Cellular Distribution of Retinoic Acid Receptor-alpha Protein in Serous Adenocarcinomas of Ovarian, Tubal, and Peritoneal Origin: Comparison with Estrogen Receptor Status

Overview

Journal Am J Pathol

Publisher Elsevier

Specialty Pathology

Date 1998 Aug 26

PMID 9708807

Citations 6

Authors

C D Katsetos

I Stadnicka

J C Boyd

H Ehya

S Zheng

C M Soprano

H S Cooper

A S Patchefsky

D R Soprano

K J Soprano

Affiliations

Soon will be listed here.

Abstract

Retinoids are effective growth modulators of human ovarian carcinoma cell lines. Their effects are mediated by nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which are transcriptional factors and members of the steroid/thyroid receptor superfamily. To our knowledge, until now, the cellular distribution of RAR proteins in human ovarian tumor specimens is unknown. This study provides new data on the differential cellular localization of RAR alpha protein in 16 serous adenocarcinomas originating from the ovaries, fallopian tubes, and the peritoneum. Using an affinity-purified antiserum specific for RAR alpha and a monoclonal antibody recognizing the full-length estrogen receptor molecule (clone 6F11), we performed immunohistochemistry on frozen tissue sections and examined the relationship between RAR alpha and estrogen receptor protein expression by comparing the percentage of immunostained tumor cells for either receptor. Our findings indicate a strong linear relationship between the percentages of RAR alpha- and estrogen receptor-labeled tumor cells as determined by linear regression analysis (P < 0.005, r = 0.825). A modest inverse relationship was found between the percentage of RAR alpha-positive tumor cells and histological grade, attesting to a differentiation-dependent trend (P < 0.04). No significant relationship was found between RAR alpha-labeled cells and clinical stage (P = 0.139), site of tumor origin (ovaries versus fallopian tubes versus peritoneum) (P = 0.170), and primary versus metastatic lesion (P = 0.561). Thus, serous adenocarcinomas are capable of expressing RAR alpha and estrogen receptor despite high histological grade and advanced stage of neoplastic disease. Compared with the heterogeneous localization of RAR alpha in cancer cells, there was widespread RAR alpha immunoreactivity in tumor-infiltrating lymphocytes, vascular endothelial cells, and stromal fibroblasts, underscoring the value of immunohistochemistry in the accurate determination of RAR/(RXR) content in tumor specimens.

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References

McGuire W . Steroid hormone receptors in breast cancer treatment strategy. Recent Prog Horm Res. 1980; 36:135-56. DOI: 10.1016/b978-0-12-571136-4.50010-3. View

Foyle A, McCAUGHEY W . Papillary peritoneal tumors in women. Am J Surg Pathol. 1981; 5(3):241-9. DOI: 10.1097/00000478-198104000-00004. View

Eifel P, Hendrickson M, Ross J, Ballon S, Martinez A, Kempson R . Simultaneous presentation of carcinoma involving the ovary and the uterine corpus. Cancer. 1982; 50(1):163-70. DOI: 10.1002/1097-0142(19820701)50:1<163::aid-cncr2820500131>3.0.co;2-k. View

Martin J, Hahnel R, McCartney A, Woodings T . The effect of estrogen receptor status on survival in patients with endometrial cancer. Am J Obstet Gynecol. 1983; 147(3):322-4. DOI: 10.1016/0002-9378(83)91119-5. View

Kaminski P, NORRIS H . Coexistence of ovarian neoplasms and endocervical adenocarcinoma. Obstet Gynecol. 1984; 64(4):553-6. View

Blaustein A . Peritoneal mesothelium and ovarian surface cells--shared characteristics. Int J Gynecol Pathol. 1984; 3(4):361-75. View

Schwartz P, MacLusky N, Merino M, Livolsi V, Kohorn E, Eisenfeld A . Are cytosol estrogen and progestin receptors of prognostic significance in the management of epithelial ovarian cancers?. Obstet Gynecol. 1986; 68(6):751-8. View

Das N, Ma C, Salmon Y . The relationship of serum vitamin A, cholesterol, and triglycerides to the incidence of ovarian cancer. Biochem Med Metab Biol. 1987; 37(2):213-9. DOI: 10.1016/0885-4505(87)90029-6. View

Slotman B, Rao B . Ovarian cancer (review). Etiology, diagnosis, prognosis, surgery, radiotherapy, chemotherapy and endocrine therapy. Anticancer Res. 1988; 8(3):417-34. View

10.

Langdon S, Hawkes M, Hay F, Lawrie S, Schol D, Hilgers J . Effect of sodium butyrate and other differentiation inducers on poorly differentiated human ovarian adenocarcinoma cell lines. Cancer Res. 1988; 48(21):6161-5. View

11.

Marth C, Helmberg M, Mayer I, Fuith L, Daxenbichler G, Dapunt O . Effects of biological response modifiers on ovarian carcinoma cell lines. Anticancer Res. 1989; 9(2):461-7. View

12.

Nervi C, Grippo J, Sherman M, George M, Jetten A . Identification and characterization of nuclear retinoic acid-binding activity in human myeloblastic leukemia HL-60 cells. Proc Natl Acad Sci U S A. 1989; 86(15):5854-8. PMC: 297729. DOI: 10.1073/pnas.86.15.5854. View

13.

Wick M, Mills S, Dehner L, Bollinger D, FECHNER R . Serous papillary carcinomas arising from the peritoneum and ovaries. A clinicopathologic and immunohistochemical comparison. Int J Gynecol Pathol. 1989; 8(3):179-88. DOI: 10.1097/00004347-198909000-00001. View

14.

Rose P, Piver M, Tsukada Y, Lau T . Metastatic patterns in histologic variants of ovarian cancer. An autopsy study. Cancer. 1989; 64(7):1508-13. DOI: 10.1002/1097-0142(19891001)64:7<1508::aid-cncr2820640725>3.0.co;2-v. View

15.

OMalley B . The steroid receptor superfamily: more excitement predicted for the future. Mol Endocrinol. 1990; 4(3):363-9. DOI: 10.1210/mend-4-3-363. View

16.

Cavey M, Martin B, Carlavan I, Shroot B . In vitro binding of retinoids to the nuclear retinoic acid receptor alpha. Anal Biochem. 1990; 186(1):19-23. DOI: 10.1016/0003-2697(90)90565-q. View

17.

Cooper H, Malecha M, Bass C, Fagel P, Steplewski Z . Expression of blood group antigens H-2, Le(y), and sialylated-Le(a) in human colorectal carcinoma. An immunohistochemical study using double-labeling techniques. Am J Pathol. 1991; 138(1):103-10. PMC: 1886064. View

18.

Leroy P, Krust A, Zelent A, Mendelsohn C, Garnier J, Kastner P . Multiple isoforms of the mouse retinoic acid receptor alpha are generated by alternative splicing and differential induction by retinoic acid. EMBO J. 1991; 10(1):59-69. PMC: 452611. DOI: 10.1002/j.1460-2075.1991.tb07921.x. View

19.

Slotman B, Baak J, Rao B . Correlation between nuclear DNA content and steroid receptor status in ovarian cancer. Eur J Obstet Gynecol Reprod Biol. 1991; 38(3):221-7. DOI: 10.1016/0028-2243(91)90296-w. View

20.

Rao B, Slotman B . Endocrine factors in common epithelial ovarian cancer. Endocr Rev. 1991; 12(1):14-26. DOI: 10.1210/edrv-12-1-14. View