Quinlan, P. R., Sreseli, R., Quinlan, R. A.
, Hadad, S., Bray, S. E., Kernohan, N., Kellock, D., Baker, L., Purdie, C., Jordan, L. & Thompson, A. M. (2009). alpha B-crystallin, vimentin and increased p53 expression levels in breast cancer is associated with poor prognosis. Cancer Research 69
(2 Suppl): 321S-322S.
Author(s) from Durham
ackground: Previous studies have identified αB-crystallin as a marker of poor prognosis for breast cancer and have suggested that it is an excellent marker for tumours of basal origin. Increased expression of αB-crystallin has been associated with anchorage-independent growth and metastasis leading to the suggestion that αB-crystallin is an oncoprotein. We have considered whether the αB-crystallin binding proteins, vimentin and HSP27 also show a similar association with poor prognosis. We also investigated whether either HSP27 phosphorylation HSP27 or p53 expression could be associated with αB-crystallin expression.
Methods: Tissue Micro Arrays of 0.6x0.6mm cores of 205 breast cancers were stained with antibodies to αB-crystallin, vimentin, p53 (antibodies DO1, FP3), HSP27 (antibody ERD5) and HSP27 82P. The levels of protein expressions were then compared with clinical and pathological parameters.
Results: The expression of αB-crystallin was positively associated with vimentin (P<0.001 Fisher's exact test (FET)). We have confirmed that αB-crystallin expression is linked to a low expression of the estrogen receptor and reduced survival (P<0.001 (FET), P=0.002 Kaplan Meier Log Rank (KM) respectively). Vimentin expression was similarly associated with estrogen receptor (ER) negative cancers and poor survival (P <0.001 (FET), P= 0.002 (KM Log Rank) respectively). Low expression of HSP27 resulted in poor three-year survival (P=0.007 (KM Log Rank)), but longer-term survival was unaffected (P=0.09 (KM Log Rank)). In contrast to αB-crystallin, low expression of HSP27 was associated with ER and progesterone receptor (PGR) negativity (P<0.001 (FET), P=0.001 (FET)). HSP27 82P similarly resulted in poor three-year survival (P=0.01 (KM Log Rank)) compared with longer-term survival (P=0.05 (KM Log Rank)). In samples positive for either αB-crystallin or vimentin, a strong association with increased p53 expression (p53 antibodies: DO1(P<0.001 (FET)) and FP3(P<0.001 (FET))) was found.
Conclusions: The increased expression of the protein chaperone, αB-crystallin was linked with reduced survival as well as it's binding partner, vimentin. We found that within this patient subgroup, there was an increased level of p53. The potential functional significance of this interaction for metastasis will be discussed in the context of other predictive markers for breast cancer. A similar association was not found for HSP27 expression.