Low Frequency of Intratumor Heterogeneity in Bladder Cancer Tissue Microarrays

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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, 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.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Lund University
  • Skåne University Hospital
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cancer och onkologi

Nyckelord

Originalspråkengelska
Sidor (från-till)327-337
Antal sidor11
TidskriftBladder Cancer
Volym4
Utgåva nummer3
StatusPublished - 2018 jul 30
PublikationskategoriForskning
Peer review utfördJa