Biomedical subjects
J H Holzner
Publications and source records attributed to J H Holzner.
[Retrospect on 24 years of the Pathological Institute].
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Nucleolar silver staining patterns and HLA-DR antigen expression in bronchial epithelial cells in chronic bronchitis.
Bronchial epithelial cells obtained by brush biopsy during fiberoptic bronchoscopy performed in 12 patients with chronic bronchitis and 12 healthy control subjects, were investigated for HLA-DR antigen expression and nucleolar silver staining patterns. In all patients with chronic bronchitis the number of bronchial epithelial cells positive to HLA-DR antigen was highly increased (> 90%), whereas in the controls only a few epithelial cells (< 10%) showed a weak HLA-DR antigen expression. Patients with chronic bronchitis showed an increased lymphocytic reaction compared to the control subjects. Both in the patients with chronic bronchitis and in the healthy controls the number of nucleoli was the same. The number of silver stained dots per nucleus was significantly higher in patients with chronic bronchitis than in the control subjects (7.70 +/- 0.87 as against 5.11 +/- 0.52; p < 0.0001). The intensity of the lymphocytic reaction correlated with the HLA-DR antigen expression and the increase in silver staining (Spearman's r = 0.543; p < 0.01). This indicates the influence of inflammation on the activation of epithelial cells derived from the respiratory tract.
Nucleolar silver staining patterns of lymphocytes in sarcoidosis.
Bronchoalveolar lavage lymphocytes from 15 patients with pulmonary sarcoidosis and 8 healthy controls were investigated for nucleolar silver staining patterns and lymphocyte subpopulations. Patients with sarcoidosis had increased numbers of silver stained dots versus controls (2.20 +/- 0.24 versus 1.78 +/- 0.07; p less than 0.001). The number of silver stained dots showed the strongest positive correlation to helper cells (OKT 4+) (r = 0.781; p less than 0.0001). These results may be interpreted as further evidence of lymphocytic activation, especially of helper cells (OKT 4+) in pulmonary sarcoidosis.
The role of autopsy in the control of mortality in Austria.
Maintenance of an acceptable autopsy rate is important for continuous quality control of the mortality statistics of a population, as well as for continuous quality control of clinical diagnosis in general. A high autopsy rate is of particularly great value for maintaining the quality of data on mortality from neoplastic diseases and, by feed-back, for ensuring the quality and accuracy of clinical diagnosis of malignant neoplastic diseases.
[Small cell carcinoma with sarcomatous stroma. Immunohistochemical study of an unusual carcinosarcoma of the bladder].
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[The high autopsy rate in Vienna].
In 1983 34% of all persons who died in the Republic of Austria were autopsied. We examined the frequency of postmortem examinations in the capital city, Vienna, between 1983 and 1987 in view of this high overall autopsy rate. The annual autopsy rate in all 9 pathology institutes and the department of legal medicine of the University of Vienna was on average 51 to 53%. There was a slight statistically verifiable decline in 1987. The reason for this high necropsy rate is that Austrian law permits the autopsies without the consent of next of kin if it appears indicated for medical, scientific or educational reasons; further more the fact, that the chairman of the department is at the same time the coroner for the hospital. A high autopsy rate is necessary to maintain a high standard of diagnostic accuracy even in modern medicine. The diagnoses were inaccurate or incomplete in 15% of all cases. The high autopsy rate is the basis for extremely accurate mortality and morbidity statistics and provides the basis for long range public health planning. Medical students develop an insight in disease patterns, which cannot be gained in any other way. The pathology departments of Vienna introduce a new city-wide computer-supported diagnostic file system, which will provide a baseline for comparative scientific studies.
Histologic tumor regression grades in squamous cell carcinoma of the head and neck after preoperative radiochemotherapy.
Forty-one patients with Stage III and IV squamous cell carcinomas (SCC) of the head and neck were treated preoperatively with mitomycin C and 5-fluorouracil and concomitant radiotherapy. Operation specimen were examined histologically, the percentage of vital tumor cells and devitalized tumor cells were graduated. The grade of regression was classified according to a four-stage scale. Tumor regression was elevated as good (Grades 1, 2) and bad (3, 4) response to combined preoperative therapy. After a follow-up of 18 to 30 months, 14 of 41 patients have experienced a locoregional recurrence; all these patients were bad responders (Grades 3, 4) to preoperative radiochemotherapy. There was a statistically significant correlation between tumor regression grade and probability of survival (P less than 0.001). The authors conclude that the prognosis of patients with pretreated SCC of head and neck depends on the histologic grade of tumor regression.
Histological grading of therapy induced regression in squamous cell carcinomas of the oral cavity. A morphological and immunohistochemical study.
Squamous cell carcinomas in the oral cavity and the oropharynx were diagnosed in 84 patients. After verification by biopsy, 79 of these patients were treated preoperatively with mitomycin C and 5-fluro-uracil, radiated and operated 3-5 weeks later. The effectiveness of adjuvant preoperative radio-chemotherapy was evaluated histologically. Serial sections of the entire tumor specimen were investigated and the percentage of vital cancerous tissue in the total tumor area was assessed. Regression was classified into four grades. Grades I and II were regarded as good response to adjuvant preoperative radio-chemotherapy, while grades III and IV stood for bad or no response. Morphologically questionable residual tumor infiltrates could be clarified by immunohistochemical methods with antibodies against vimentin, desmin and Lu-5. The histological assessment of the regression grade of operated tumor specimens allows a clinically relevant, morphologically exact and reproducible evaluation of the effect of preoperative radiochemotherapy.
Ki-67 immunoreactivity in breast carcinomas in relation to transferrin receptor expression, estrogen receptor status and morphological criteria. An immunohistochemical study.
The number of proliferating cells was determined by Ki-67 antibody in 107 primary breast carcinomas. These results were compared with transferrin receptor (TrfR) expression, estrogen receptor (ER) status, histologic type, tumor grade, size and axillary lymph node status. The percentage of Ki-67-positive cells ranged from 0.9 to 26.4%. The proportion of Ki-67-positive cells was highest in medullary carcinomas. Immunoreactivity of Ki-67 in relation to TrfR expression showed significant correlation (p = 0.0001). An inverse relationship between ER status and Ki-67 positivity existed (p = 0.0001). 88 cases were subjected to histologic grading. There was a significant relationship showing an increase of Ki-67 immunoreactivity with decrease of tumor differentiation (p = 0.0001). The distribution of Ki-67 reactivity in relation to tumor size and nodal status of the axilla revealed positive correlations (p = 0.02; p less than 0.05). In conclusion, the use of Ki-67 monoclonal antibody as a marker for cell proliferation represents a method to get kinetic data inhering prognostic value.
Histopathologic characterization of human breast cancer in correlation with estrogen receptor status. A comparison of immunocytochemical and biochemical analysis.
A detailed histopathologic analysis of 399 primary breast carcinomas was performed, and several morphologic features were correlated with the estrogen receptor (ER) status. In all cases ER status was determined immunocytochemically by estrogen receptor immunocytochemical assay (ER-ICA). In 359 carcinomas ER status was also biochemically determined. Invasive lobular, mucoid, and tubular carcinomas rather than ductal carcinomas were ER-positive more frequently in ER-ICA. Medullary and papillary carcinomas had corresponding lower or higher ER positivity, respectively, by both methods. The correlation of histologic grade and its single factors with ER status was statistically significant by both methods. Lymphocytic reaction to tumor showed a significant inverse relationship to ER status by both methods. A statistically significant higher number of ER-positive carcinomas in ER-ICA and dextran-coated charcoal assay (DCC) occurred when elastic tissue was present. Different associations were found between stromal content, tumor diameter, and ER status in DCC and ER-ICA, respectively.
Ultrastructural and immunohistochemical characteristics of lipid-rich carcinoma of the breast.
Five cases of lipid-rich carcinomas of the breast were investigated ultrastructurally and immunohistochemically for alpha-lactalbumin (ALA), lactoferrin (Lfr) and human milk fat globule membrane antigen (HMFG-2). Staining for ALA and Lfr showed intensive reaction on nearly all of the tumour cells whereas immunoreaction for HMFG-2 revealed positivity in single cells. All tumours were negative for steroid receptor content. Ultrastructurally the tumour cells showed numerous intracytoplasmic non-membrane bound lipid droplets which were often found within autophagocytic vacuoles. Neither rough endoplasmic reticulum nor Golgi complexes showed any sign of lipid synthesis. Extrusion of lipid droplets and extracellular lipid deposition was not observed. In conclusion, our findings do not justify the consideration of lipid-rich carcinoma of the breast as a clearly defined group of tumours with specific secretory activity. Therefore, the term lipid-rich carcinoma should be used in preference to lipid-secreting, unless there is evidence of active lipid secretion.
Prognostic significance of immunohistochemical parameters in breast carcinomas.
136 breast carcinomas were investigated immunohistochemically for alpha-lactalbumin (ALA), lactoferrin (Lfr), human milk fat globule membrane antigen (HMFG-2), transferrin receptor (TrfR), Ki-67 and epidermal growth factor receptor (EGFR). The relationships of pathologic features and steroid receptor status previously shown to be of prognostic significance and the immunohistochemical parameters were examined. It was found that estrogen receptor (ER) was inverse related to TrfR, Ki-67 and EGFR whereas progesterone receptor (PgR) was inverse correlated to Ki-67 solely. Tumor grading revealed significant correlations between TrfR, Ki-67 and HMFG-2 (inverse correlation). Tumor diameter showed correlation between Ki-67 solely. Moreover there were significant relationships between lymphoid infiltration and TrfR, Ki-67 and HMFG-2 (inverse correlation). The comparison of the immunohistochemical parameters showed correlations between Ki-67 and TrfR, Ki-67 and HMFG-2 (inverse correlation) as well as HMFG-2 and ALA. Therefore it is suggested that functional and tumor kinetic properties determined by HMFG-2, Ki-67 and TrfR may be an additional indicator with prognostic significance. On the other hand immunoreactivities of ALA in conjunction with HMFG-2 possibly indicates a subpopulation of breast carcinomas that may have to be investigated further. Moreover these results showed that lymphoid infiltration was correlated with Ki-67 reactivity as well as TrfR expression.
[Fine-needle puncture cytology of a solid cystic tumor of the pancreas].
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Expression of epidermal growth factor receptors (EGFR) on breast carcinomas in relation to growth fractions, estrogen receptor status and morphological criteria. An immunohistochemical study.
Epidermal growth factor receptor (EGFR) expression was determined on 88 primary breast carcinomas immunohistochemically. These results were compared with growth fractions (Ki-67 immunoreactivity and Transferrin receptor (TrfR) expression), histologic tumor type, tumor grading, axillary lymph node status and estrogen receptor (ER) status. 60.2% were EGFR positive. Cytomorphology predominantly revealed a fine granular staining pattern. Sometimes a concentrated immunoreaction on the intercellular and basal oriented cell poles could be observed. EGFR expression in relation to growth fractions, grading, tumor diameter and lymph node status showed no correlation, suggesting that EGFR status seems to be independent to tumor growth and morphological prognostic parameters. ER status revealed an inverse correlation to EGFR expression (Kendall's tau: -0.22804, p = 0.012). In this context, it stands to reason to investigate further how far determination of EGFR expression justifies the existence of different subpopulations of breast cancer cells with respect to prognostic value.
Pathology of renal cancer and its metastases.
The pretherapeutic classification of renal carcinomas includes the assessment of the tumor stage, the histological gross pattern, the cytological features, and the histopathological grading. As to the local tumor extension the perinephric invasion and renal vein involvement are the most important prognostic features. The presence of metastases dramatically alters survival. Histologically, compact, tubular, and papillary growth patterns are differentiated. Furthermore, the verification of the cell types in renal carcinomas is of prognostic significance. The clear cell carcinomas are opposed to the granular cell and spindle-shaped/pleomorphic types with poor prognosis. Rarely tumors consist of so-called "chromophobe" cells with finely reticular cytoplasms. They closely resemble clear cell carcinomas and exhibit a similar biological behaviour. According to the grade of atypia in renal carcinomas three grades of malignancy are distinguished. Conclusively, the tumor grade and the tumor cell type are the most reliable indicators of the malignant potential of renal carcinomas.
[Right heart failure as a clinical sign of pulmonary artery sarcoma].
A 43 year-old female patient was admitted on account of severe dyspnoea of several months' duration and thrombocytopenia. The clinical symptomatology was compatible with pulmonary embolism, but no source of embolization was found and heparin therapy did not lead to clinical improvement. Angiography of the pulmonary artery revealed multiple filling defects. Symptoms improved after treatment with cortisone and so a malignant process was assumed. The patient died from right ventricular failure before the diagnosis could be established. At autopsy a sarcoma of the pulmonary artery, obviously originating from the pulmonary trunk was found. Thrombocytopenia most probably resulted from consumption of platelets by a mechanism corresponding to the Kasabach-Merritt syndrome. The difficulties in the diagnosis of pulmonary artery sarcomas are discussed and the 69 previously published cases are reviewed.