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Biomedical subjects

C F Holinka

Publications and source records attributed to C F Holinka.

At least 19 recordsLinked to original sources
PubMed2006

Differential prevalence of quality-of-life categories (domains) in Asian women and changes after therapy with three doses of conjugated estrogens/medroxyprogesterone acetate: the Pan-Asia Menopause (PAM) study.

OBJECTIVES: To assess the prevalence of four categories (domains) of menopausal symptoms as markers for quality of life in nine ethnic groups of Asian women. To evaluate changes in quality of life (MENQOL scores) in Asian women following hormone therapy. METHODS: A prospective, randomized, double-blind, multinational clinical trial in 1028 healthy postmenopausal women of nine ethnic groups from 11 Asian countries/regions. Following 2 weeks of baseline observation, the women received one of three conjugated estrogens (CE)/medroxyprogesterone acetate (MPA) doses (in mg) daily for 24 weeks: 0.625/2.5, 0.45/1.5, or 0.3/1.5. At baseline and at the end of weeks 4, 12 and 24 following the start of therapy, the study participants were asked to record, on a menopause-specific quality of life (MENQOL) questionnaire, 29 menopausal symptoms, as experienced during the preceding month. The symptoms were categorized into four domains: vasomotor, psychosocial, physical and sexual. RESULTS: The baseline (pretreatment) symptom scores in each of the four domains varied substantially among the different ethnic groups, ranging from 2.21 to 5.71 in the vasomotor, 2.37-5.96 in the psychosocial, 2.66-5.39 in the physical, and 2.11-6.55 in the sexual domain. Overall, Vietnamese and Pakistani women had the highest baseline scores, i.e. were most afflicted by each set of symptoms in a given domain, and Indonesian, Malay, Taiwanese and Thai women were least afflicted. In the overall population, intervention resulted in statistically significant decreases in the scores of all four domains within 4 weeks of intervention. The beneficial effects were similar in the three dose groups. CONCLUSIONS: The prevalence of four domains of menopausal symptoms, representative of quality of life as recorded on a MENQOL questionnaire, varies considerably among ethnic groups of Asian women. The MENQOL scores in the overall population were significantly lowered in the course of the study, indicating an improvement in quality of life. In the absence of a placebo group, the relative contribution of hormones and placebo in our intervention is unknown.

Adult↗
PubMed2001

Design and conduct of clinical trials in hormone replacement therapy.

Postmenopausal hormone replacement therapy represents an area of outstanding importance in preventive medicine that greatly affects personal well-being as well as public health. The number of women living in the United States who are 50 years or older has been estimated at nearly 50 million. Many of those women are likely to be eligible for postmenopausal hormone replacement, which may consist either of estrogen replacement therapy (ERT) in women without a uterus or, more frequently, estrogen/progestin combination therapy (HRT) in women with a uterus. This chapter first presents an overview of general regulatory requirements pertaining to the design and conduct of clinical studies in support of marketing approval for a drug product. These requirements include, but are not restricted to, studies in HRT. The chapter next discusses the design and conduct of clinical trials in support of marketing approval for the indications: treatment of moderate to severe vasomotor symptoms and vulvovaginal atrophy; prevention of osteoporosis; and protection by adjunctive progestin against estrogen-induced endometrial hyperplasia/cancer in women with a uterus. Finally, data related to the potential cardioprotective action of HRT and its protection against Alzheimer's disease and colon cancer are discussed.

Animals↗
PubMed1997

Transdermal sequential and continuous hormone replacement regimens with estradiol and norethisterone acetate in postmenopausal women: effects on the endometrium.

OBJECTIVE: To evaluate, in postmenopausal women, the endometrial safety and histologic effects of two doses of transdermal norethisterone acetate (NETA) administered in sequential and continuous treatment regimens added to continuous transdermal estradiol, against a reference regimen consisting of sequential oral progestogen and continuous transdermal estradiol. METHODS: A total of 774 postmenopausal women were enrolled in the open-label study of 13 treatment cycles of 28 days each and randomly assigned evenly to regimens consisting of transdermal estradiol, 50 micrograms/day and NETA, given sequentially (last 14 days of each treatment cycle) or continuously at two doses (170 and 350 micrograms/day). Estradiol and NETA were delivered from a transdermal system containing both hormones. The reference group received estradiol, 50 micrograms/day transdermally and either 1 mg/day NET or 20 mg/day dydrogesterone orally during the last 14 days of each treatment cycle. Endometrial biopsies were taken pre-study and at the end of the treatment, if treatment had lasted at least 3 months. Safety was to be assessed in terms of the incidence of hyperplasia. Endometrial biopsies were assigned to one of the following histological classes: proliferative (predominant estrogen effect), suppressed proliferation (slightly, moderately, strongly progestogenic effect), progestational atrophy (predominant progestogenic effect), hyperplastic, cancerous, or other. RESULTS: No case of hyperplasia was recorded in any of the treatment groups, each with > 150 subjects enrolled, after one year of treatment. One case of serous carcinoma was found in the LP-C group. Progestational atrophy was seen frequently in women receiving continuous transdermal HRT (84%, high-dose NETA, 66%, low-dose NETA); it was much rarer with the sequential regimens (i.e., between 32% and 38%). The proportion of estrogen-dominated endometria was low, 0.9% and 2.6% with the high- and low-dose NETA continuous regimens, respectively, 6.2% and 12.5% with the high- and low-dose NETA sequential regimens, respectively; and, 4.5% in the oral progestogen group. CONCLUSION: Transdermal administration of either dose of NETA, whether given sequentially or continuously, prevents the emergence of hyperplasia expected with unopposed estradiol. Since differences in outcomes of endometrial histology between the two NETA doses were minor for both continuous and sequential regimens, use of the lower NETA dose is considered sufficient for a safe transdermal combination hormone replacement therapy.

Administration, Cutaneous↗
PubMed1994

Aspects of hormone replacement therapy.

The most important benefit of ERT may well be its cardioprotective effect. But unopposed estrogen therapy also carries the risk of inducing endometrial cancer. A compelling body of evidence indicates that adjunctive progestogen protects effectively against estrogen-induced endometrial adenocarcinoma, and that progestogen therapy is effective in the treatment of hyperplasia in most women who have taken unopposed estrogen. Yet there is concern that adjunctive progestogen may attenuate the cardioprotective effects of estrogen. It is therefore agreed that adjunctive progestogen therapy is not indicated for hysterectomized women, and should be given at the lowest effective dose to non-hysterectomized women. Phase II dose-ranging clinical trials using secretory transformation as an efficacy endpoint to estimate protective effects of different doses of progestogen against endometrial hyperplasia/adenocarcinoma are complicated by the possibility that the doses protecting against hyperplasia may differ from those producing secretory changes. Further work is needed to identify one or several progestogen-regulated markers that most closely correlate with protection against estrogen-induced endometrial cancer.

Atrophy↗
PubMed1992

Effects of transforming growth factors and regulation of their mRNA levels in two human endometrial adenocarcinoma cell lines.

The effects of the transforming growth factor-beta 1 (TGF-beta 1) and epidermal growth factor (EGF) on the growth of cells from 2 endometrial cancer lines, Ishikawa and HEC-50 were evaluated by measuring rates of DNA synthesis and changes in cell numbers during culture. EGF at 17 and 1.7 nM concentrations consistently enhanced HEC-50 cell proliferation. TGF-beta 1 inhibited Ishikawa cell proliferation but, unexpectedly for epithelium-derived cells, stimulated HEC-50 cell growth. This effect is of interest as it indicates that endometrial cells can acquire an altered responsiveness to a growth inhibitor during the process of malignant transformation. Northern blot analyses showed expression of TGF-alpha, TGF-beta 1 and EGF receptors mRNA in both cell lines. Neither estradiol (E2) nor 4-hydroxytamoxifen (OHTam) affected mRNA levels for either TGF-alpha or TGF-beta in HEC-50 cells, a line unresponsive to E2 for proliferation. In Ishikawa cells, previously shown to respond to both E2 and OHTam by increasing proliferation rates, E2 increased TGF-alpha mRNA and reduced TGF-beta mRNA levels. OHTam lowered the levels of both mRNA species, although the effect was greater on TGF-beta than TGF-alpha mRNA. These data are consistent with, but do not prove, the existence of a possible autocrine regulation by TGF-alpha and TGF-beta of human cancer cell proliferation, which might be under E2 influence in Ishikawa cells.

Adenocarcinoma↗
PubMed1992

Growth-promoting effects of progesterone in a human endometrial cancer cell line (Ishikawa-Var I).

Significant growth responses to progesterone of human endometrial adenocarcinoma cells (Ishikawa-Var I) were observed under in vitro culture conditions. Progesterone affected both the rate of exponential proliferation and cell population densities after the exponential phase. In the presence of the hormone, the doubling time of exponentially proliferating cells was reduced from 44 to 35.6 h and cell densities were increased by as much as 2-3 times over those of controls during approx. 2 weeks in culture. The effects of progesterone on cell population growth were dose dependent. Estradiol (10(-8) M) and testosterone (10(-6) M) did not affect cell densities and the effects of dexamethasone (10(-6) M) were small. In contrast, both progesterone and estradiol stimulated colony formation under anchorage-independent conditions in soft agar. These results suggest the possibility that growth of sensitive cell clones in endometrial tumors could be enhanced in some patients during adjuvant progestin therapy.

Adenocarcinoma↗
PubMed1991

Transforming growth factor gene expression in human endometrial adenocarcinoma cells: regulation by progestins.

In an attempt to understand the antiproliferative effects of progestins in endometrial cancer, we have examined the effects of the potent progestin, medroxyprogesterone acetate (MPA), on the cell proliferation and the expression of transforming growth factor (TGF) alpha and beta genes in human endometrial adenocarcinoma cell lines. The two cell lines used were Ishikawa, var 1, and HEC-50. In addition, the effects of exogenous TGF-alpha and anti-epidermal growth factor (EGF) receptor monoclonal antibody on cell proliferation were determined. Incubation of both cell lines with MPA resulted in a time- and dose-dependent inhibition of cell proliferation. Half-maximal growth inhibition was observed at 0.6 nM. In Ishikawa cells, the relative abundance of TGF-alpha was significantly reduced by MPA. A significant decrease in TGF-alpha mRNA was apparent 6 h after exposure to MPA and a further decrease was seen 12-24 h after addition of the progestin. The concentration of TGF-alpha immunoreactivity in conditioned medium of MPA-treated cells was also significantly reduced compared to control cultures. MPA had no effect on TGF-alpha expression by HEC-50 cells. EGF mRNA was not detected by Northern blot analysis in either cell type. MPA had no significant effect on EGF receptor mRNA abundance but resulted in a small increase in EGF receptor number in Ishikawa cells. Anti-EGF receptor monoclonal antibody (0.6-6 nM) inhibited Ishikawa cell growth but had no effect on HEC-50 cell proliferation. Exogenous TGF-alpha stimulated proliferation of both cell lines, but Ishikawa cells were significantly more sensitive to exogenous TGF-alpha than HEC-50 cells. Furthermore, TGF-alpha could reverse the growth inhibitory effects of MPA on Ishikawa cells. A decrease in TGF-beta mRNA abundance was also observed in MPA-treated Ishikawa and HEC-50 cells. This effect was of small magnitude, variable, and only observed after prolonged exposure to MPA. These observations are consistent with the hypothesis that the antiproliferative effects of progestins on Ishikawa cells are mediated by decreased expression and autocrine action of TGF-alpha. Since similar growth inhibition is also seen in the HEC-50 cells in which progestins have no effect on TGF-alpha expression, additional mechanisms are likely to be involved in the antiproliferative effects of progestins in human endometrial cancer.

Antineoplastic Agents↗
PubMed1989

Proliferation and responsiveness to estrogen of human endometrial cancer cells under serum-free culture conditions.

Studies of hormonal growth regulation in cultured human endometrial cancer cells are limited by the requirement of exogenous growth factors, usually supplied by addition of serum. The present report provides evidence that estradiol can stimulate proliferation of endometrial cancer cells of the Ishikawa line in the absence of serum or added growth factors. Mitogenic effects of estrogen were demonstrated in two different experimental systems, in cells attached to the substratum of mammalian tissue culture dishes, and in cells forming colonies in soft agar under anchorage-independent conditions. Addition of estradiol to a mixture of serum-free, phenol red-free Dulbecco's minimal essential medium and Ham's F-12 medium, supplemented with L-glutamine and 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid [basal medium: (BM)] significantly increased the proliferation of cells attached to culture dishes. Dose-response experiments revealed maximal estradiol stimulation at 10 nM; significant responses were also observed at 1 nM and at 100 nM concentrations. The mitogenic effect of 10 nM estradiol was comparable to that of 1% charcoal-treated fetal bovine serum and the two effects were additive. The presence of estradiol in serum-free BM resulted in a shortening of the doubling time of exponentially proliferating cells from 38 to 29 h. From the labeling index, measured after exposure to a pulse of [3H]thymidine, and from the mitotic index, both determined in exponentially proliferating cells, the lengths of the S and M phases were calculated to be 11 and 1 h, respectively. From these data it was estimated that estradiol shortened the G1 phase by approximately 40%, from 22 to 13 h. Estradiol doubled the colony formation efficiency of cells plated in BM containing 0.3% agar in the absence of serum as well as in the presence of 1% charcoal-treated fetal bovine serum. The stimulation of colony formation by estradiol was influenced by medium components, since no effects were observed in minimal essential medium. The colony formation efficiency was positively related to the serum concentrations and remained significantly lower in minimal essential medium than in BM at comparable serum levels. The observed positive relationship between colony formation efficiency and cell densities at plating suggests a cooperative mitogenic effect, likely due to autocrine and paracrine action of secreted growth factors. These results define a model to evaluate hormonal growth regulation mediated by autocrine mitogens in human endometrial cancer cells in the absence of interfering exogenous growth factors.(ABSTRACT TRUNCATED AT 400 WORDS)

Cell Aggregation↗
PubMed1989

Stimulatory effects of 4-hydroxytamoxifen on proliferation of human endometrial adenocarcinoma cells (Ishikawa line).

The effects of trans-4-hydroxytamoxifen (OHTam) on proliferation of cells of the Ishikawa human endometrial adenocarcinoma line were studied under serum-free, phenol red-free conditions and compared to those of estradiol. The addition of OHTam (1 microM) to basal medium (BM), consisting of equal parts of Dulbecco's modified Eagle's medium and Ham's F-12 with additional glutamine and 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, resulted in significant increases in cell numbers relative to controls. These effects were even greater than those obtained with estradiol (10 nM-1 microM) or 1% charcoal-treated fetal bovine serum (ctFBS). Addition of 1% ctFBS to BM containing 1 microM OHTam further increased cell numbers whereas addition of estradiol (10 nM) did not do so. The stimulation of growth was positively correlated with OHTam concentrations in the range of 10 nM to 1 microM. Dissociation of estradiol and OHTam proliferative effects was observed in a variant of Ishikawa cells in which estradiol did not increase proliferation while OHTam had a strong stimulatory effect. The growth-promoting effects of OHTam were also observed in BM containing 5% or 15% ctFBS. In contrast, in parallel experiments in which BM was replaced by minimal essential medium (Eagle's) with Earle's salts, OHTam (1 microM) did not stimulate proliferation under these conditions and acted as an antiestrogen, inhibiting the proliferative effects of estradiol. These results illustrate marked effects of medium composition on proliferation and antiestrogenic actions of OHTam. Alkaline phosphatase activity was strongly stimulated by estradiol (10 nM) but only very weakly affected by OHTam (1 microM); at these concentrations, OHTam inhibited the effect of estradiol, both in serum-free BM and in minimal essential medium plus 15% ctFBS, demonstrating dissociation in its actions on proliferation and on enzymatic activity. These findings suggest that OHTam may stimulate the proliferation of particular clones of endometrial cancer cells in human tumors. They also suggest that OHTam can exert effects not mediated by the estrogen receptor system, or form OHTam-estrogen receptor agonistic complexes unlike those resulting from estradiol-estrogen receptor interactions. Clearly, Ishikawa cells provide a useful model to investigate mechanisms of action of antiestrogens.

Adenocarcinoma↗
PubMed1989

Effects of serine and glycine on proliferation of an Ishikawa cell variant.

The proliferation of cells on an Ishikawa human endometrial adenocarcinoma line variant (Ishikawa-Var I) is markedly influenced by the medium used to culture them, viz. MEM vs BM (basal medium; DMEM/Ham's F12, 1/1, with additional glutamine and HETES), under serum-free conditions. Components of BM which are not present in MEM were systematically tested in order to identify those that might account for these differences. Cells were cultured for various periods of time, up to 8 days, in serum-free MEM to which the components to be tested were added. Cell population densities were evaluated using a fluorometric DNA assay when the cells were grown in multiwell plates, or by cell counting when the cells were cultured in plastic dishes. It was found that addition to MEM of a mixture of the amino acids that this medium lacks, significantly increased cell density. By testing individual amino acids at the concentrations present in BM, it could be demonstrated that addition of serine alone was sufficient to obtain the densities achieved with BM. Glycine, a metabolic precursor of serine, had a similar but smaller effect. None of the other missing compounds of BM was effective. Effects of serine on DNA synthesis were also estimated by measuring incorporation of [3H]thymidine for 1 h after a 24 h culture period in MEM. The effect of serine was similar and additive to that of 1% charcoal-treated fetal bovine serum. A serine concentration dependence studied either with this method or measuring DNA/well after 8 days in culture showed detectable effects at 0.005 mM concentration and maximal responses at about 0.025 mM. These findings are of potential importance in studies on regulatory mechanisms of cell proliferation. A possibility to be explored, for instance, is that serine added to the medium increases intracellular phosphatidylserine concentrations leading to increases in the activity of protein kinase C, a stimulator of cell proliferation in some systems.

Adenocarcinoma↗
PubMed1989

[Mechanism of action of endocrine therapy of endometrial carcinoma].

The mechanism of action of sex steroid hormones on endometrial carcinoma was analyzed by a cell culture system. 1) Estrogenic actions such as enhancement of ALP activity, PR level and cellular growth were confirmed in Ishikawa endometrial carcinoma cells which possess ER. 2) ER and PR are both localized immunocytochemically in the nuclei of Ishikawa cells, confirming the correctness of Gorsky and Greene's theory in endometrial carcinoma. 3) In Ishikawa cells with PR, progestins stimulated E2DH activity and glycogen synthesis and reduced ER level, thus proving the existence of their hormonal action. We cannot, however, rule out the pharmaceutical action of progestin, because a decrease in nucleic acid syntheses and ALP activity, alteration in electron microscopic observation and finally cellular death were observed in endometrial cancer cells without PR. 4) Conversely, Tamoxifen, anti-estrogen, stimulated the cellular growth in serum-free environment of culture. We must therefore be careful in using it clinically.

Adenocarcinoma↗
PubMed1988

Growth and hormonal responsiveness of human endometrial stromal cells in culture.

The present review describes and discusses published results on growth and hormonal responsiveness of human endometrial stromal cells in culture. The proliferative potential of serially subcultured cells, that is, the number of cell doublings before cells enter mitotic senescence and cease to divide, was unusually high in stromal cells from several endometrial specimens, a property that may reflect the unique proliferative capacity of human endometrium when compared to other adult tissues. Fluorescent visualization of microfilaments revealed distinct age-related changes in the distribution of cytoskeletal fibers. Addition of ovarian steroids to the culture medium of stromal cells resulted in significant morphologic changes. From comparative studies using different culture media it became evident that medium components remarkably influenced cell morphology during early culture periods in an irreversible manner. Cultured stromal cells yielded interesting results in experiments designed to define the role of polyamines in growth regulation. Proliferation was greatly inhibited when polyamine levels were reduced by specific inhibition of ornithine decarboxylase, the first and rate limiting enzyme in polyamine synthesis which produces putrescine by catalytic conversion from ornithine. The antiproliferative effects were reversed by addition of putrescine to the culture medium. These results clearly establish a causal link between polyamine depletion and growth deficiencies and reveal an essential function of polyamines in stromal cell proliferation. Hormonally regulated parameters in cultured stromal cells include aromatase activity, pregnancy-associated plasma protein-A, 51K secreted protein, prolactin and laminin. The hormonally regulated production of prolactin and laminin, both considered markers of decidualization, together with morphologic changes of stromal cells to decidual-like cells, strongly suggest that human endometrial stromal cells, when subjected to appropriate hormonal stimulation, are capable of differentiating into decidual cells in culture. Cultured stromal cells therefore offer a unique opportunity to examine the complex changes in gene expression associated with decidualization. In addition, in vitro decidualization may prove to be an effective diagnostic tool in certain cases of infertility. Finally, decidualization of cultured stromal cells represents a relevant end point for testing compounds of potential clinical importance, such as synthetic progestins or antifertility drugs.

Age Factors↗
PubMed1987

Estradiol metabolism in Ishikawa endometrial cancer cells.

Estrogen-responsive human cells derived from a specimen of well differentiated endometrial adenocarcinoma (Ishikawa line) were incubated with [3H]estradiol (E2) at various concentrations and the medium was sampled at 3, 6 and 24 h to evaluate the kinetics of removal of the hormone and the formation of unconjugated or sulfated metabolites. The detectable products of metabolism were estrone and the conjugate estradiol-3-sulfate. The latter was identified by high pressure chromatography, before and after acetylation, oxidation, and hydrolysis. The disappearance of [3H]E2 from the medium was found to follow first order kinetics between 3 and 24 h, with half-lives increasing from 4.7 to 53 h as the initial concentrations of the hormone were raised from 10(-8) to 10(-6)M. At the lowest concentration, practically all of the [3H]E2 added to the cultures was converted to estradiol-3-sulfate in 24 h, whereas at 10(-6)M oxidation to estrone was quantitatively more important than sulfation. These results indicate the presence in Ishikawa cells of an estrogen sulfotransferase of low Michaelis constant for E2, and 17 beta-oxidoreductase activity that significantly contributes to the metabolism of E2 only at higher concentrations of substrate.

Adenocarcinoma↗
PubMed1987

Proliferative potential and polymorphism of human endometrial stromal cells.

The proliferative potential of stromal cells from human endometrium, separated from glands by dispersion in the presence of collagenase and subsequent passage through a sieve, was evaluated by determining the total number of cell doublings achieved when cells were repeatedly subcultured in a 1:2 split ratio in Ham's F-10 medium containing 10% fetal bovine serum (FBS). Fifty doublings or more (up to 100) were observed in 8 of the 26 specimens (30%) which we examined. This number of doublings is high for cells obtained from adult tissues and may in part reflect the unusually great proliferative capacity of human endometrium when compared to that of other tissues. The shape of the stromal cells depended on the medium in which they were originally cultured. Cells cultured in Ham's F-10 medium containing 10% FBS showed the typical fibroblastic morphology at confluence; they appeared elongated or spindle-shaped and formed monolayers. In contrast, cultures in CMRL-1066 medium in the presence of 10% FBS appeared polygonal or stellate-shaped and also formed monolayers. In about 50% of the cultures in CMRL-1066 medium we observed fibroblast-shaped cells that superficially resembled cells grown in Ham's F-10 medium, but were able to form dome structures. In some cultures the regions of prominent overgrowth were macroscopically visible. Switching media during later passages did not reverse the shape of the cells obtained in CMRL-1066 medium or that of the fibroblast-shaped cells in Ham's F-10 medium, suggesting either that the growth of a subpopulation was favoured early during cellular adaptation to primary culture or that there was a single cell population whose phenotype was determined early in culture and then no longer responded to medium factors. Examination of the cytoskeleton after visualization with rhodamine-labelled phalloidin revealed that the arrangement of the microfilaments corresponded to the cell shape observed in living cells under the phase contrast microscope. Distinct changes in morphology were observed when primary stromal cell cultures in CMRL-1066 medium were exposed to progesterone, indicating that progestins may affect cytoskeletal proteins.

Actin Cytoskeleton↗
PubMed1987

Endometrial carcinoma: two diseases?

Ninety-five patients diagnosed as having stage I endometrial carcinoma (EC) were divided into two groups, one with associated adenomatous hyperplasia (AH; group 1) and the other without (group 2). Adenomatous hyperplasia results from estrogenic stimulation of the endometrium. Therefore, patients in group 1 are considered to have an estrogen-related EC. Group 1 included 49 patients with an average age of 59; group 2 included 46 patients with an average age of 65. Review of the histologic characteristics of EC showed that group 1 tumors are better differentiated and less invasive and that their morphology is closer to the normal glandular structure of the endometrium. Group 2 tumors are less well differentiated, more often invade the myometrium, and include histologic variants such as papillary, clear cell, and anaplastic carcinoma that are dissimilar from the glandular structure of the normal endometrium. Mucinous adenocarcinomas and the presence of stromal foam cells were found to be associated with group 1 EC. Progesterone receptors (PR) were measured in a sample of 30 patients. They were present in all cases of group 1 ranging from 50 to 2,400 fmol/mg protein and absent or very low (30-190 fmol/mg protein) in group 2. All EC with stromal foam cells had high PR (380-2,400 fmol/mg protein). This study confirms that estrogen-related EC is generally a better differentiated and less aggressive tumor and suggests that there are two types of EC. The tumors not related to estrogens, which are histologically more malignant, were seen in an older age group of patients. In addition to the currently accepted methods of clinical evaluation of EC patients, defining the morphologic and biochemical characteristics of two types of EC may contribute to the management of EC, now the most prevalent cancer of the female pelvis. The patients known to be at risk for endometrial carcinoma, identifiable by abnormal hormonal manifestations (obesity, infertility, and other conditions related to hyperestrogenism) as well as those receiving exogenous estrogens are likely to develop a better differentiated and less aggressive form of neoplasia. It would be important to elaborate a system of early detection of EC in the group of elderly patients with no signs of hyperestrogenism prone to develop the less differentiated and biologically more aggressive tumors.

Adenoma↗