         = {2352-3727},
  keyword      = {Bladder cancer,immunohistochemistry,intratumoral heterogeneity},
  language     = {eng},
  month        = {07},
  number       = {3},
  pages        = {327--337},
  publisher    = {IOS Press},
  series       = {Bladder Cancer},
  title        = {Low Frequency of Intratumor Heterogeneity in Bladder Cancer Tissue Microarrays},
  url          = {http://dx.doi.org/10.3233/BLC-180176},
  volume       = {4},
  year         = {2018},
}