Abstract
Dysregulation of lipid metabolism is common in cancer. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) has been implicated with various cancer types. Here we analyzed by immunohistochemistry its expression in 2,197 breast cancers. LPCAT1 staining was found in 97.8% of 1,774 interpretable tumors, including 48.1% with weak, 28.7% with moderate, and 14.4% with strong expression. The frequency of LPCAT1 positivity depended on the histological tumor type. Moderate or strong LPCAT1 positivity was more common in cancers of no special type (NST) (46.2%) than in lobular carcinomas (25.9%; p<0.0001). Strong LPCAT1 was associated with BRE grade, tumor cell proliferation and overall survival in all cancers and in the subgroup of NST cancers (p<0.0001, each). In the subset of NST cancers the prognostic effect of LPCAT1 expression was independent of pT, and BRE grade (p<0.0001 each). A comparison with molecular features showed that LPCAT1 was strongly associated with estrogen receptor negativity (p<0.0001), progesterone receptor negativity (p<0,0001), amplification of HER2 (p<0.0001) and MYC (p=0.0066), as well as deletions of PTEN (p<0.0001) and CDKNA2 (p=0.0151). It is concluded that LPCAT1 overexpression is linked to adverse tumor features and poor prognosis in breast cancer. These data also highlight the important role of lipid metabolism in breast cancer biology.
Highlights
Breast cancer is the most common cancer in females worldwide and is the leading cause of cancerrelated deaths in the female population [1]
Normal breast tissues showed moderate to strong Lysophosphatidylcholine acyltransferase 1 (LPCAT1) expression in luminal cells under the selected experimental conditions
LPCAT1 expression varied between histological breast cancer subtypes (Table 1)
Summary
Breast cancer is the most common cancer in females worldwide and is the leading cause of cancerrelated deaths in the female population [1]. Surgical removal of the cancer is the standard therapy. Whether adjuvant systemic treatment is performed or not depends on the individual risk situation. The histological grade, tumor size and presence of lymph node metastasis are basic parameters to assess the prognosis of individual patients. Additional molecular analyses are increasingly employed but still not sufficient to reliably determine tumor aggressiveness [2, 3]. The analysis of further molecular properties could eventually improve the reliability of prediction of tumor aggressiveness
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