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G Dallenbach-Hellweg

Publications and source records attributed to G Dallenbach-Hellweg.

At least 19 recordsLinked to original sources
PubMed1997

Changes in the endometrium caused by endogenous hormonal dysfunction.

The endometrium responds precisely and predictably to every hormonal dysfunction that may result from absent, deficient or excessive hormone production caused by an arrest of follicular maturation at different stages. Anovulatory failures may be due to arrest of follicular development and may cause endometrial atrophy or deficient proliferation. Arrest of follicular regression may result in irregular proliferation or various degrees of hyperplasia. Ovulatory failures may be due to arrest of corpus luteum maturation and followed by deficient secretion with dissociated or coordinated delay in differentiation. Arrest of corpus luteum regression may cause secretory hypertrophy. Both, anovulatory and ovulatory functional disturbances, are followed by prolonged and irregular endometrial shedding with necrosis, since regular dissociation of endometrial stromal cells is impaired. Almost all such functional deviations may cause infertility.

Adenoma↗
PubMed1997

Histopathology of functional and neoplastic changes in cervix and endometrium.

Over 90% of all cervical carcinomas originate from hyperplastic reserve cells of the endocervix. When cell cycles of the pluripotent reserve cells are shortened or damaged by hormonal overstimulation or toxic chemicals, DNA repair after viral infection is no longer possible. The immortalized cells may then become malignant with precancerous and carcinomatous differentiation to squamous, adenosquamous or adenocarcinomas. To determine the type of HPV infection is clinically important for estimating prognosis and for planning further therapy. In recent years HPV 18-associated endocervical adenocarcinomas have increased considerably in number as compared with squamous cell carcinomas. In endometrial carcinomas the estrogen-stimulated endometrioid types must be distinguished from the gestagen-stimulated mucinous, clear-cell and serous-papillary types because prognosis as well as operative and adjuvant therapy differ considerably. The endometrioid carcinomas and their preceeding atypical hyperplasia are frequently associated with bcl-2, c-myk and c-ki-ras oncogenes. The mixed Muellerian types, in contrast, and their preceeding mucinous, clear-cell and serous-papillary metaplasias very often show genetic defects, LOH, mutations, amplifications and deletions, especially of p53. The endometrial carcinomas occurring in the reproductive age period are of endometrioid type and frequently present microsatellite instabilities. In rapidly proliferating tissues like the endometrium there appears to be a close correlation between functional and neoplastic changes. A simple explanation for that might be found in the greatly enhanced mitotic activity in a hormonally stimulated endometrium with shortening of cell cycles, leaving insufficient time for DNA repair. Since, however, carcinogenesis is a multi-factorial event, to correlate endometrial function with morphology can contribute only one aspect to the understanding of neoplastic change. In discussing hormonal function it is important to realize that the endocervix and the endometrium differ not only in their cellular structure, but they react antagonistically to hormonal stimulation: excessive (endogenous or exogenous) estrogen results in hyperproliferation of endometrial epithelial cells, but in the cervix in differentiation of the endocervical cells with mucus production. Extensive synthetic gestagens lead to hyperproliferation of endocervical epithelial cells (reserve cells as well as glandular epithelial cells), but in the endometrium cause atrophy (see Table 1).

Cell Transformation, Neoplastic↗
PubMed1996

Lower frequency of allele loss on chromosome 18q in human breast cancer than in colorectal tumors.

Inactivation of tumor suppressor genes is thought to be a critical step in tumorigenesis. The DCC (deleted in colorectal carcinoma) gene, located on the long arm of chromosome 18, has been shown to be frequently deleted in colorectal tumors. To investigate the involvement of allelic deletions on chromosome 18q in breast cancer tumorigenesis we analyzed 28 primary breast tumors and 28 colorectal tumors (24 carcinomas, 4 adenomas) with four different polymorphic DNA markers detecting RFLPs on chromosome 18q. In breast cancer we found loss of heterozygosity (LOH) in 4 of 27 (15%) informative cases whereas 15 of 25 (60%) colorectal tumors showed allelic deletions. In all cases of allelic loss the DCC locus or its proximal vicinity (locus SSAV1) were involved. LOH on chromosome 18q occurs both in breast and colorectal cancer, yet the frequency of these deletions in breast tumors is lower than in colorectal tumors. Moreover, in breast cancer these mutations were only detected in large and undifferentiated tumors.

Adult↗
PubMed1996

[Morphologic endometrium changes with tamoxifen].

Women receiving tamoxifen as adjuvant therapy for breast cancer usually develop atrophy of the endometrium. Cystic polyps as well as endocervical and clear-cell metaplasias also frequently arise in the these atrophic endometria. The invasive endometrial carcinomas we have observed in these women have all been until now either mucinous, clear-cell or serous-papillary carcinomas, that is, different from the endometrioid type of adenocarcinomas that arise under estrogenic stimulation. Our histological studies support the assumption that tamoxifen has an antiestrogenic, gestagen-like action on the endometrium; they contradict the premise that tamoxifen therapy exerts an estrogen effect.

Antineoplastic Agents, Hormonal↗
PubMed1995

Mucinous and clear cell adenocarcinomas of the endometrium in patients receiving antiestrogens (tamoxifen) and gestagens.

In recent years, tamoxifen therapy for breast carcinoma has been associated with endometrial carcinoma with increasing frequency. We describe 10 cases of this association as well as 12 cases of endometrial carcinoma after therapy with synthetic gestagens. All but one of the 22 carcinomas we describe here were of the mucinous or clear cell type, and arose in atrophic endometria containing foci of mucinous (endocervical) and clear cell metaplasia. In the endometrium, the antiestrogenic action of tamoxifen closely resembles the antiproliferative action of synthetic gestagens on the endometrium. In the endocervix, tamoxifen as well as synthetic gestagens, stimulate the endocervical mucosa to proliferate. In the endometrium, both tend to produce mucinous (endocervical) and clear cell metaplasia. A weak estrogenic action of tamoxifen may be expected to augment its own antiestrogenic gestagen-like action. Consequently, the antiestrogenic effect of tamoxifen is most likely responsible for the development of endocervical metaplasia and possibly corresponding endocervical and clear cell types of carcinomas within an atrophic endometrium. We believe that gestagen therapy administered to patients with endometrioid type carcinoma is contraindicated in patients with mucinous adenocarcinoma of the endometrium and that this is another reason to distinguish between these two types of carcinoma.

Adenocarcinoma, Clear Cell↗
PubMed1991

Immunohistochemical studies on uterine tumors. I. Invasive squamous cell carcinomas of the cervix and their precursors.

40 invasive carcinomas and 80 preinvasive lesions of the uterine cervix were studied immunohistochemically; 40 benign lesions served as controls. On histological and immunohistochemical examination, invasive and preinvasive carcinomas were subdivided in the squamous (large cell, ectocervical) type and the reserve cell (small, large or clear cell, endocervical) type. Immunohistochemically, 100% of the invasive and preinvasive squamous cell carcinomas were positive with anticytokeratins 13, 14, 16 and negative with anticytokeratin 8 and anti-CEA. Most of the invasive and preinvasive reserve cell carcinomas showed a coexpression of cytokeratins 13, 14, 16, 8 and CEA. The subdivision of invasive carcinomas of the ecto- and endocervix into squamous cell and reserve cell types made by means of their structural differences is substantiated and re-evaluated by their immunohistochemical reactions. Both types of carcinomas retain the complex pattern of cytokeratins shown by their cells of origin. The reserve cell carcinomas, in addition, acquire a coexpression for CEA that indicates malignant transformation. The subdivision is of clinical importance because both types of carcinomas vary in their mode and speed of invasion and spread and in their association with HPV infection.

Carcinoembryonic Antigen↗
PubMed1991

[Receptivity of the endometrium: comparison of ultrasound and histologic findings after hormonal stimulation].

On the day of the scheduled embryo transfer, endometrial biopsies were taken from 53 patients of an IVF-programme. There was subsequent failure of fertilisation in all of these patients. The histologic pattern, compared with reflectivity and thickness of the endometrium was determined sonographically on the same day. All patients had been stimulated with hMG/hCG, and the ovaries and the endometrium had been monitored by transvaginal sonography. The reflectivity pattern was divided into grades (A to D according to Smith et al., 1984) and related to histological findings. The distribution of the grades was as follows: 16 patients (30%) grade A, 22 patients (42%) grade B, and 15 patients (28%) grade C. There was no case of grade D in our study. The results of histologic examination for grades A to C were not significantly different from each other. However, in only 37% of grade A, 63% of grade B and 66% of grade C, the endometrial response corresponded to the state of the cycle. Endometrial thickness for the receptive and non-receptive groups was not significantly different (8.8 +/- 0.29 mm vs. 9.13 +/- 0.4 mm). The results show no correlation between histologic findings and endometrial thickness or reflectivity. We therefore conclude, that sonographic determination of these parameters is not helpful in the evaluation of the degree of endometrial response.

Chorionic Gonadotropin↗
PubMed1991

The value of immunohistochemistry in the differential diagnosis of endometrial carcinomas.

Endometrial carcinomas may originate from endometrial glandular epithelium and show endometrial differentiation, or from various types of metaplasias developing in the endometrium from pluripotent Müllerian epithelium. They then show endocervical or serous papillary differentiation. Because of their differences in spread, speed of growth and survival rates, it is important to subclassify these endometrial carcinomas. Immunohistochemically, adenocarcinoma with endometrial differentiation including adenoacanthomas and adenosquamous carcinomas can be recognized by their coexpression of cytokeratin 8 and vimentin, and by their negative reaction for CEA. Distinction from adenocarcinomas with mucinous differentiation, including mucoepidermoid adenocarcinomas, is possible by their negative reaction for vimentin and by their positive reaction for CEA. On the other hand, carcinomas with mucinous differentiation primarily located in the endometrium can not be distinguished from those primarily located in the endocervix by immunohistochemistry; that distinction must be made topographically. The same holds true for clear cell carcinomas of both locations. Over the past decade, mucinous adenocarcinomas and clear cell carcinomas originating from the endometrium have increased, whereas adenocarcinomas with endometrial differentiation have become less frequent. This shift is closely related to the altered postmenopausal hormone substitution with the addition of the synthetic gestagens. These apparently stimulate proliferation of endocervical epithelium not only in the endocervix, but also that arising in endocervical metaplasias of the endometrium.

Adenocarcinoma↗
PubMed1991

[New cytogenetic classification of precancerous lesions and carcinomas of the endometrium: possibilities and limits of immunohistochemical differentiation].

Various grades of adenomatous hyperplasia represent precancerous states leading to the most common type of adenocarcinoma with endometrial differentiation. Grades 1 and 2 are characterized by architectural abnormalities only (complex hyperplasia). They rarely progress to carcinoma. Grade 3 in addition is characterized by cytological atypicalities (atypical hyperplasia) and shows a much higher progression rate into invasive carcinoma. Endometrial carcinomas may originate from endometrial glandular epithelium and show endometrial differentiation, or from various types of metaplasias developing in the endometrium from pluripotent Müllerian epithelium. They then show endocervical or serous papillary differentiation. Because of their differences in spread, speed of growth and survival rates, it is important to subclassify these endometrial carcinomas. Immunohistochemically, adenocarcinomas with endometrial differentiation including adenoacanthomas and adenosquamous carcinomas can be recognized by their coexpression of cytokeratin 8 and vimentin, and by their negative reaction for CEA. Distinction from adenocarcinomas with mucinous differentiation, including muceopidermoid adenocarcinomas, is possible by their negative reaction for vimentin and by their positive reaction for CEA. On the other hand, carcinomas with mucinous differentiation primarily located in the endometrium can not be distinguished from those primarily located in the endocervix by immunohistochemistry; that distinction must be made topographically. The same holds true for clear cell carcinomas of both locations. Over the past decade, mucinous adenocarcinomas and clear cell carcinomas originating from the endometrium have increased, whereas adenocarcinomas with endometrial differentiation have become less frequent. This shift is closely related to the altered postmenopausal hormone substitution with the addition of the synthetic gestagens. These apparently stimulate proliferation of endocervical epithelium not only in the endocervix, but also that arising in endocervical metaplasias of the endometrium.

Adenocarcinoma↗
PubMed1991

[Role of steroid hormones and related biological substances in the etiology of endometrial carcinomas].

Synthetical oestrogens, as well as gestagens may cause metaplastic changes of the endometrial epithelia. While squamous and tubal metaplasia are most often due to oestrogenic stimulation and develop in hyperplastic endometria, mucinous and clear cell metaplasia are stimulated by gestagens and tamoxifen. Tamoxifen seems to act gestagen-like on the endometrium. We present data of 31 patients, who were treated with tamoxifen for breast cancer disease. 3 of these 31 developed endometrial adenocarcinoma.

Adenocarcinoma↗
PubMed1990

The histogenetic origin of cervical mesonephric hyperplasia and mesonephric adenocarcinoma of the uterine cervix studied with immunohistochemical methods.

Forty-four cases of mesonephric hyperplasia (MH) and two adenocarcinomas arising from mesonephric remnants (MA) in the cervix were compared immunohistochemically with 10 embryonic and fetal mesonephric tissues. The mesonephric cells retained their pattern for intermediate filaments during ontogenesis, as well as in the mature, hyperplastic, and neoplastic states: they expressed cytokeratin 8, cytokeratin 13, and vimentin, the two latter in variable amounts. In embryonic mesonephric tissues, cytokeratin was absent, whereas the staining for vimentin was intense. Fetal mesonephric cells stained for cytokeratin 13 and vimentin, but that staining diminished as maturation progressed. All MH and MA expressed cytokeratin 8, whereas only 20-30% of the cells in MH and 10-20% of carcinomatous mesonephric cells showed positive reactions with anti-cytokeratin 13 and anti-vimentin. CEA was always negative in cells of mesonephric origin. We regard these results to be important, since the reactions with anti-CEA and anti-vimentin enable one to distinguish cervical adenocarcinomas of mesonephric origin from those of endocervical origin, the latter being CEA-positive and vimentin-negative. Clinical studies revealed that approximately 75% of the patients with MH had used oral contraceptives for several years, 46% had precancerous lesions of the cervix, and in 62% the cervical mucosa showed adenomatous microglandular hyperplasia. We believe that hyperplasia of mesonephric remnants in the cervix may occur more often in patients with disturbed hormonal balance. However, the lack of a control population does not enable us to advance this hypothesis with assurance.

Adult↗
PubMed1989

[Disseminated peritoneal leiomyomatosis. A rare disease picture].

After taking oral contraceptive hormones continuously for 17 years, a 44 year old patient developed enlarging uterine leiomyomas and multiple small to tiny subperitoneal nodules throughout the pelvic peritoneum. Histologically and immunohistochemically, the nodules proved to be leiomyomas. Similar nodules were induced in young female guinea pigs by injecting them with estradiol twice weekly. The first nodules appeared after four months. Approximately 50 cases of Leiomyomatosis peritonealis disseminata (LPD) have been reported to date in the world literature. Of these, 23 patients were pregnant. Seventeen had taken oral contraceptives continuously for many years (from 8-17). The developing leiomyomatous nodules probably arise from the Müllerian epithelium, which is distributed throughout the subperitoneal mesenchyme. By appropriate individual predisposition and excessive hormonal stimulation, the Müllerian derivatives proliferate along lines of myofibrous differentiation. Since the oral contraceptives all contained in addition to estradiol the synthetic gestagen norethindrone (or lynestrenol) and since these same hormones led to identical tumor nodules in animal experiments, it seems to suggest, that the stimulation of the Müllerian epithelium results from a specific combination of hormones. A similar combination of hormones may develop endogenously during a hormonally disturbed pregnancy. To prove these assumptions, larger case and interdisciplinary studies are needed. It is of clinical importance to realize, that the dormant Müllerian epithelium may be stimulated by excessive hormones to proliferate and that the proliferations produced, such as the benign nodular tumors of LPD, must be differentiated from nodular metastases of malignant tumors.

Adult↗
PubMed1989

[Immunohistochemical receptor findings in the endometrium and therapeutic consequences in endogenous and exogenous functional disorders and cancer].

We studied immunohistochemically cryostat sections made from fresh endometrial tissue, immediately frozen after removal (86 hysterectomy specimens, 6 curettages) for their content of oestrogen receptors (ER) using the ER-ICA assay. Routine histological sections were prepared from parallel specimens of the endometria for determining endometrial functions. The evaluation of the immunohistiological preparations showed that the ER content in the endometrium was closely related to the endogenous hormone stimulation. A further refinement and differentiation of that relationship became possible and correlated well with the various forms of follicle and corpus-luteum insufficiencies. The results indicated that it is now possible to recommend therapy of functional disorders of the endometrium, esp. in sterility cases, without need or knowledge of serum hormone levels. As the endometrial glandular proliferation increases, the density of the ER becomes more intense. In contrast, under therapy with predominantly gestagenic preparations or after these are discontinued, the ER are decreased more than found in normal glands at that degree of proliferation. Whereas the atrophic endometria of old age contained greatly diminished but still detectable ER, no ER could be found in endometrial atrophy induced by oral contraceptives. Carcinomatous endometria revealed a heterogeneous distribution of ER. The better the tumour cells were differentiated, the greater was the density of the ER. By contrast, the carcinomas derived from metaplastic Müllerian epithelium contained few or no ER. This difference is of practical importance, since an adjuvant anti-oestrogen therapy seems of value only with ER-positive carcinomas. The immunohistochemical determination of ER is more exact than the biochemical determination, for each single cell can be evaluated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1988

In vitro fertilization: the degree of endometrial insufficiency varies with the type of ovarian stimulation.

Fifty-eight patients in an in vitro fertilization program who did not have embryo transfers had endometrial biopsies performed on the second day after ovulation. The patients had been stimulated with clomiphene citrate (CC) and human chorionic gonadotropin (hCG) (group I); with CC, human menopausal gonadotropin (hMG), and hCG (group II), or with hMG and hCG (group III). Only 17 patients (30%) showed a normal luteal phase histology. The remaining 41 patients (70%) showed variety of endometrial abnormalities. Patients stimulated with hMG and hCG (group III) had a normal luteal phase at a significantly higher rate (48% versus 16%). Women below the age of 35 had a significantly higher rate of normal luteal phase histology than women older than 35 years. The study establishes abnormal endometrial histology as a possible cause of the low pregnancy rate of in vitro fertilization. The degree of endometrial histologic abnormality varies considerably with the type of ovarian stimulation used.

Adult↗