TY - JOUR
T1 - Role of bruton’s tyrosine kinase in stage III colorectal cancer
AU - Basile, Debora
AU - Gerratana, Lorenzo
AU - Buonadonna, Angela
AU - Garattini, Silvio Ken
AU - Perin, Tiziana
AU - Grassilli, Emanuela
AU - Miolo, Gianmaria
AU - Cerrito, Maria Grazia
AU - Belluco, Claudio
AU - Bertola, Giulio
AU - De Paoli, Antonino
AU - Cannizzaro, Renato
AU - Lavitrano, Marialuisa
AU - Puglisi, Fabio
AU - Canzonieri, Vincenzo
PY - 2019/6
Y1 - 2019/6
N2 - 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.
AB - 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.
KW - Bruton’s tyrosine kinase
KW - BTK
KW - Colon cancer
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U2 - 10.3390/cancers11060880
DO - 10.3390/cancers11060880
M3 - Article
AN - SCOPUS:85069750081
VL - 11
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 6
M1 - 880
ER -