PMID- 9708807 OWN - NLM STAT- MEDLINE DCOM- 19980825 LR - 20240214 IS - 0002-9440 (Print) IS - 1525-2191 (Electronic) IS - 0002-9440 (Linking) VI - 153 IP - 2 DP - 1998 Aug TI - Cellular distribution of retinoic acid receptor-alpha protein in serous adenocarcinomas of ovarian, tubal, and peritoneal origin: comparison with estrogen receptor status. PG - 469-80 AB - 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. FAU - Katsetos, C D AU - Katsetos CD AD - Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA. dkatseto@bellatlantic.net FAU - Stadnicka, I AU - Stadnicka I FAU - Boyd, J C AU - Boyd JC FAU - Ehya, H AU - Ehya H FAU - Zheng, S AU - Zheng S FAU - Soprano, C M AU - Soprano CM FAU - Cooper, H S AU - Cooper HS FAU - Patchefsky, A S AU - Patchefsky AS FAU - Soprano, D R AU - Soprano DR FAU - Soprano, K J AU - Soprano KJ LA - eng GR - R01 CA064945/CA/NCI NIH HHS/United States GR - 3 RO1-CA64945-02S1/CA/NCI NIH HHS/United States GR - R01 CA64945/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Am J Pathol JT - The American journal of pathology JID - 0370502 RN - 0 (RARA protein, human) RN - 0 (Receptors, Estrogen) RN - 0 (Receptors, Retinoic Acid) RN - 0 (Retinoic Acid Receptor alpha) SB - IM MH - Adenocarcinoma/*metabolism/pathology MH - Adult MH - Aged MH - Aged, 80 and over MH - Blotting, Western MH - Fallopian Tube Neoplasms/*metabolism/pathology MH - Female MH - Humans MH - Immunoenzyme Techniques MH - Middle Aged MH - Neoplasms, Cystic, Mucinous, and Serous/metabolism/pathology MH - Ovarian Neoplasms/*metabolism/pathology MH - Peritoneal Neoplasms/*metabolism/pathology MH - Receptors, Estrogen/*metabolism MH - Receptors, Retinoic Acid/*metabolism MH - Retinoic Acid Receptor alpha PMC - PMC1852976 EDAT- 1998/08/26 00:00 MHDA- 1998/08/26 00:01 PMCR- 1999/02/01 CRDT- 1998/08/26 00:00 PHST- 1998/08/26 00:00 [pubmed] PHST- 1998/08/26 00:01 [medline] PHST- 1998/08/26 00:00 [entrez] PHST- 1999/02/01 00:00 [pmc-release] AID - S0002-9440(10)65590-3 [pii] AID - 1385 [pii] AID - 10.1016/s0002-9440(10)65590-3 [doi] PST - ppublish SO - Am J Pathol. 1998 Aug;153(2):469-80. doi: 10.1016/s0002-9440(10)65590-3.