Expression of Syk and MAP4 proteins in ovarian cancer.

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.