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Protein in Serous Adenocarcinomas of Ovarian, Tubal, and Peritoneal Origin
From the Departments of Microbiology and Immunology*
and
Biochemistry,§
Temple University School of
Medicine, Philadelphia, Pennsylvania; Department of
Pathology,
University of Virginia Health
Sciences Center, Charlottesville, Virginia; and Department of
Pathology,
Fox Chase Cancer Center,
Philadelphia, Pennsylvania
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
protein in 16 serous adenocarcinomas originating
from the ovaries, fallopian tubes, and the peritoneum.
Using an affinity-purified antiserum specific for RAR 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 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- 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-positive tumor cells and histological
grade, attesting to a differentiation-dependent trend
(P < 0.04). No significant relationship was found
between RAR-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 and estrogen receptor despite high histological grade and
advanced stage of neoplastic disease. Compared with the heterogeneous
localization of RAR in cancer cells, there was widespread
RAR 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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