Role of bruton’s tyrosine kinase in stage III colorectal cancer

Debora Basile, Lorenzo Gerratana, Angela Buonadonna, Silvio Ken Garattini, Tiziana Perin, Emanuela Grassilli, Gianmaria Miolo, Maria Grazia Cerrito, Claudio Belluco, Giulio Bertola, Antonino De Paoli, Renato Cannizzaro, Marialuisa Lavitrano, Fabio Puglisi, Vincenzo Canzonieri

Research output: Contribution to journalArticle

Abstract

Background: Bruton’s tyrosine kinase (BTK) is involved in the immune response and its deficiency impairs B cell maturation. We evaluated the expression of a novel BTK isoform, p65BTK, in colorectal cancer (CRC), to identify its impact on survival. Materials and Methods: This retrospective study evaluated 87 consecutive stage III CRC patients treated at the National Cancer Institute of Aviano (1999-2017). Multiple specimens were collected and analyzed for staining intensity and percentage of tumor cells positive for p65BTK. Prognostic impact was tested by univariate Cox regression analysis. Results: After a median follow-up of 82.59 months, median disease-free survival (DFS) and overall survival (OS) were 11.67 months and 31.33 months, respectively. Interestingly, 10% of patients did not express p65BTK. For the immunohistochemistry IHC intensity 1, the best cutoff point was 1% of p65BTK positivity; for IHC intensity 2, it was 50%; and for IHC intensity 3, it was 80%. Through univariate analysis, patients with highly expressed p65BTK (IHC intensity 3 and ≥80%) were shown to have the worst prognosis in terms of DFS (HR: 6.23; p = 0.005; 95% C.I. 1.75-22.79) and OS (HR: 2.54; p = 0.025; 95% C.I. 1.12-5.76). Conclusions: p65BTK is frequently expressed in CRC and, if highly expressed, is an unfavourable prognostic factor. However, further confirmation is needed and its potential targeting needs to be studied.

Original languageEnglish
Article number880
Number of pages13
JournalCancers
Volume11
Issue number6
DOIs
Publication statusPublished - Jun 2019

Keywords

  • Bruton’s tyrosine kinase
  • BTK
  • Colon cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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