Intracellular signalling pathways play a role for treatment response and outcome for patients with breast cancer (BC).
We analysed phosphorylated MAPK (pJNK, pERK, pp38) and pAkt with a commercial multiplex enzyme-linked immunosorbent assay (ELISA) (Luminex®) and M30, a marker of apoptosis, in 449 patients with primary ER-positive BC. The aim was to determine the relation between pMAPK, proliferation, apoptosis, and survival in Invasie Lobular Carcinoma (ILC) and non-Invasive Lobular Carcinoma (non-ILC).
Medium follow up was 18.9 years and ILC and non-ILC had an equal Relapse Free Survival (RFS) (p=0.68). In the whole population pAkt was the only kinase with prognostic information; patients with absent/low levels of pAkt had a worse RFS (p=0.016). A multivariate analysis showed tumour size (HR=1.8) (p=0.0016), nodal status (HR=2.8) (p<0.001) and absent/low pAkt (HR=0.69) (p=0.059) as independent prognostic factors. There was a difference between ILC and non-ILC concerning expression of estrogen receptor (ER) (p=0.033), apoptosis (p<0.001), pERK (p=0.004), pJNK (p<0.001) and pp38 (p=0.005) whilst nodal status, Progesteron Receptor (PGR), proliferation rate and pAKT were equal. ILC had a trend towards larger size, but this did not reach statistical significance (p=0.059). Proliferation was correlated to RFS in non-ILC (p<0.001) but not in ILC (p=0.94). pMAPK were not correlated to RFS when patients were split in ILC and non-ILC.
We show differences in expression of activated MAPKs in ILC and non-ILC. Despite lower proliferation and apoptosis, we could not show any correlation to survival in ILC, but this may indicate a more stem cells like behaviour. ER-positive ILC and non-ILC have similar survival, pAkt was the only kinase with prognostic information.
The authors.
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All authors have declared no conflicts of interest.