Elevated Heat Shock Protein Linked to Cancer Prognosis

Patients whose estrogen receptor (ER)-positive breast cancers have high levels of the heat shock factor 1 (HSF1) experience poor outcomes including increased mortality.

Patient prognoses can vary widely although ER-positive breast cancers are often associated with better outcomes than other breast cancer-tumor types, including those that are negative for the Human Epidermal growth factor Receptor (HER-2) receptor and so-called triple negative breast cancers.

Scientists at the Whitehead Institute of Biomedical Research (Cambridge, MA, USA) collaborating with others, examined HSF1 levels in breast cancer tissue samples from 1,841 participants in one of the largest and longest-running epidemiological studies of women's health. They looked at the relationship between HSF1 status, using tissue microarrays and immunohistochemical staining of paraffin blocks, and the participants' outcomes.

Compared with ER-positive breast cancer patients with low levels of HSF1, those with high levels of HSF1 had a poorer outcome, including increased mortality. The investigators also noted that invasive ER-positive tumors with elevated HSF1 levels tended to be larger and more aggressive than those with normal HSF1 levels did. The heat shock response, which is controlled by transcription factors like HSF1, enables cells to withstand temperature spikes and other stressors. Cancer cells are deviants that live in a tumor's milieu, which lacks abundant nutrients and oxygen, but is crammed with distorted and abnormal proteins. To survive these exceptionally stressful circumstances, many cancer cells have usurped the normally beneficial heat shock response to support their existence.

Because of this strong link between HSF1 concentrations and prognosis, HSF1 testing could become a valuable part of the oncologist's toolkit. Sandro Santagata, MD, PhD, lead author and an instructor in pathology at Brigham and Women's Hospital (Boston, MA, USA) said, "If HSF1 status can help predict which of the ER-positive patients will do well with standard treatments and which ones won't, that would be really helpful. In terms of understanding the biology, we think these findings are really important for reinforcing our interest in pursuing the heat shock response itself as a therapeutic target." The study was published October 31, 2011 in the Proceedings of the National Academy of Sciences of the United States (PNAS).

Related Links:
Whitehead Institute of Biomedical Research
Brigham and Women's Hospital