[Immunohistochemical detection of nuclear estrogen receptors with monoclonal antibodies in different types of breast cancer].
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Biomedical subjects
Publications and source records attributed to H E Stegner.
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Ultrastructural analysis using electron microscopy was performed on 16 cases of preneoplastic lesions of the vulva. They included specimens from patients with condylomatous dysplasia, carcinoma in situ, melanoma in situ and extramammary Paget's disease. Each showed significant differences from normal in the ultrastructural details.
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Antisera to CEA were used for the immunohistochemical localization and quantification of this antigen in 120 Bouin-fixed, paraffin embedded mammary carcinomas. These results were compared to tumor type, grading, staging, biochemical receptor status, cytosolic CEA-levels of the same tumors, and preoperative plasma CEA-levels. Mammary carcinomas were usually characterized by a low percentage of CEA-positive tumor cells: 50.9% of the cases contained more than 5% CEA-positive tumor cells and were therefore defined as being CEA-histopositive in this study. A relation could be shown between CEA-histopositivity and the histologic tumor type. The majority of invasive lobular carcinomas, tubular, and cribriform carcinomas was CEA-negative (72%). Conversely, 70% of invasive ductal carcinomas were CEA-positive. There was a significantly higher percentage of CEA-histopositivity in grade III tumors than in grade I/II carcinomas. The results obtained by quantification of the immunohistochemical staining of CEA were positively correlated with the results obtained by cytosolic CEA-assay. The overall concordance between tissue and plasma determinations of CEA was found to be 57.1%. A positive trend could be found between CEA-positivity and staging. However, no correlation was observed between CEA-positivity and estrogen receptor status.
Ovarian tumours form a broad spectrum of histological types which reflect significant differences with regard to their biological behaviour and their responsiveness to radiological and cytostatical therapy. Precise subclassification is a precondition for selective therapy. A special subclass of tumours is represented by so-called borderline tumours which form a significant proportion of the overall group of epithelian ovarian neoplasms. Borderline tumours are histologically defined tumours which are neither fully benign nor overtly malignant. Though capable to metastasise they are of low malignant potential and favourable prognosis. In clinical statistics borderline tumours should be registered as a special entity. Within the ordinary group of malignant epithelial tumours histological grading has proven to be of prognostic significance. Amongst a great spectrum of useful cyto-histological criteria, nuclear polymorphism. The number of mitoses, and necrosis are the most important predictive factors.
The results of preliminary investigations into specific immunohistochemical detection of the estrogen receptor in breast cancer tissue by means of monoclonal antibodies are presented. Thirty-one tumor tissue samples stored in a tumor tissue bank for between 10 and 35 months were immunohistochemically studied. The comparison between the immunohistochemical result and the result of the biochemical estrogen receptor assay show a large measure of agreement (90%). The comparison of the results with regard to response to endocrine therapy in cases of metastatization shows that immunohistochemical detection furnishes at least as much information as the dextran-coated charcoal method.
116 cases of early ductal breast cancer diagnosed during 1971 to 1981 were analysed. In 65 cases no invasion was detectable. 37 cases showed an early stromal invasion and in 14 cases the invasion was questionable. A palpable mass was seen in 32% of the noninvasive and in 46% of the early invasive cases. The most important mammographic signs were grouped, suspicious microcalcifications (87%). Multicentricity occurred in 26% of the noninvasive and 43% of the early invasive cases. Two cases of the noninvasive and two of the early invasive group had axillary metastasis. Positive nodes were seldom in early ductal carcinoma (3%) compared to 42 invasive comedo-carcinomas (36% positive axillary nodes). In the follow-up five local recurrences were detected in the noninvasive group and one each in the other groups. In the noninvasive group 17% local recurrences occurred after breast conserving modalities compared to 4% in mastectomy patients. As no reliable data for the selection and the results of breast preserving modalities are available now, mastectomy and axillary dissection may be the safest therapy. Only in small intraductal breast cancer (under 25 mm) the breast may be conserved (wide excision, segmental resection, quadrantectomy), if complete excision is carefully controlled by mammography and histology and follow-up is guaranteed.
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The Thomsen-Friedenreich antigen (TF-antigen), known as a precursor of the MN-blood-group system, has been suggested as a tumor-associated antigen of breast adenocarcinoma. In order to evaluate the TF-antigen as a tool in the histochemical detection of micrometastases, cryostat sections of 25 breast biopsies and 30 regionary lymph nodes were investigated. The study used a sensitive method for the fluorescent staining of the determining terminal disaccharide sequence of asialoglycophorin A by application of peanut agglutinin (PNA) and fluoresceinisothiocyanate-labeled F(ab')2 fragments of monospecific anti-PNA from rabbits. PNA binding was observed in 91% of the sections of predominantly ductal mammary carcinomas. In normal tissues and hyperplastic lesions, staining patterns were markedly different from that of malignant breast cells, and were confined to secretory glycoproteins. Lymph nodes, with histologically confirmed metastases of mammary carcinomas, showed specific PNA binding in the cytoplasm of tumor cells in 75% of cases. Even single malignant cells were demonstrable, which were not recognized at first by routine light microscopy. Fluorescent staining of lymph nodes, which were tumor-free in repeated histologic examinations, was confined to clearly diagnosible histiocytes in 3 of 15 cases. A sensitive indirect immunofluorescent technique demonstrating PNA binding is proposed to be of considerable value for the detection of single metastatic adenocarcinoma cells of the human breast.
Peanut lectin (PNL) is known to bind beta-D-galactosyl-(1-3)-N-acetyl-D-galactosamine, which provides antigenic determination of the Thomsen-Friedenreich antigen ( TFAg ). The aim of this study was to analyse the expression of peanut lectin binding sites in mammary carcinomas and to correlate these with tumor type, histological grading, staging and biochemical receptor status. The series comprised 120 invasive mammary carcinomas and 14 cases with normal breast tissue or benign epithelial proliferations as controls. In controls mainly luminal or apical PNL-binding was discovered, however, in all except three carcinomas a cytoplasmatic localisation of TFAg with three major patterns was found: diffuse, granular-globular and vacuolar reactions. The quantitative-qualitative evaluation of the PNL-staining revealed a statistically significant correlation between globular-vacuolar PNL-reaction and tumor type with a higher percentage of this type of reaction in invasive lobular carcinomas as opposed to tubular and invasive ductal carcinomas. Furthermore a statistically significant relationship was disclosed between PNL- histopositivity and estrogen positive - progesterone positive cases. However, the findings of contradictory PNL-status and hormone-receptor status illustrates clearly the difficulty of predicting the biochemical receptor status. No correlation was found between PNL-histochemistry, histological grading, and pathological staging. The practical implications of PNL-histochemistry of mammary carcinomas are discussed.
The Diagnostic Validity of Enhanced Lactate Dehydrogenase Activity in the Vaginal Secretion for Early Diagnosis of Diseases of the Female Genitals and the Mamma in Need of Treatment. An impregnated hygiene tampon (Gynaegnost) was used, which by a colour reaction permits the determination of augmented activity of lactate dehydrogenase (LDH) in vaginal secretion. The diagnostic validity of the results of the findings by this method in the detection of diseases of the female genitals and the mamma needing treatment was examined in two clinical diagnostic studies. The first study including 486 patients chiefly suffering from manifest carcinoma was aimed at solving a deliberately limited question. In patients with carcinoma stages I to IV of the most important genital locations augmented LDH-activity (correct positive results) was found in about 90%. A second study comprised 1955 women entering into outpatient gynaecological services for preventive examination; the definition of this series was difficult. Three categories of diagnostic groups can be determined by the results of this study. In the first category with the most important subgroup "routine examination without specification of a pathological finding" less than 20% "false" positive test results by the indicator were observed. A second category with inflammatory diseases (colpitis, endometritis) showed positive results in about one-third of the examinations. The third category comprised a minor number of malignant tumors roughly with a percentage of positive results corresponding to that of the first study. Augmented LDH activity in vaginal secretion is a diagnostic criterion which detects not only cancer; it is similar to the test of occult blood in faeces.(ABSTRACT TRUNCATED AT 250 WORDS)
Steroidogenesis in a histologically and ultrastructurally clearly defined Sertoli-Leydig cell tumor ( androblastoma ) was studied by incubation of tumor slices with tritiated and unlabeled pregnenolone. Metabolites were isolated by thin-layer and gel-column chromatography and identified by gas chromatography associated with a radioactivity detector and/or by gas chromatography-mass spectrometry. Steroids were detected by mass chromatography as the trimethylsilyl- or tert-butyldimethylsilyl ethers. The following steroids were found: progesterone, 20 alpha-dihydroprogesterone, 17 alpha-hydroxypregnenolone, 5-pregnene-3 beta,20 alpha-diol, 4-androstene-3,17-dione, dehydroepiandrosterone, testosterone, androsterone, and etiocholanolone. The two latter C19-steroids were found to be the principal metabolites. Neither estradiol-17 beta nor estrone were detected. There was evidence from ultramicroscopic studies that in addition to typical Leydig cells, neoplastic stromal and sex cord cells are involved in androgen metabolism.
Within a period of 8 years 12 women patients were referred to the authors with histologically established lymph node metastases in the axilla without a primary tumour being identified despite careful examination. Subsequent follow-up showed that the only possible cause in these patients was a primarily occult carcinoma of the breast. This rare manifestation of a carcinoma of the breast is discussed on the basis of the case reports and the literature with particular regard to the diagnostic and therapeutic problem involved.
500 cases of carcinoma of the female breast were analysed in connection with the problem whether there is any involvement of the mamilla in this disease. The mamilla was found to be involved in 98 cases (19.6%), the incidence rate of this involved increasing with advancing age. A comparison of the types of carcinoma showed that the largest group (44%) was represented by the solid carcinomas. The percentage of carcinoma distribution was approximately the same as the share of mamilla involvement, with the exception of adenoid carcinoma. Only 12% of the mamillae were involved with a tumour diameter of less than 3 cm, whereas in the case of larger carcinomas the percentage was 30%. The distance between tumour and mamilla is also important. If the mamilla was affected, the homolateral axilla was also affected in 54% of the cases, but this figure dropped to 27% if the mamilla had remained free. This leads to the conclusion that while a conservative, non-radical surgical treatment is fundamentally possible, the selection and the formation given to the patients must be done with great care. The problem of multicentricity remains. Long-term comparisons have not been made so far.
Epithelial cell differentiation is accompanied by biochemical and immunological changes of cytoplasmic components. Antibodies against filamentous and nonfilamentous substances of epithelial cells are helpful for the visualization of the gradual maturation processes in different epithelia. The present study is concerned with differentiation characteristics of the normal cervical mucosa and, in particular, the squamocolumnar junction. Antibodies against tissue polypeptide antigen (TPA), large keratins (67K), and all keratin fractions were applied in this investigation. Antibody binding was revealed by indirect immunofluorescence. TPA was found to be characteristic for basal layer cells and undifferentiated reserve cells of the transformation zone. In contrast, 67K represent an indication of squamous differentiation and were only found in suprabasal cells of the ectocervical epithelium and in keratinizing cells of the transformation zone. Antibodies against all keratin fractions were seen to label all epithelial cells. The immunomorphological definition of epithelial compartments of the normal cervical mucosa supports earlier concepts of the physiological processes at the squamocolumnar junction and represents an interesting tool for studies of cervical neoplasias of various differentiations.
With respect to their pathomorphology, the ovarian tumors form a large scale of histogenetically different types presenting considerable variations in their biologic behavior and responsiveness to radiologic and cytostatic therapy. The WHO classification contains eight major groups of malignant tumors. About 70% of them are common epithelial tumors. These tumors are the prototype of the ovarian cancer. Progress in early diagnosis can be expected because of recent developments in medical technology. Imageproducing physical methods like ultrasonography and computed tomography are more and more applied in order to obtain an exact preoperative diagnosis and for posttherapeutic check-up. A detailed knowledge of the tumor morphology is necessary for the application of these methods. Due to the multitude of different tumor types, ovarian tumors are paradigmatic for a selective tumor therapy. This is only possible after pretherapeutic differentiated histologic clarification.