Beta-hCG/LH receptor (b-HCG/LH-R) expression is increased in invasive versus preinvasive breast cancer: implications for breast carcinogenesis?
- 152 Downloads
The role of the b-HCG/LH/LH-R system in breast cancer is conflicting. Whereas some reports suggest a protective effect of b-HCG on breast epithelium, vitro studies implicate a role of b-HCG/LH-R in the development and growth of breast tumors.
Material and methods
In order to further investigate a possible involvement of b-HCG/LH-R in breast carcinogenesis, immunofluorescence analyses of b-HCG/LH-R expression was performed on 70 preinvasive and adjacent invasive breast cancer specimen using tissue microarrays (TMAs).
In 37 preinvasive samples available for further analysis, b-HCG/LH-R was found in 8/37 samples (21.6%; weak, intermediate and strong staining in 4/37 (10.8%), 2/37 (5.4%) and 2/37 (5.4%). In contrast, b-HCG/LH-R expression was observed in 19/27 (70.4%) adjacent invasive specimen with weak, moderate and strong immunostaining in 10/27 (37.0%), 6/27 (22.2%) and 3/27 (11.1%), respectively. This was statistically significant when compared to preinvasive components (P = 0.001, Chi Square Test).
Based on the observation that b-HCG/LH-R was found to be selectively upregulated in invasive tumor components, we suggest that under certain circumstances, sensitivity of ductal cells to hormones that target b-HCG/LH-R could favour mammary carcinogenesis.
KeywordsHCG receptor Breast cancer DCIS Invasive
The authors wish to thank Barbara Weidinger and Martha Weinhaeusl for technical assistance with the immunohistochemical procedures.
- Hudelist G, Huber A, Knoefler M, et al (2008) Human chorionic gonadotropin/luteinizing hormone receptor (HCG/LH-R) expression in eutopic endometrium and endometriotic implants: evidence for HCG sensitivity of endometriosis. Reprod Sci 15(6):543–551Google Scholar
- Kuorelahti A, Rulli S, Huhtaniemi I, Poutanen M (2007) Human chorionic gonadotropin (hCG) up-regulates wnt5b and wnt7b in the mammary gland, and hCGbeta transgenic female mice present with mammary Gland tumors exhibiting characteristics of the Wnt/beta-catenin pathway activation. Endocrinology 148:3694–3703. doi: 10.1210/en.2007-0249 PubMedCrossRefGoogle Scholar
- Lojun S, Bao S, Lei ZM, Rao CV (1997) Presence of functional luteinizing hormone/chorionic gonadotropin (hCG) receptors in human breast cell lines: implications supporting the premise that hCG protects women against breast cancer. Biol Reprod 57:1202–1210. doi: 10.1095/biolreprod57.5.1202 PubMedCrossRefGoogle Scholar
- Mann RJ, Keri RA, Nilson JH (2003) Consequences of elevated luteinizing hormone on diverse physiological systems: use of the LHbetaCTP transgenic mouse as a model of ovarian hyperstimulation-induced pathophysiology. Recent Prog Horm Res 58:343–375. doi: 10.1210/rp.58.1.343 PubMedCrossRefGoogle Scholar
- Piersma D, Berns EM, Verhoef-Post M et al (2006) A common polymorphism renders the luteinizing hormone receptor protein more active by improving signal peptide function and predicts adverse outcome in breast cancer patients. J Clin Endocrinol Metab 91:1470–1476. doi: 10.1210/jc.2005-2156 PubMedCrossRefGoogle Scholar
- Rulli SB, Kuorelahti A, Karaer O, Pelliniemi LJ, Poutanen M, Huhtaniemi I (2002) Reproductive disturbances, pituitary lactotrope adenomas, and mammary gland tumors in transgenic female mice producing high levels of human chorionic gonadotropin. Endocrinology 143:4084–4095. doi: 10.1210/en.2002-220490 PubMedCrossRefGoogle Scholar
- Shemesh M, Mizrachi D, Gurevich M et al (2001) Expression of functional luteinizing hormone (LH) receptor and its messenger ribonucleic acid in bovine endometrium: LH augmentation of cAMP and inositol phosphate in vitro and human chorionic gonadotropin (hCG) augmentation of peripheral prostaglandin in vivo. Reprod Biol 1:13–32PubMedGoogle Scholar