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Biomedical subjects

F Gorstein

Publications and source records attributed to F Gorstein.

At least 19 recordsLinked to original sources

Distribution of tumor-associated glycoprotein-72 (TAG-72) expression throughout the normal female reproductive tract.

Compared with the degree of investigation of stage-specific expression of tumor-associated glycoprotein-72 (TAG-72) in fundal endometrium, other regions of the female reproductive tract have not received comparable attention. Regional, cell-type-specific, and temporal differences in estrogen receptor and progesterone receptor distribution and concentration among these tissues should make such examination beneficial to our understanding of hormonal regulation of TAG-72 expression. The pattern of monoclonal antibody (MAb) B72.3 recognition in the cervix, uterus, oviduct, and ovary was examined by immunohistochemistry during both the proliferative and secretory intervals of the normal menstrual cycle. Intense immunoreactivity in fundal endometrium was limited to the secretory menstrual interval. Conversely, TAG-72 expression was generally weaker, sporadically distributed, and not stage specific in the lower uterine segment, endocervix, and cervix; no expression was detected in the oviduct or ovary. The disparity in both temporal and spatial distribution of TAG-72 expression throughout the female reproductive tract does not appear to be directly associated with the well-described changes in circulating estradiol or progesterone or the receptors for these steroids. Results suggest that regulation of TAG-72 expression may involve local paracrine/autocrine mechanisms, which in turn may be subject to hormonal influence.

Adult

Epithelial cells from normal human endometrium express a tumor-associated glycoprotein (TAG-72) epitope in vitro.

Monoclonal antibody B72.3 identifies a tumor-associated glycoprotein (TAG-72) epitope derived from a human breast carcinoma metastasis. Recently, expression of this epitope was noted in normal endometrium during the secretory, but not proliferative, menstrual interval. In light of known hormonal control of normal endometrial growth and differentiation, we investigated in vitro expression of TAG-72 epitope in purified endometrial epithelium cultured under serum-free conditions on Matrigel biomatrix. Cells from secretory endometrium exhibited homogeneous tumor-associated glycoprotein 72 epitope expression. Unexpectedly, epithelium from the proliferative interval developed expression after 5 to 6 days of culture. Epithelial cells from both intervals maintained expression over 12 days of culture without exogenous estradiol and progesterone. Spontaneous, uniform expression of tumor-associated glycoprotein 72 epitope by normal endometrial epithelial cells in vitro is in marked contrast to the cyclic, heterogeneous expression observed in vivo. Such expression also differs from published in vitro observations of cancer cell lines that express this epitope.

Antibodies, Monoclonal

Development of a method to isolate and culture highly purified populations of stromal and epithelial cells from human endometrial biopsy specimens.

Appropriate endometrial maturation is of paramount importance to achieve reproductive success. Practical and ethical considerations require that in vitro methods be available to evaluate regulation of human endometrial function. Additionally, tissue complexity requires separation of individual cell populations. This report describes an improved method for isolation of endometrial epithelial and stromal cells, using biopsy specimens as a tissue source. Separated cells were obtained using selective enzymatic digestion in conjunction with physical separation procedures. Isolated populations exhibited over 95% homogeneity, ascertained immunocytochemically. Using this system, isolated cells from normal endometrium can readily be obtained for in vitro studies. Within the defined conditions of a culture system, important areas of current concern in the endometrium such as ectopic endometrial growth and implantation can be addressed.

Adult

Adjunct to the diagnostic distinction between adenocarcinomas of the ovary and the colon utilizing a monoclonal antibody (COL-4) with restricted carcinoembryonic antigen reactivity.

Malignant ovarian tumors may represent either primary ovarian cancers or metastatic lesions (from patients with demonstrated primary cancers at other body sites) whose distinction may be difficult using clinical, surgical, and pathological criteria. Monoclonal antibody (MAb) COL-4, reactive with carcinoembryonic antigen, has previously been shown to react preferentially with adenocarcinomas of the colon versus a variety of normal tissues. We report here that MAb COL-4 is strongly reactive with primary colonic carcinomas (N = 50), as well as regional (N = 42), and distant (N = 20) metastases of colonic adenocarcinoma. In contrast, MAb COL-4 demonstrated little to no reactivity with primary (N = 53) and metastatic carcinomas of the ovary (N = 23) including serous, mucinous, and poorly differentiated adenocarcinomas using immunohistochemical techniques. This differential reactivity was statistically significant (P less than 0.001), suggesting the potential clinical utility of MAb COL-4 in the differentiation of ovarian from colonic adenocarcinoma. Solid-phase quantitative radioimmunoassays and Western blotting techniques confirmed these results. Data are also presented that the carcinoembryonic antigen molecules or epitopes recognized by a more classical broadly reactive anti-carcinoembryonic antigen MAb are distinct from those recognized by MAb COL-4. Other carcinomas which also metastasize to the ovary and may be confused clinically with a primary ovarian tumor such as adenocarcinomas of the stomach and breast were also evaluated for reactivity with MAb COL-4. COL-4 was also reactive with all gastric carcinomas evaluated, but failed to react with breast carcinomas. Hence, COL-4 can now be utilized as an immunohistochemical adjunct for the differentiation of ovarian from gastrointestinal adenocarcinoma which can be difficult to distinguish by clinical, surgical, and histological parameters.

Adenocarcinoma

Monoclonal antibody B72.3 reactivity with human endometrium: a study of normal and malignant tissues.

Monoclonal antibody (MAb) B72.3, reactive with a high molecular weight mucin-like glycoprotein [termed tumor-associated glycoprotein (TAG)-72], has been shown previously to react preferentially with adenocarcinomas of the ovary, breast, and colon versus a variety of normal human tissues using immunohistochemical and radioimmunoassay (RIA) techniques. We report here B72.3 reactivity with normal postovulatory endometria, in contrast to proliferative phase epithelia that were nonreactive. Both immunohistochemical and RIA techniques were used to evaluate this phenomenon. TAG-72 expression was also detected in 100% of endometrial adenocarcinomas (n = 32) examined. No MAb B72.3 reactivity was noted in resting, postmenopausal endometria; however, it was present in hyperplastic lesions and appeared to correlate with the severity of histologic abnormality. The utility of MAb B72.3 for screening, radiolocalization, or perhaps therapy of endometrial adenocarcinoma is also discussed.

Adenocarcinoma

Tumor-associated glycoprotein (TAG-72) in ovarian carcinomas defined by monoclonal antibody B72.3.

Murine IgG1 monoclonal antibody (MoAb) B72.3, reactive with a high molecular weight glycoprotein complex [designated tumor-associated glycoprotein-72 (TAG-72)] was shown, with the use of the avidin-biotin-complex-immunoperoxidase technique and surgically resected tissues, to be reactive with a variety of histologic tumor types. TAG-72 is expressed in at least 5% (and up to 100%) of the malignant epithelial cells in 77% (n = 52) of human primary cancers and 71% (n = 31) of metastatic ovarian cancers of the common "epithelia" histologic category. Of these, several histologic types, including serous and mucinous cystadenocarcinomas, undifferentiated carcinomas, and less common types of ovarian carcinoma, were all shown to express TAG-72. In contrast, normal ovarian tissues and 26 of 27 benign ovarian tumors of various histologic types failed to express similar levels of TAG-72. Of interest is the 1 benign tumor that demonstrated unusual glandular complexity, as well as 3 tumors designated as borderline malignancy, that contained elevated TAG-72 expression. MoAb B72.3 also was used successfully to detect ovarian carcinoma cells in 28 cytologic preparations of human serous effusions and peritoneal washings. The reactivity of MoAb B72.3 was shown to be distinct from that of MoAb OC125 and an anti-CEA MoAb B1.1. The potential applications of MoAb B72.3 in the study of human ovarian cancer cell populations, as well as in several aspects of the management of human ovarian cancer, are discussed.

Animals