[224] The Relation between Melatonin MT1 Receptor and Oncotype Recurrence Score in HER 2- Positive and Negative Breast Cancers

Gabriela M Oprea-Ilies, Erhard Haus, Lauren A McLendon, Linda L Sackett-Lundeen, Robert Busch, Amy Adams, Cynthia Cohen. Emory University, Atlanta, GA; University of Minnesota, Minneapolis, MN; Health Partners, St. Paul, MN

Background: Melatonin, the main secretory product of the pineal gland regulates cell proliferation via the melatonin receptor MT1 (MT1R). Anti-proliferative actions of melatonin on human and animal cell lines have been reported in breast cancer (BC). These oncostatic actions of melatonin are enhanced by MT1R overexpression and by melatonin receptor agonists, and they are inhibited by luzindole, an MT1 inhibitor.
At physiologic concentrations, melatonin suppresses the growth of human BC cell lines that are estrogen receptor alpha (ERα) positive and some that are ERα negative in vitro and in in xenograft models. Most BC express MT1R. The relationship between MT1 expression and genetic factors determining the behavior of breast cancer is unknown. In tumor cells, melatonin interacts with hormonal and other factors, including the epidermal growth factors. We aim to investigate the presence of melatonin MT1 receptors in relation to breast cancer markers (ER, PR, HER2/neu) and to the Oncotype recurrence score (ORS).
Design: 130 invasive mammary carcinomas (IMC) were included. Tissue microarrays constructed with two 1 mm cores from each BC were stained with a polyclonal antibody to MT1 (Chemica International 1/40). The product of staining intensity (1-3) and % of positive cells gave the numerical score (NS). BC markers: ER, PR and Her2/neu (HER) were studied by immunohistochemistry (IHC) with HER confirmed by FISH when equivocal. ORS on ER-positive, lymph node-negative BC was performed by Genomic Health, Redwood City California.
Results: 130 BC were studied. The correlation of NS of MT1R correlates negatively with the ORS (Table 1).

MT1R and Oncogene Recurrence Score
dfF-Testp ValueNoRY InterceptSlope
14.0890.0453126- 0.1786721.541- 0.019


Higher ORS, with worse prognosis and tendency for progression, is associated with lower MT1 receptor expression.
The MT1 receptor score is not statistically different between HER2 positive and negative, hormone positive and negative BC. (Table 2)

MT1 Receptor and BC Phenotype:
PhenotypeNumber Positive/Negative% Positive
HER213/7515
ER58/3066
PR47/4153
ANOVA: NS


Conclusions: 1. In animal studies the MT1R relates to tumor inhibition and better prognosis. In our study, in human breast carcinomas the higher the Oncotype recurrence score, indicating unfavorable course, the lower MT1R.
2. A possible relation of genetic determinants of tumor behavior with MT1R expression is of interest in breast oncogenesis.
Category: Breast

Wednesday, March 21, 2012 1:00 PM

Poster Session VI # 19, Wednesday Afternoon

 

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