Distribution of GPR30, a seven membrane-spanning estrogen receptor, in primary breast cancer and its association with clinicopathologic determinants of tumor progression.
OBJECTIVE
The seven transmembrane receptor, GPR30, is linked to estrogen binding and heparan-bound epidermal growth factor release. Here, the significance of GPR30 in human breast cancer was evaluated by comparing its relationship to steroid hormone receptor expression and tumor progression variables.


METHODS
Immunohistochemical analysis of a National Cancer Institute-sponsored tumor collection comprised of 361 breast carcinomas obtained at first diagnosis (321 invasive and 40 intraductal tumors). Biopsies from 12 reduction mammoplasties served as controls. The distribution pattern of GPR30, estrogen receptor (ER), and progesterone receptor (PR) was correlated with clinicopathologic variables obtained at diagnosis.


RESULTS
GPR30, ER, and PR were positive in all 12 normal controls. In contrast, GPR30 expression varied in breast tumors, in which 62% (199 of 321) of invasive tumors and 42% (17 of 40) of intraductal tumors were positive. Codistribution of ER and GPR30 was measured in 43% (139 of 321) of invasive breast tumors, whereas both receptors were lacking (ER-GPR30-) in 19% (61 of 321) of the tumors analyzed, indicating a significant association between ER and GPR30 (P<0.05). The coexpression of PR and ER did not influence GPR30 expression, yet coexpression of GPR30 and ER was linked to PR positivity. Unlike ER, which varied inversely with HER-2/neu and tumor size, GPR30 positively associated with HER-2/neu and tumor size. In addition, GPR30 showed a positive association with metastasis (P=0.014; odds ratio, 1.9).


CONCLUSIONS
GPR30 and ER exhibited distinct patterns of association with breast tumor progression variables, including HER-2/neu, tumor size, and metastatic disease. Thus, these results support the hypothesis that GPR30 and ER have an independent influence on estrogen responsiveness in breast carcinoma.
Filardo
Edward J
EJ
Department of Medicine, Rhode Island Hospital, and Department of Pathology, Brown University School of Medicine, Providence, Rhode Island 02903, USA. edward_filardo@brown.edu
Graeber
Carl T
CT
Quinn
Jeffrey A
JA
Resnick
Murray B
MB
Giri
Dilip
D
DeLellis
Ronald A
RA
Steinhoff
Margaret M
MM
Sabo
Edmond
E
D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020893:Receptor, ErbB-3 / Q000378:metabolism; D011960:Receptors, Estrogen / Q000096:biosynthesis*; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis*; D011980:Receptors, Progesterone / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; C109584:GPER1 protein, human; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D011980:Receptors, Progesterone; D020893:Receptor, ErbB-3