Abstract
The role of intratumoural aromatase in human breast cancer growth remains controversial. At the same time as the use of aromatase inhibitors in the clinical setting continues to increase, so does the need for a tool to predict the likely response to this treatment. Intratumoural aromatase is a candidate predictive marker. The presently accepted 'gold standard' methods of assessment of aromatase activity are biochemical assays. However, these are time-consuming and require relatively large amounts of fresh or frozen tissue which are frequently not available. The development of a reliable immunohistochemical technique for the assessment of intratumoural aromatase which could be applied rapidly to more readily available paraffin-embedded material is therefore highly desirable. Unfortunately aromatase immunohistochemistry is also an area of controversy; some authors describe localisation to the stromal compartment but others to the malignant epithelial cells themselves. The aim of this study was therefore to compare immunohistochemical scores using two different antibodies with biochemical aromatase activity. Taking a group of 29 human breast carcinomas we demonstrated a strong correlation between immunoreactivity with a monoclonal antibody (p = 0.01) but not with a polyclonal (p = 0.16). The monoclonal produced reactivity in both epithelial and stromal cells but the polyclonal in only stromal cells. The implications of these results are discussed together with the need for further studies.
Similar content being viewed by others
References
James VHT, Reed MJ: Steroid hormones and human cancer. Prog Cancer Res Ther 14: 471–487, 1980
Silva MC, Rowlands MG, Dowsett M, Gusterson B, McKinna JA, Fryatt I, Coombes RC: Intratumoral aromatase as a prognostic factor in human breast carcinoma. Cancer Res 49: 2588–2591, 1989
Thorsen T, Tangen M, Stoa KF: Concentrations of endogenous estradiol as related to estradiol receptor sites in breast tumor cytosol. Eur J Cancer Clin Oncol 18: 333–337, 1982
van Landeghem AAJ, Portman J, Nabauura M: Endogenous concentration and subcellular distribution of estrogens in normal and malignant breast tissue. Cancer Res 45: 2900–2906, 1985
Bradlow HL: A reassessment of the role of breast tumor aromatisation. Cancer Res 42: 3382S–3386S, 1982
Masamura S, Santner SJ, Heitjan DF, Santen RJ: Estrogen deprivation causes estradiol hypersensitivity in human breast cancer cells. J Clin Endocrinol Metab 80: 2918–2925, 1995
Lu Q, Nakmura J, Savinov A, Yue W, Weisz J, Dabbs DJ, Wolz G, Brodie A: Expression of aromatase protein and messenger ribonucleic acid in tumor epithelial cells and evidence of functional significance of locally produced estrogen in human breast cancers. Endocrinol 137: 3061–3068, 1996
Miller WR, O'Neill J: The importance of local synthesis of estrogen within the breast. Steroids 50: 537–548, 1987
Miller WR: Importance of intratumoural aromatase, and its susceptibility to inhibitors. In: Dosett M (ed) Aromatase Inhibition — Then, Now and Tomorrow. Parthenon Publishing, New York, 1994, pp 43–53
Bezwoda WR, Mansoor N, Dansey R: Correlation of breast tumour aromatase activity and response to aromatase inhibition with aminoglutethimide. Oncology 44: 345–349, 1987
Sasano H, Nagura H, Harada N, Goukon Y, Kimura M: Immunolocalization of aromatase and other steroidogenic enzymes in human breast disorders. Human Pathol 25: 530–535, 1994
Santen RJ, Martel J, Hoahland F, Naftolin F, Roa L, Harada N, Hafer L, Zaino R, Santner SJ: Stromal spindle cells contain aromatase in human breast tumors. J Clin Endocrinol Metab 79: 627–632, 1994
Esteban JM, Warsi Z, Haniu M, Hall P, Shively JE, Chen S: Detection of intratumoral aromatase in breast carcinomas. Am J Pathol 140: 337–343, 1992
Jacobs TW, Prioleau JE, Stillman IE, Scnitt SJ: Loss of tumor marker-immunostaining intensity on stored paraffin slides of breast cancer. J Natl Cancer Inst 88: 1054–1059, 1996
Mendelson CR, Wright EE, Evans CT, Porter JC, Simpson ER: Preparation and characterization of polyclonal and monoclonal antibodies against human aromatase cytochrome P-450 (P-450AROM), and their use in its purification. Arch Biochem Biophys 243: 480–491, 1985
Harada N: Novel properties of human placental aromatase as cytochrome P-450: purification and characterization of a unique form of aromatase. J Biochem 103: 106–113, 1988
Detre S, Saccani Jotti G, Dowsett M: A ‘quickscore’ method for immunohistochemical semiquantitation: validation for oestrogen receptor in breast carcinomas. J Clin Pathol 48: 876–878, 1995
Hartree EF: Determination of protein: a modification of the Lowry method that gives a linear photometric response. Anal Biochem 48: 422–427, 1972
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Shenton, K., Dowsett, M., Lu, Q. et al. Comparison of biochemical aromatase activity with aromatase immunhistochemistry in human breast carcinomas. Breast Cancer Res Treat 49 (Suppl 1), S101–S107 (1998). https://doi.org/10.1023/A:1006033813899
Issue Date:
DOI: https://doi.org/10.1023/A:1006033813899