Abstract
The expression of 17β-hydroxysteroid dehydrogenase (17β-HSD) type 1 and type 2 was examined immunohistochemically in 111 invasive ductal carcinomas, and correlated with various clinicopathological parameters. This study investigates local regulatory mechanisms of oestrogens in human breast carcinoma. 17β-HSD type 1 was immunolocalized in carcinoma cells of 68 out of 111 invasive ductal carcinoma cases (61.3%). 17β-HSD type 2 immunoreactivity was not detected in all cases examined. A significant inverse correlation was observed between the immunohistochemical expression of 17β-HSD type 1 and histological grade of the carcinoma (P< 0.02). There was a significant correlation between 17β-HSD type 1 and oestrogen receptor (ER) labelling index (LI) (P< 0.05). In addition, carcinoma cells expressing immunoreactive 17β-HSD type 1 were frequently positive for ER. 17β-HSD type 1 was also correlated with progesterone receptor (PR) LI (P< 0.05). There was a significant inverse correlation between 17β-HSD type 1 and Ki-67 LI (P< 0.0001). No significant correlations were detected between 17β-HSD type 1 and other clinicopathological parameters, including patient age, menopausal status, stage, tumour size, lymph node status and prognosis. This study suggests that 17β-HSD type 1 plays an important role in the regulation of in situ oestradiol production in hormone-dependent breast carcinomas. © 2000 Cancer Research Campaign
Keywords: 17β-HSD, breast, carcinoma, human, immunohistochemistry, oestrogen
Full Text
The Full Text of this article is available as a PDF (237.1 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adams E. F., Coldham N. G., James V. H. Steroidal regulation of oestradiol-17 beta dehydrogenase activity of the human breast cancer cell line MCF-7. J Endocrinol. 1988 Jul;118(1):149–154. doi: 10.1677/joe.0.1180149. [DOI] [PubMed] [Google Scholar]
- BLOOM H. J., RICHARDSON W. W. Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years. Br J Cancer. 1957 Sep;11(3):359–377. doi: 10.1038/bjc.1957.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bonney R. C., Reed M. J., Davidson K., Beranek P. A., James V. H. The relationship between 17 beta-hydroxysteroid dehydrogenase activity and oestrogen concentrations in human breast tumours and in normal breast tissue. Clin Endocrinol (Oxf) 1983 Dec;19(6):727–739. doi: 10.1111/j.1365-2265.1983.tb00051.x. [DOI] [PubMed] [Google Scholar]
- Brown D. C., Gatter K. C. Monoclonal antibody Ki-67: its use in histopathology. Histopathology. 1990 Dec;17(6):489–503. doi: 10.1111/j.1365-2559.1990.tb00788.x. [DOI] [PubMed] [Google Scholar]
- Casey M. L., MacDonald P. C., Andersson S. 17 beta-Hydroxysteroid dehydrogenase type 2: chromosomal assignment and progestin regulation of gene expression in human endometrium. J Clin Invest. 1994 Nov;94(5):2135–2141. doi: 10.1172/JCI117569. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Elston C. W., Ellis I. O. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991 Nov;19(5):403–410. doi: 10.1111/j.1365-2559.1991.tb00229.x. [DOI] [PubMed] [Google Scholar]
- Fournier S., Brihmat F., Durand J. C., Sterkers N., Martin P. M., Kuttenn F., Mauvais-Jarvis P. Estradiol 17 beta-hydroxysteroid dehydrogenase, a marker of breast cancer hormone dependency. Cancer Res. 1985 Jun;45(6):2895–2899. [PubMed] [Google Scholar]
- Gast M. J., Sims H. F., Murdock G. L., Gast P. M., Strauss A. W. Isolation and sequencing of a complementary deoxyribonucleic acid clone encoding human placental 17 beta-estradiol dehydrogenase: identification of the putative cofactor binding site. Am J Obstet Gynecol. 1989 Dec;161(6 Pt 1):1726–1731. doi: 10.1016/0002-9378(89)90958-7. [DOI] [PubMed] [Google Scholar]
- Gerdes J., Schwab U., Lemke H., Stein H. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer. 1983 Jan 15;31(1):13–20. doi: 10.1002/ijc.2910310104. [DOI] [PubMed] [Google Scholar]
- James V. H., Reed M. J., Folkerd E. J. Studies of oestrogen metabolism in postmenopausal women with cancer. J Steroid Biochem. 1981 Dec;15:235–245. doi: 10.1016/0022-4731(81)90280-6. [DOI] [PubMed] [Google Scholar]
- Leszczynski D., Santner S. J., Feil P. D., Santen R. J. 17 Beta-hydroxysteroid dehydrogenase in human breast cancer: analysis of kinetic and clinical parameters. Steroids. 1988 Mar-Apr;51(3-4):299–316. doi: 10.1016/0039-128x(88)90020-7. [DOI] [PubMed] [Google Scholar]
- Luu The V., Labrie C., Zhao H. F., Couët J., Lachance Y., Simard J., Leblanc G., Côté J., Bérubé D., Gagné R. Characterization of cDNAs for human estradiol 17 beta-dehydrogenase and assignment of the gene to chromosome 17: evidence of two mRNA species with distinct 5'-termini in human placenta. Mol Endocrinol. 1989 Aug;3(8):1301–1309. doi: 10.1210/mend-3-8-1301. [DOI] [PubMed] [Google Scholar]
- Marrazzo A., La Bara G., Taormina P., Bazan P. Determination of oestrogen receptors with monoclonal antibodies in fine needle aspirates of breast carcinoma. Br J Cancer. 1989 Mar;59(3):426–428. doi: 10.1038/bjc.1989.86. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miettinen M. M., Mustonen M. V., Poutanen M. H., Isomaa V. V., Vihko R. K. Human 17 beta-hydroxysteroid dehydrogenase type 1 and type 2 isoenzymes have opposite activities in cultured cells and characteristic cell- and tissue-specific expression. Biochem J. 1996 Mar 15;314(Pt 3):839–845. doi: 10.1042/bj3140839. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miller W. R. Aromatase activity in breast tissue. J Steroid Biochem Mol Biol. 1991 Nov;39(5B):783–790. doi: 10.1016/0960-0760(91)90026-2. [DOI] [PubMed] [Google Scholar]
- Moghrabi N., Head J. R., Andersson S. Cell type-specific expression of 17 beta-hydroxysteroid dehydrogenase type 2 in human placenta and fetal liver. J Clin Endocrinol Metab. 1997 Nov;82(11):3872–3878. doi: 10.1210/jcem.82.11.4391. [DOI] [PubMed] [Google Scholar]
- Peltoketo H., Isomaa V., Mäentausta O., Vihko R. Complete amino acid sequence of human placental 17 beta-hydroxysteroid dehydrogenase deduced from cDNA. FEBS Lett. 1988 Oct 24;239(1):73–77. doi: 10.1016/0014-5793(88)80548-9. [DOI] [PubMed] [Google Scholar]
- Pollow K., Boquoi E., Baumann J., Schmidt-Gollwitzer M., Pollow B. Comparison of the in vitro conversion of estradiol-17 beta to estrone of normal and neoplastic human breast tissue. Mol Cell Endocrinol. 1977 Feb;6(4-5):333–348. doi: 10.1016/0303-7207(77)90108-3. [DOI] [PubMed] [Google Scholar]
- Poutanen M., Isomaa V., Kainulainen K., Vihko R. Progestin induction of 17 beta-hydroxysteroid dehydrogenase enzyme protein in the T-47D human breast-cancer cell line. Int J Cancer. 1990 Nov 15;46(5):897–901. doi: 10.1002/ijc.2910460524. [DOI] [PubMed] [Google Scholar]
- Poutanen M., Isomaa V., Lehto V. P., Vihko R. Immunological analysis of 17 beta-hydroxysteroid dehydrogenase in benign and malignant human breast tissue. Int J Cancer. 1992 Feb 1;50(3):386–390. doi: 10.1002/ijc.2910500310. [DOI] [PubMed] [Google Scholar]
- Poutanen M., Moncharmont B., Vihko R. 17 beta-hydroxysteroid dehydrogenase gene expression in human breast cancer cells: regulation of expression by a progestin. Cancer Res. 1992 Jan 15;52(2):290–294. [PubMed] [Google Scholar]
- Reiner A., Reiner G., Spona J., Schemper M., Holzner J. H. Histopathologic characterization of human breast cancer in correlation with estrogen receptor status. A comparison of immunocytochemical and biochemical analysis. Cancer. 1988 Mar 15;61(6):1149–1154. doi: 10.1002/1097-0142(19880315)61:6<1149::aid-cncr2820610615>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
- Rose C., Thorpe S. M., Mouridsen H. T., Andersen J. A., Brincker H., Andersen K. W. Antiestrogen treatment of postmenopausal women with primary high risk breast cancer. Breast Cancer Res Treat. 1983;3(1):77–84. doi: 10.1007/BF01806237. [DOI] [PubMed] [Google Scholar]
- Sasano H., Frost A. R., Saitoh R., Harada N., Poutanen M., Vihko R., Bulun S. E., Silverberg S. G., Nagura H. Aromatase and 17 beta-hydroxysteroid dehydrogenase type 1 in human breast carcinoma. J Clin Endocrinol Metab. 1996 Nov;81(11):4042–4046. doi: 10.1210/jcem.81.11.8923858. [DOI] [PubMed] [Google Scholar]
- Sasano H., Nagura H., Harada N., Goukon Y., Kimura M. Immunolocalization of aromatase and other steroidogenic enzymes in human breast disorders. Hum Pathol. 1994 May;25(5):530–535. doi: 10.1016/0046-8177(94)90127-9. [DOI] [PubMed] [Google Scholar]
- Suzuki T., Sasano H., Kimura N., Tamura M., Fukaya T., Yajima A., Nagura H. Immunohistochemical distribution of progesterone, androgen and oestrogen receptors in the human ovary during the menstrual cycle: relationship to expression of steroidogenic enzymes. Hum Reprod. 1994 Sep;9(9):1589–1595. doi: 10.1093/oxfordjournals.humrep.a138757. [DOI] [PubMed] [Google Scholar]
- Suzuki T., Sasano H., Takaya R., Fukaya T., Yajima A., Nagura H. Cyclic changes of vasculature and vascular phenotypes in normal human ovaries. Hum Reprod. 1998 Apr;13(4):953–959. doi: 10.1093/humrep/13.4.953. [DOI] [PubMed] [Google Scholar]
- Takeyama J., Sasano H., Suzuki T., Iinuma K., Nagura H., Andersson S. 17Beta-hydroxysteroid dehydrogenase types 1 and 2 in human placenta: an immunohistochemical study with correlation to placental development. J Clin Endocrinol Metab. 1998 Oct;83(10):3710–3715. doi: 10.1210/jcem.83.10.5212. [DOI] [PubMed] [Google Scholar]
- Thomas D. B. Do hormones cause breast cancer? Cancer. 1984 Feb 1;53(3 Suppl):595–604. doi: 10.1002/1097-0142(19840201)53:3+<595::aid-cncr2820531304>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]
- Veronese S. M., Gambacorta M. Detection of Ki-67 proliferation rate in breast cancer. Correlation with clinical and pathologic features. Am J Clin Pathol. 1991 Jan;95(1):30–34. doi: 10.1093/ajcp/95.1.30. [DOI] [PubMed] [Google Scholar]
- Veronese S. M., Gambacorta M., Gottardi O., Scanzi F., Ferrari M., Lampertico P. Proliferation index as a prognostic marker in breast cancer. Cancer. 1993 Jun 15;71(12):3926–3931. doi: 10.1002/1097-0142(19930615)71:12<3926::aid-cncr2820711221>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
- Wu L., Einstein M., Geissler W. M., Chan H. K., Elliston K. O., Andersson S. Expression cloning and characterization of human 17 beta-hydroxysteroid dehydrogenase type 2, a microsomal enzyme possessing 20 alpha-hydroxysteroid dehydrogenase activity. J Biol Chem. 1993 Jun 15;268(17):12964–12969. [PubMed] [Google Scholar]