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Biomedical subjects

E Grundmann

Publications and source records attributed to E Grundmann.

At least 19 recordsLinked to original sources

Cancer morbidity and mortality in USA Mormons and Seventh-day Adventists.

Comparison of cancer morbidity and mortality rates between Mormons and Seventh-day-Adventists and the corresponding rates in the Federal Republic of Germany and the United States, reveals that mortality from malignant neoplasms in general is much lower in Mormons and Seventh-day Adventists than in the Federal Republic of Germany. The difference concerns in particular the tobacco-dependent tumors: compared to the rate of affected males in the Federal Republic of Germany, only some 25% of Mormon males are getting lung cancer. Similar patterns are found in laryngeal carcinoma. Tumors that are related to both alcohol and tobacco, such as carcinomas of tongue, pharynx and esophagus, are also significantly less frequent in Mormons. Malignant neoplasms of the female genital tract show distinct analogies: cervical carcinoma has a morbidity rate of only 26.7% of affected women in Germany. Accordingly, mortality rates of Mormons and Seventh-day Adventists show a significant lower level when compared with cancer data of lung, colon and rectum, and prostate from the best German cancer registry (Saarland). Some tumor rates are higher in Mormons, e.g. malignant melanoma, also all types of malignant lymphoma and myeloma. The life expectancy is generally elevated by 2-4 years in Mormons and Seventh-day Adventists. The association with the particular life style of both religious groups, especially the strict reduction of tobacco consumption, and factors of dietary and other habits is discussed.

Colorectal Neoplasms

Metastasizing eccrine porocarcinoma. Report of two cases with fatal outcome.

The clinical, histopathological and ultrastructural features of a metastasizing eccrine porocarcinoma are described in a 75-year-old woman and a 82-year-old woman. The previously not recognized tumors were identified by its distinct pattern of metastasis. Metastatic spreading was restricted for years to a circumscribed region of the skin. Histology and electron microscopy disclosed pronounced epidermotropism of the PAS-positive tumor cells. The characteristic pattern of dissemination obviously represents a homing phenomenon of the tumor cells derived from the intraepidermal sweat gland duct.

Adenoma, Sweat Gland

Autopsy diagnosis versus clinical diagnosis, particularly in malignant disease. Comparison of two periods: 1961-70 and 1978-87.

We present a comparison of autopsy records in the Institute of Pathology of Münster University during 1961-70 with those from 1978-87. The study was based on 11,716 autopsy cases in which reliable documentation of clinical diagnosis could be adequately correlated and compared with the respective autopsy diagnoses. In the decade 1961-70, 34% of the clinical diagnoses were correct, 15% were nearly correct and 23%, incorrect (24% had to be supplemented without relevance to therapy or prognosis, 4% side diagnoses). In the decade 1978-87, 50% of the clinical diagnoses were correct, 15% nearly correct and 18% incorrect (17% supplemented). With respect to malignant tumours, in 1961-70 clinical diagnoses were correct in 37% of cases and incorrect for 26%; in 1978-87, 47% were correct and 15% incorrect. This comparison covered all major tumour locations. The difference in incorrect clinical diagnoses between the two periods is statistically significant. With respect to infectious diseases, the concordance between clinical and autopsy diagnoses is even poorer. Lues (syphilis) is now rarely recognized in clinical diagnoses, even though it may be fatal; 50% of tuberculosis patients die from miliary tuberculosis without a correct diagnosis. Endocarditis in all its forms was underdiagnosed clinically in 75% of cases. These data provide substantial arguments in favour of autopsy control of clinical diagnosis, also including histological findings in biopsy specimens.

Autopsy

The proliferation behavior of bone tumors investigated with the monoclonal antibody Ki-67.

Specimens of several tumor entities at various grades of malignancy were selected from the Bone Tumor Registry of Westphalia for an immunohistological study of their proliferation behavior. Using the monoclonal antibody Ki-67 directed against a nuclear antigen present in all active phases of the cell cycle (G1, S, G2, and M), we were able to demonstrate the growth fractions in tissues with an atypical rate of proliferation, implying an increased risk of malignant transformation. In the 97 cases examined we found a good correlation of the biological proliferation behavior with the expression of the nuclear antigen Ki-67. Moreover, our immunohistological results are comparable with the data from the same tumor entities obtained by other methods such as flow cytometry and autoradiography. Thus the monoclonal antibody Ki-67 provides an excellent marker for labeling the growth fraction in a human tissue. Its practical impact lies in the differential diagnostic analysis of the proliferation rate in a given tumor and its possible grading, and in pre- or posttherapeutic monitoring of patients and the establishment of a prognosis.

Adolescent

Flow cytometric DNA analysis of bone tumors.

Flow cytometric DNA analysis was performed in a total of 203 bone tumors, benign and malignant. In more than 80% of cases the material studied was paraffin-embedded tumor tissue, mainly from the archives of the Bone Tumor Registry of Westphalia in Münster. Compared with ethanol-fixed fresh tumor samples, the variation coefficient in DNA histograms of the stored material was increased by a factor of 1.2-1.5, which means that resolution was decreased and that, in many cases, accurate cell cycle analysis was not feasible. However, the results of cell cycle analysis in bone tumors, even if performed on optimally fixed specimens, have to be evaluated with caution and full reference to the corresponding histological slides, since these histograms are apt to show various superpositions from the inflammatory infiltrate. The assessment of DNA ploidy is unimpaired if, in agreement with most researchers today, deviations smaller than +/- 10% from the diploid standard are still defined as DNA diploid, peridiploid, or pseudodiploid. The coefficient of variation should be kept as low as possible. If it is between 10% and 15%, the near-diploid stemlines with DNA indices of 0.9 or 1.1 may be hard to delineate. On account of the particularly marked regressive changes, the resolution of DNA histograms was most strongly impaired in chondromatous tumors, whereas it was mostly excellent in highly cellular viable tumor tissue, such as that from Ewing's sarcoma or osteoblastoma. On the whole, there was a distinct correlation between DNA ploidy and the biological behavior of bone tumors (Table 8). The highest rates of DNA aneuploidy were found in highly malignant OSs (18/21) and FSs (14/16), thus reflecting their poor prognosis. Of six juxtacortical OSs, three well-differentiated parosteal OSs and two periosteal OSs were DNA diploid, whereas one highly malignant surface OS and five highly malignant extraskeletal OSs, all DNA aneuploid, corresponded fully to the medullary OSs. Judging by preliminary results, adjuvant preoperative chemotherapy (COSS 80/82: Bösing et al. 1987) may reduce the rate of DNA aneuploidy and, consequently, of stem cell heterogeneity in general. A selective destruction of those stemlines that respond particularly to chemotherapy appears probable. In contrast to their high malignancy, Ewing's sarcomas showed an unexpectedly low proportion of DNA aneuploid stemlines (14/24). The comparatively favorable prognosis of MFH of bone is reflected in a lower rate of aneuploidies (2/10), which is also rather low (probably too low) when compared to our own data from soft tissue MFH (9/19).(ABSTRACT TRUNCATED AT 400 WORDS)

Bone Neoplasms

The cytogenesis of macrophages and osteoclast-like giant cells in bone tumors with special emphasis on the so-called fibrohistiocytic tumors.

Recent investigations have suggested that osteoclasts and osteoblasts belong to different cell systems: osteoclasts originate from hemopoietic stem cells, most probably via precursors of the mononuclear phagocyte system. Osteoblasts, however, arise from local mesenchyme. The present classification of bone tumors issued by the WHO, however, is still based on the assumption of osteoclasts and osteoblasts being merely different manifestations or differentiations of the same basic cell type. Consequently, histiocytes or macrophages as well as osteoclast-like giant cells are interpreted in most bone tumors as an autochthonous component of the tumor. In the present study, this theory is contradicted by histological immunohistological, electron microscopic, and autoradiographic-electron microscopic results on a larger number of osteosarcomas, chondromas, chondrosarcomas, chondroblastomas, aneurysmal bone cysts, giant cell tumors of bone, malignant fibrous histiocytomas, fibrosarcomas, desmoplastic fibromas, Ewing's sarcomas, fibrous dysplasias, nonossifying fibromas, and malignant hemangioenkdotheliomas of bone. In order to elucidate the role of macrophages and osteoclast-like giant cells, different monoclonal antibodies were applied to bone tumor specimens as markers of mononuclear macrophages and giant cells. The concept of what is called fibrohistiocytic tumors should be reconsidered. Immunohistological studies have shown that in malignant fibrous histiocytoma as well as in giant cell tumors of bone only a certain portion of macrophages will react with the highly specific antibodies, whereas the majority of tumor cells are negative. This finding alone suggests that the infiltration of macrophages is a reactive phenomenon. It is in agreement with earlier autoradiographic and electron microscopic investigations on giant cell tumors of bone, confirming that only the fibroblast-like tumors are actually proliferating. These data were verified in the present study with the aid of double labeling immunohistological techniques, using antibodies against mature tissue macrophages and others against a proliferation-associated nuclear antigen. Only the fibroblast-like cells, which do not react with the macrophage-specific antibody, will express the proliferation-associated nuclear antigen. Analogous results were obtained in malignant fibrous histiocytoma. We may infer from these results that the majority of these tumors must be neoplasms of local mesenchyme, mostly in fibroblastic differentiation, while the considerable number of macrophages is seen as a reactive phenomenon.(ABSTRACT TRUNCATED AT 400 WORDS)

Bone Neoplasms

Metastatic patterns of renal carcinoma: an analysis of 687 necropsies.

The metastatic behaviour of renal cell carcinoma has been studied in a series of 687 necropsies. The observations were consistent with the concept of "metastatic inefficiency", in that in 295 cases, including 25 with renal vein invasion, there were no detectable metastases. In the present series, renal vein involvement was not an important prognostic factor in stage 1 or 2 disease. In 73% of cases without lung metastases there were none in other sites, and in 84% of those with lung metastases there were others elsewhere, consistent with a metastatic "cascade" in which metastases first developed in the lungs and were later detected in other organs. However, the observations did not permit discrimination between anatomic cascades, in which other organs were seeded from metastasizing pulmonary metastases, and temporal cascades, in which the other were seeded at the same time as the lungs, but with fewer cancer cells. The patterns of arterial metastasis were consistent with the "seed-and-soil" hypothesis, and a novel index was developed to quantify differential organ "soils". The contralateral kidney was not the best soil for metastases from renal carcinoma. Given the presence of lymph node metastasis, the probability of heamatogenous metastasis is 90%. However, in the absence of nodal metastasis, approximately half the cases had haematogenous metastasis.

Adult

S-100 protein and neuron specific enolase (NSE) expression by chordomas in relation to the composition of their stromal mucosubstances.

The immunoreactivity of S-100 protein and neuron specific enolase (NSE.) was correlated with the composition of stromal glycosaminoglycans in chordomas and human notochords, in a combined histochemical and immunohistochemical study. We found that S-100 protein is negative in notochordal and chordoma cells in the absence of stromal mucosubstances or in the presence of small quantities of hyaluronic acid. The positivity of S-100 immunoreaction was found to be related to the presence of stromal glycosaminoglycans of the chondroitine sulfate A and C type. NSE. was found positive in cells presenting features of high metabolic activity. Consequently S-100 protein and NSE. immunoreactivity cannot have any cytogenetic implications, but they could be considered as markers indicating specific cell-stromal functional interactions.

Chordoma

Flow cytometric analysis of stemline heterogeneity.

The stemline heterogeneity of malignant tumors is closely connected with tumor aneuploidy. Both features can be characterized by either chromosome analysis or DNA cytophotometry. DNA analysis may be performed either by single cell photometry or by flow cytometry, of which the respective advantages and drawbacks are presented. Preliminary results of flow cytometric DNA analysis in malignant neoplasms are discussed; the possibilities of multiparametric measurement for quantitative analysis of various biochemical and antigenic properties in DNA stemlines are considered.

Aneuploidy

[Tumorous space occupying lesions of the scapula. An analysis of preoperative assessment of invasion].

The radiographic and histological morphology of 38 tumors lesions of the scapula are analyzed. Osteochondromas (n = 12), chondrosarcomas (n = 7), plasmacytomas (n = 4) and Ewing's sarcomas (n = 3) were the most frequent neoplasms. The radiographically determined growth rates allowed an estimate of the dignity in all cases. Benign lesions were only observed in the first five decades of life, and were mostly located in the scapular blade. Most tumors found in the acromion and in the glenoid region and all lesions diagnosed in the 6th to the 8th decades of life were malignant. In 63.2% of cases correct diagnosis of the type of lesion present was possible on radiographic examination.

Adolescent

Tumor heterogeneity in osteosarcoma as identified by flow cytometry.

Measurements of the cellular DNA content by flow cytometry were carried out in 25 untreated osteosarcomas to identify the frequency of DNA aneuploidies and heterogeneous DNA stemlines in relation to histopathology. Analyzing multiple specimens from each single tumor (2-16; median, 4), highly malignant osteosarcomas were found to express DNA aneuploidies in 18 of 21 cases (86%) with multiple aneuploid DNA stemlines in 10 cases (48%). In three paraosteal osteosarcomas, no DNA aneuploidy was detected and a significantly lower proportion of cells in S-phase was observed as compared to the highly malignant osteosarcomas (mean 8.6% vs. 18.8%; P less than 0.05). Like in the paraosteal osteosarcomas, no DNA aneuploidy and a low fraction of cells in S-phase was found in the predominant cell population of one of the very rare sclerosing small cell osteosarcomas, which also revealed a second DNA stemline with a DNA index of 2.0. These results demonstrate a high degree of DNA stemline heterogeneity in highly malignant osteosarcomas. The data emphasize the usefulness of DNA measurements for the characterization of bone tumors and indicate the possibility of discriminating highly malignant from low-grade osteosarcomas.

Aneuploidy

Biological characterization of human bone tumors. X. The proliferation behavior of macrophages as compared to fibroblastic cells in malignant fibrous histiocytoma and giant cell tumor of bone.

Seven giant cell tumors of bone and four malignant fibrous histiocytomas were studied immunohistochemically with different monoclonal antibodies to the mononuclear phagocyte system (MPS), to HLA-DR antigens, and to a proliferation-associated nuclear antigen (KI-67), in order to clarify the role of macrophages in these tumors. A part of the mononuclear cells stained positive with antibodies against the MPS. Antibody 25-F-9 against mature tissue macrophages showed the strongest reaction. The osteoclast-like giant cells also stained positive with this antibody. Fibroblast-like stromal cells, however, showed negative reactions to all antibodies against MPS cells. A double-labeling immunohistological technique was used to detect the proliferating cell population in these tumors. The fibroblast-like cells that were negative for MPS markers, were positively labeled with the monoclonal antibody Ki-67 against a proliferation-associated nuclear antigen, whereas a negative reaction to Ki-67 was seen in cells positive with antibodies to the MPS. These results support the concept that macrophages are a reactive population in these tumors, whereas the fibroblast-like mesenchymal cells are the proliferating tumor cells.

Antibodies, Monoclonal