Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1996 Jul;149(1):45–51.

Aromatase in human common epithelial ovarian neoplasms.

K Kaga 1, H Sasano 1, N Harada 1, M Ozaki 1, S Sato 1, A Yajima 1
PMCID: PMC1865210  PMID: 8686761

Abstract

The expression of aromatase was evaluated in 44 ovarian carcinomas, 7 carcinomas of low malignant potential (LMP), and 14 benign adenomas. Aromatase immunoreactivity was observed in stromal cells in 35 of 44 (79.5%) ovarian carcinomas and 3 of 7 carcinomas of LMP. However, no immunoreactivity was pronounced at sites of frank invasion in ovarian carcinoma. To characterize aromatase in ovarian carcinoma, aromatase activity, mRNA expression, and alternative uses of exon 1 were determined. Quantitation of aromatase activity with the tritiated water method demonstrated 41.62 +/- 9.15 pmol/hour/mg protein in 11 ovarian carcinomas. The mean concentration of aromatase mRNA for 14 ovarian carcinomas was 3 +/- 4 amol/ng RNA, which significantly correlated with aromatase immunoreactivity. The alternative use of multiple copies of exon 1 was examined by reverse transcriptase polymerase chain reaction in 11 carcinomas. The transcript, mainly using exons 1c and 1d, was detected in 4 and 5 cases of carcinoma, respectively. Patterns of utilization of exon 1, however, did not significantly correlate with aromatase overexpression. These results suggest that aromatase is expressed in stromal cells of ovarian carcinoma but not in benign ovarian neoplasms. Increased aromatase expression in stromal cells of human ovarian carcinoma is, therefore, considered to play an important role in the biological behavior of these tumors by producing estrogens in situ as in other female sex-steroid-dependent neoplasms.

Full text

PDF
45

Images in this article

48Figure 2
on p.48

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bulun S. E., Economos K., Miller D., Simpson E. R. CYP19 (aromatase cytochrome P450) gene expression in human malignant endometrial tumors. J Clin Endocrinol Metab. 1994 Dec;79(6):1831–1834. doi: 10.1210/jcem.79.6.7989490. [DOI] [PubMed] [Google Scholar]
  2. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  3. Cramer D. W., Welch W. R. Determinants of ovarian cancer risk. II. Inferences regarding pathogenesis. J Natl Cancer Inst. 1983 Oct;71(4):717–721. [PubMed] [Google Scholar]
  4. Doody K. J., Lorence M. C., Mason J. I., Simpson E. R. Expression of messenger ribonucleic acid species encoding steroidogenic enzymes in human follicles and corpora lutea throughout the menstrual cycle. J Clin Endocrinol Metab. 1990 Apr;70(4):1041–1045. doi: 10.1210/jcem-70-4-1041. [DOI] [PubMed] [Google Scholar]
  5. Harada N. Novel properties of human placental aromatase as cytochrome P-450: purification and characterization of a unique form of aromatase. J Biochem. 1988 Jan;103(1):106–113. doi: 10.1093/oxfordjournals.jbchem.a122213. [DOI] [PubMed] [Google Scholar]
  6. Harada N., Utsumi T., Takagi Y. Tissue-specific expression of the human aromatase cytochrome P-450 gene by alternative use of multiple exons 1 and promoters, and switching of tissue-specific exons 1 in carcinogenesis. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11312–11316. doi: 10.1073/pnas.90.23.11312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Harada N., Yamada K., Foidart A., Balthazart J. Regulation of aromatase cytochrome P-450 (estrogen synthetase) transcripts in the quail brain by testosterone. Brain Res Mol Brain Res. 1992 Sep;15(1-2):19–26. doi: 10.1016/0169-328x(92)90146-3. [DOI] [PubMed] [Google Scholar]
  8. Harada N., Yamada K. Ontogeny of aromatase messenger ribonucleic acid in mouse brain: fluorometrical quantitation by polymerase chain reaction. Endocrinology. 1992 Nov;131(5):2306–2312. doi: 10.1210/endo.131.5.1425429. [DOI] [PubMed] [Google Scholar]
  9. Inkster S. E., Brodie A. M. Expression of aromatase cytochrome P-450 in premenopausal and postmenopausal human ovaries: an immunocytochemical study. J Clin Endocrinol Metab. 1991 Oct;73(4):717–726. doi: 10.1210/jcem-73-4-717. [DOI] [PubMed] [Google Scholar]
  10. Jeppsson S., Karlsson S., Kullander S. Gonadal steroids, gonadotropins and endometrial histology in postmenopausal women with malignant ovarian tumors. Acta Obstet Gynecol Scand. 1986;65(3):207–210. doi: 10.3109/00016348609155172. [DOI] [PubMed] [Google Scholar]
  11. Kitawaki J., Inoue S., Tamura T., Yamamoto T., Noguchi T., Osawa Y., Okada H. Increasing aromatase cytochrome P-450 level in human placenta during pregnancy: studied by immunohistochemistry and enzyme-linked immunosorbent assay. Endocrinology. 1992 May;130(5):2751–2757. doi: 10.1210/endo.130.5.1572292. [DOI] [PubMed] [Google Scholar]
  12. Lephart E. D., Simpson E. R., McPhaul M. J. Ovarian aromatase cytochrome P-450 mRNA levels correlate with enzyme activity and serum estradiol levels in anestrous, pregnant and lactating rats. Mol Cell Endocrinol. 1992 Jun;85(3):205–214. doi: 10.1016/0303-7207(92)90259-9. [DOI] [PubMed] [Google Scholar]
  13. MacDonald P. C., Grodin J. M., Edman C. D., Vellios F., Siiteri P. K. Origin of estrogen in a postmenopausal woman with a nonendocrine tumor of the ovary and endometrial hyperplasia. Obstet Gynecol. 1976 Jun;47(6):644–650. [PubMed] [Google Scholar]
  14. MacLusky N. J., Voit R., Lazo J. S., Schwartz P. E., Merino M. J., Eisenfeld A. E., Naftolin F. Aromatase activity in human ovarian cancer. Steroids. 1987 Oct-Dec;50(4-6):423–433. doi: 10.1016/0039-128x(87)90029-8. [DOI] [PubMed] [Google Scholar]
  15. Noguchi T., Kitawaki J., Tamura T., Kim T., Kanno H., Yamamoto T., Okada H. Relationship between aromatase activity and steroid receptor levels in ovarian tumors from postmenopausal women. J Steroid Biochem Mol Biol. 1993 Mar;44(4-6):657–660. doi: 10.1016/0960-0760(93)90275-2. [DOI] [PubMed] [Google Scholar]
  16. Rao B. R., Slotman B. J. Endocrine factors in common epithelial ovarian cancer. Endocr Rev. 1991 Feb;12(1):14–26. doi: 10.1210/edrv-12-1-14. [DOI] [PubMed] [Google Scholar]
  17. Rutgers J. L., Scully R. E. Functioning ovarian tumors with peripheral steroid cell proliferation: a report of twenty-four cases. Int J Gynecol Pathol. 1986;5(4):319–337. doi: 10.1097/00004347-198612000-00004. [DOI] [PubMed] [Google Scholar]
  18. SCULLY R. E., COHEN R. B. OXIDATIVE-ENZYME ACTIVITY IN NORMAL AND PATHOLOGIC HUMAN OVARIES. Obstet Gynecol. 1964 Nov;24:667–681. [PubMed] [Google Scholar]
  19. Sasano H., Fukunaga M., Rojas M., Silverberg S. G. Hyperthecosis of the ovary. Clinicopathologic study of 19 cases with immunohistochemical analysis of steroidogenic enzymes. Int J Gynecol Pathol. 1989;8(4):311–320. [PubMed] [Google Scholar]
  20. 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]
  21. Sasano H., Okamoto M., Mason J. I., Simpson E. R., Mendelson C. R., Sasano N., Silverberg S. G. Immunohistochemical studies of steroidogenic enzymes (aromatase, 17 alpha-hydroxylase and cholesterol side-chain cleavage cytochromes P-450) in sex cord-stromal tumors of the ovary. Hum Pathol. 1989 May;20(5):452–457. doi: 10.1016/0046-8177(89)90010-5. [DOI] [PubMed] [Google Scholar]
  22. Slotman B. J., Kühnel R., Rao B. R., Dijkhuizen G. H., de Graaff J., Stolk J. G. Importance of steroid receptors and aromatase activity in the prognosis of ovarian cancer: high tumor progesterone receptor levels correlate with longer survival. Gynecol Oncol. 1989 Apr;33(1):76–81. doi: 10.1016/0090-8258(89)90607-0. [DOI] [PubMed] [Google Scholar]
  23. Stadel B. V. Letter: The etiology and prevention of ovarian cancer. Am J Obstet Gynecol. 1975 Dec 1;123(7):772–774. doi: 10.1016/0002-9378(75)90509-8. [DOI] [PubMed] [Google Scholar]
  24. Suzuki T., Sasano H., Sasaki H., Fukaya T., Nagura H. Quantitation of P450 aromatase immunoreactivity in human ovary during the menstrual cycle: relationship between the enzyme activity and immunointensity. J Histochem Cytochem. 1994 Dec;42(12):1565–1573. doi: 10.1177/42.12.7983357. [DOI] [PubMed] [Google Scholar]
  25. Thompson E. A., Jr, Siiteri P. K. Utilization of oxygen and reduced nicotinamide adenine dinucleotide phosphate by human placental microsomes during aromatization of androstenedione. J Biol Chem. 1974 Sep 10;249(17):5364–5372. [PubMed] [Google Scholar]
  26. Watanabe K., Sasano H., Harada N., Ozaki M., Niikura H., Sato S., Yajima A. Aromatase in human endometrial carcinoma and hyperplasia. Immunohistochemical, in situ hybridization, and biochemical studies. Am J Pathol. 1995 Feb;146(2):491–500. [PMC free article] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES