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J Cancer Res Clin Oncol. 2019 Feb 8. doi: 10.1007/s00432-019-02856-9. [Epub ahead of print]

Expression of Syk and MAP4 proteins in ovarian cancer.

Author information

1
Academic Clinical Oncology, Nottingham Breast Cancer Research Centre, School of Medicine, University of Nottingham, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, NG5 1PB, UK.
2
Department of Pathology, Queen's Medical Centre, Nottingham University Hospital, Nottingham, NG7 2UH, UK.
3
Academic Clinical Oncology, Nottingham Breast Cancer Research Centre, School of Medicine, University of Nottingham, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, NG5 1PB, UK. stewart.martin@nottingham.ac.uk.

Abstract

PURPOSE:

We have previously reported on the prognostic importance of the calpain family of proteins in ovarian cancer, especially calpain-2. Spleen tyrosine kinase (Syk) phosphorylates a variety of cytoskeletal proteins with studies suggesting potential interactions between Syk and conventional calpains. Microtubule-associated protein 4 (MAP4) has been reported to be regulated by Syk.

METHODS:

The current study assessed Syk and MAP4 protein expression, by immunohistochemistry on a tissue microarray comprised of cores from primary ovarian carcinomas (n = 575), to evaluate associations with patient clinical outcomes and other clinicopathological factors and sought to determine whether there were any correlations between the expression of Syk, MAP4 and the calpain system.

RESULTS:

MAP4 expression was significantly associated with ovarian cancer histological subtype (P < 0.001), stage (P = 0.001), grade (P < 0.001) and residual tumour (P = 0.005). Despite this finding, we found no significant association existing between MAP4 expression and overall survival. Syk expression was also found significantly associated with histological subtype (P < 0.001). Syk seems to play a contradictory role with respect to tumour progression: low cytoplasmic Syk expression was significantly associated with low stage (P = 0.013), and low nuclear Syk expression with chemo-resistance in patients treated with taxane-containing therapy (P = 0.006). Interestingly, despite the lack of association in the whole cohort, high nuclear Syk expression was significantly associated with better overall survival in certain subgroups (P = 0.001).

CONCLUSIONS:

The current study indicates a lack of correlation between calpain-2 expression and Syk and MAP4. Syk, MAP4 and calpain-1 appeared to significantly correlate with each other in the whole cohort, with calpain-1 being more highly associated with MAP4 and Syk in mucinous carcinomas. Overall, the current results suggest that Syk, MAP4, and calpain-1 expression are correlated with each other and these proteins may be involved in early stages of tumour spread.

KEYWORDS:

Calpain; Calpastatin; Chemotherapy; MAP4; Ovarian cancer; Syk

PMID:
30737623
DOI:
10.1007/s00432-019-02856-9

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