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F T Bosman

Publications and source records attributed to F T Bosman.

At least 217 records · Page 12Linked to original sources

Immunocytochemical detection of basement membrane antigens in the histopathological evaluation of laryngeal dysplasia and neoplasia.

Immunocytochemical detection of intrinsic components of the basement membrane (type IV collagen and laminin) was performed in biopsies of carcinoma in situ, dysplasia and hyperplasia of the laryngeal mucosa. We found a distinct and continuous basement membrane, containing both laminin and type IV collagen, at the border between epithelial cells and mesenchymal stroma in normal as well as in hyperplastic and dysplastic mucosa. In contrast, irregular discontinuities were found in some cases of carcinoma in situ and in invasive carcinoma. In addition, immunoreactivity for intracytoplasmic basement membrane components was noticed occasionally in neoplastic epithelial cells. In areas of inflammation, infiltration of leucocytes into the epithelium was occasionally accompanied by sharply defined small interruptions of the basement membrane. Our results indicate that immunohistochemical detection of basement membrane components can be of value for the demonstration of microinvasive growth in laryngeal cancer.

Antigens↗

Patterns of basement membrane deposition in benign and malignant breast tumours.

We have examined epithelial basement membranes in tissue samples of seven normal breasts, 64 benign breast lesions and 63 malignant breast tumours by immunocytochemistry, using polyclonal antisera specific for type IV collagen. In normal breast tissue as well as in all benign tumours a continuous basement membrane was found at the epithelial stromal interface. In benign proliferative lesions, epitheliosis and papillomatosis could be more accurately distinguished with basement membrane staining. This approach also facilitated the differentiation between sclerosing adenosis and tubular carcinoma, since the tubules in sclerosing adenosis are surrounded by a continuous basement membrane whereas in tubular carcinoma basement membranes are almost entirely absent. In radial scar lesions the tubules were always surrounded by intact basement membranes, which underlines the fact that these are benign lesions. In breast carcinoma we could not detect a relationship between histological grade and the extent of basement membrane deposition. However, in different tumour types the basement membrane alterations varied. In infiltrating lobular carcinoma of the alveolar type, fragments of basement membrane were found, whereas in the classic and trabecular type, basement membranes were absent, suggesting that the alveolar type may be an intermediate phase in the progression of lobular carcinoma in situ to infiltrating lobular carcinoma. It is concluded that basement membrane immunocytochemistry, using antibodies to type IV collagen, is useful in the differentiation between benign and malignant breast lesions and in the classification of breast neoplasms.

Adenocarcinoma↗

Flow cytometric determination of DNA ploidy level in nuclei isolated from paraffin-embedded tissue.

Nuclei, isolated from paraffin-embedded tissue, were stained with propidium iodide (PI) and found suitable for DNA analysis by flow cytometry (FCM). DNA-derived fluorescence intensity, however, was always decreased and had a much higher intersample variability as compared to results obtained with fresh material. Using chicken red blood cells (CRBC) as a model system, we found the lower fluorescence intensity to be due to the formalin fixation step in tissue processing. The intersample variability was found to be at least partly caused by variations in the duration of fixation. Overnight trypsinization improved the fluorescence intensity but did not reduce the intersample variability. Under all conditions tested PI binding to CRBC appeared to be saturable. Since fresh diploid or red blood cells could not be used to standardize DNA histograms, an alternative approach was developed in which nuclei from paraffin-embedded normal and tumor tissue of the same specimen were mixed. With this method DNA indices (DI) of 24 colorectal cancers were found to be closely correlated (r = 0.9877, P less than 0.001) with DI obtained with fresh tumor tissue from the same patients. The correlation of the percentages of S-phase nuclei between paraffin-extracted and fresh samples (r = 0.5875, P less than 0.05) was as high as could be expected, taking sampling differences into account. This method is an important tool for the retrospective analysis of FCM-derived DNA parameters in relation to diagnosis and prognosis of neoplasms.

Animals↗

Immunohistochemical localization of adenosine deaminase complexing protein in intestinal mucosa and in colorectal adenocarcinoma as a marker for tumour cell heterogeneity.

Adenosine deaminase complexing protein (ADCP), a dimeric glycoprotein, has been reported to be decreased or deficient in transformed or cancer-derived cell lines, indicating its potential significance as an indicator of malignant transformation. A similar deficiency was reported in total homogenates of tumours of colon, kidney, lung and liver. In previous biochemical studies we failed to confirm the consistent reduction in ADCP concentration in cancer tissues. A possible explanation for our findings was thought to be intercellular heterogeneity in ADCP expression in individual tumour cells. To study ADCP expression in individual cells, we developed an immunohistochemical method which was applied to tissue sections. Paraformaldehyde--lysine--periodate (PLP) solution was found to be a suitable fixative. Fixed tissue samples were paraffin-embedded, sectioned and stained for ADCP, using an indirect peroxidase-labelled antibody procedure. The protein was localized in normal colonic mucosa, mainly in the brush border region of the luminal epithelium and in cytoplasmic granules. Intense ADCP immunoreactivity was found also in the basal part of some cells. In cancer cells, three staining patterns were observed: membranous, diffuse cytoplasmic and granular cytoplasmic. The adenocarcinomas exhibited significant intratumour and intertumour heterogeneity in their staining types. Further studies on ADCP expression in colorectal cancer in relation to clinical and histopathological characteristics are warranted in order to fully evaluate the potential significance of ADCP as a cancer associated antigen.

Adenocarcinoma↗

What's new in endocrine factors of tumor growth?

In this review some aspects of endocrinological factors in cancer are discussed. The first part addresses the determination of steroid hormone receptors in cancer of the breast. The importance of steroid hormone receptor determination for the clinical management of breast cancer patients is emphasized. Current methods for receptor measurement are critically evaluated and it is concluded that rigorous standardization of tissue handling procedures and of radiochemical methodology is mandatory to improve the reliability of the presently available methods. The development of new techniques for receptor determination has been met with high expectations. Monoclonal antireceptor antibodies in principle allow the development of a radioimmunoassay but are not widely available as yet. Histochemical methods for receptor localization have so far failed to meet accepted criteria of specificity. Therefore radiochemical determination at present remains the only reliable method. The second part addresses the production of peptide hormones by endocrine tumours of the gastroenteropancreatic (GEP) system and by non-neuroendocrine neoplasms. In the endocrine tumours of the GEP system a wide range of peptide hormones can be detected by immunocytochemistry, but most frequently the pattern of hormone production is comparable with that in the normal organ of origin. Clinical symptoms of excess hormone production occur much less frequently than hormone production is found by immunological methods and is usually caused by one hormone. It is proposed that these neoplasms are classified according to the hormone which causes the leading clinical symptoms and/or the hormone with the highest serum level. Peptide hormone producing cells in classical carcinoma are an intriguing phenomenon which has shed some new light on the embryological origin of neuroendocrine cells in the relevant organs and also on the histogenesis of neuroendocrine as well as non-neuroendocrine neoplasms.

Adenoma, Islet Cell↗

Immunofluorescence detection of liver cell membrane autoantibodies using PLC/PRF/5 cells.

Detection of liver cell membrane autoantibodies is routinely performed by immunofluorescence testing of patient sera on rabbit hepatocyte suspensions. We have investigated the possible use of cells from the PLC/PRF/5 human hepatoma cell-line. These cells were employed as substrate in an immunofluorescence test which was compared with the conventional rabbit hepatocyte assay. We found a close correlation between the results obtained with these different substrates on visual reading. We furthermore compared visual reading of immunofluorescence preparations with flow-cytometrical analysis of immunostained cell suspensions. The results with these different methods were largely confirmatory. The PLC/PRF/5 cells are easily available and should therefore be regarded as a highly valuable new substrate for detection of liver cell membrane autoantibodies. Flow cytometry appears to be a technically simple and reliable method for quantitative analysis.

Animals↗

Neuroendocrine differentiation in basal cell carcinomas: a retrospective immunohistochemical and ultrastructural study.

Recent investigations have suggested that in addition to basaloid cells, basal cell carcinomas (BCC) may also contain Langerhans cells and neuroendocrine cells. In order to establish the relative frequency of neuroendocrine differentiation in BCC, we performed a retrospective study of 50 consecutive BCC using conventional histochemical, immunocytochemical and ultrastructural methods. Argyrophil staining according to Grimelius was used for initial identification. Tumors containing argyrophil cells, as well as randomly selected tumors without these cells, were immunocytochemically stained with a panel of antisera against neurohormonal peptides. Only 2 tumors with argyrophil cells showed occasional somatostatin immunoreactivity; peptide hormone immunoreactivity could not be detected in any of the others. The somatostatin immunoreactive tumors, as well as 3 others, were subjected to electronmicroscopy to study the presence of dense-core secretory granules. However, these characteristic intracytoplasmatic structures could be detected in none. It is concluded that if neuroendocrine differentiation exists at all in BCC, it must be extremely rare. Our results indicate that reliable identification of multiple lines of differentiation in neoplasms can only be performed using combinations of (immuno) histochemical and ultrastructural techniques.

Basal Cell Carcinoma↗

Basement membranes in cancer.

Basement membranes are ubiquitous tissue constituents which occur as supportive structure adjacent to epithelium, endothelium, mesothelium and also around smooth as well as striated muscle cells, Schwann cells and fat cells. In various types of cancer, basement membranes have been extensively studied by electron microscopy. Often basement membrane interruptions were seen in invasive neoplasms but in some tumors the neoplastic cells were surrounded by a continuous basal lamina. Recent immunocytochemical studies have shown that in invasive carcinomas the neoplastic cells often lack a continuous basement membrane. This may be caused by catabolic activity of invasive tumor cells, which have been shown to produce specific collagenases, or by insufficient production and/or extracellular assembly of basement membrane components by the neoplastic epithelial cells. In diagnostic histopathology, immunocytochemical staining of basement membrane components such as type IV collagen and laminin may help to distinguish between noninvasive (benign or in situ) and invasive lesions. Furthermore, in carcinomas the extent of the expression of basement membrane components may be correlated with the degree of differentiation of the neoplastic cells. Finally, in soft tissue tumors, basement membrane staining may be helpful for the differentiation of basement membrane producing neoplasms (e.g. of vascular, neural, smooth muscle or striated muscle origin) from non-basement membrane producing neoplasms (e.g. of fibroblastic origin).

Basement Membrane↗

Gastrointestinal cancer-associated antigen (GICA) immunoreactivity in colorectal carcinoma in relation to patient survival.

Immunoreactivity of gastrointestinal cancer-associated antigen (GICA) was studied in tissue sections of 311 colorectal cancer patients and the results were correlated with data on patient survival. The group of uniformly GICA-positive tumours (10.6%) tended to behave more aggressively than focally positive (53.4%) and GICA-negative tumours (36.0%), also when stratified for stage of tumour extension and histological grade. This trend, however, did not reach statistical significance, perhaps as the result of a bias introduced by the relatively small number of GICA-positive cases. There appeared to be no significant difference in clinical course between patients with GICA focally positive or GICA-negative tumours (together comprising 89.4% of the total population studied). Further studies including a larger number of patients and longer follow-up periods are needed to validate the suggestion that GICA-positive colorectal carcinomas might show a more aggressive behaviour than tumours displaying other modes of GICA expression. However, the results of our study suggest that GICA immunoreactivity in colorectal carcinoma tissue is unlikely to be a sensitive, independent parameter for the prediction of prognosis in individual patients.

Antibodies, Monoclonal↗

Radiochemical determination of estrogen receptors in cryostat sections of target tissues.

A radioreceptor assay on unfixed cryostat sections has been developed. Mounted and dried sections were incubated with radiolabeled estradiol in the absence and presence of an excess of diethylstilbestrol and washed with buffer. Binding of radiolabel to sections was measured by direct liquid scintillation counting. Also protein-bound radioactivity which eluted from the sections was determined with a dextran-coated charcoal assay. Parallel sections were used for histological staining and protein determination. Scatchard analysis showed the presence of specific saturable binding sites for estradiol with dissociation constants in the 0.1-1.5 nM range. It is concluded that these high affinity and limited capacity (type I) binding sites represent estrogen receptors. The ligand-binding activity of section-bound estrogen receptors did not decrease upon dry storage up to 20 h at 4 or 23 degrees C prior to assay. During aqueous incubation a significant amount of receptor, representing about 40-60% of the total tissue content, elutes from the sections. Steroid specificity was proven by incubation with excess androgen, progestogen or corticoid instead of diethylstilbestrol or estradiol. With these ligands no significant competition was found. Tissue specificity was demonstrated by a very low level of specific estradiol binding to cryostat sections of rat skeletal muscle, spleen and intestine and by a moderate level in rat liver.

Animals↗

The value of secretory component (SC) immunoreactivity in diagnosis and prognosis of colorectal carcinomas.

Immunoreactivity of secretory component (SC) was tested in routinely processed tissue specimens of 314 colorectal cancer patients and correlated with clinicopathologic parameters, such as stage and histologic grade of the tumors as well as survival data of patients. In 22% of the carcinomas almost all tumor cells were SC positive, 36% of the tumors showed SC immunoreactivity in a focal, heterogeneous pattern, whereas in 42% of the carcinomas SC immunoreactivity did not occur. Uniformly SC positive carcinomas demonstrated a tendency to occur more frequently in the low stage and grade carcinomas, whereas uniformly SC negative neoplasms showed the reverse trend. These trends were only statistically significant for stage. Focal SC immunoreactivity (SC heterogeneous tumors) was not correlated with stage nor with grade. Furthermore, inclusion of SC heterogeneous tumors in the analysis of survival data obscured the statistical significance observed in the correlation of SC immunoreactivity status and patient survival in uniformly SC positive or negative tumors. It is concluded that the prognostic value of SC immunoreactivity patterns in colorectal carcinoma tissue appears to be limited due to the occurrence of a substantial proportion of tumors with heterogeneous SC expression and is of less significance than staging. Nevertheless, determination of the SC immunoreactivity status may be of additional value for the identification of a subpopulation of patients with a more favorable prognosis.

Cell Transformation, Neoplastic↗

Immunocytochemical localization of neuroendocrine hormones and oncofetal antigens in ovarian teratomas.

The presence of neurohormonal peptides, human chorionic gonadotropin (hCG), alpha-fetoprotein (AFP), and carcinoembryonic antigen (CEA) was evaluated using immunocytochemical techniques in 170 benign cystic teratomas and 19 solid teratomas. The latter ranged from grade 0 to 3. The presence of hCG, AFP, and CEA was associated with a high histological grade and may therefore play a role in the grading of solid teratomas. Gastroenteropancreatic neuroendocrine cells frequently occurred in cystic teratomas without coexisting neural tissue. This finding is contrary to the neural crest origin previously suggested by other investigators and is in accordance with an endodermal origin of these cells.

APUD Cells↗

The effect of duct obliteration on the histology and endocrine function of the canine pancreas.

Although duct obliteration is a safe and effective method for ablation of exocrine secretion in segmental pancreas transplantation, it remains to be clarified whether its effects are restricted to the exocrine tissue. In 20 dogs (beagles 9-15 kg) the right lobe of the pancreas was removed and the ductal system of the left lobe was injected with the duct-obliterants neoprene (6 dogs), polyisoprene (6 dogs), or prolamine (8 dogs). In this study, i.v. glucose tolerance tests (the results of which are expressed in K values) and relaparotomies for taking biopsies were performed at 1, 3, and 12 months after duct obliteration. Biopsies were studied histologically and immunohistochemically in a qualitative and semiquantitative fashion. Three prolamine-injected dogs developed diabetes. All other dogs maintained normal fasting blood glucose levels but showed reduced K values at 1 month after duct obliteration. Further deterioration of glucose tolerance was not observed up to 12 months. Differences in K values depending on the type of obliterant were insignificant at all intervals. The exocrine tissue was completely replaced by fibrosis at 3 months after duct obliteration, and the architecture of the islets was disrupted. Morphometrical analysis of relative numbers of different endocrine cell types showed transient changes at 1 month after duct obliteration, but did not differ from unmodified controls at 12 months. We conclude that the effects of duct obliteration are not restricted to the exocrine pancreatic tissue, but that the endocrine pancreas is interfered with as well. Changes in islet function and histology are brought about during the first month after duct obliteration and stabilize thereafter.

Animals↗

Adenocarcinoma of the endometrium with glassy-cell features--immunohistochemical observations.

A case of adenocarcinoma of the endometrium with glassy-cell features is reported and histochemical and immunohistochemical data are provided together with a review of the relevant literature. The microscopical features of glassy-cell carcinoma appear to be highly characteristic and diagnostic. The tumour is considered to be a distinctive and poorly differentiated type of adenosquamous carcinoma originating in the cervix or the endometrium. We studied the expression of several differentiating characteristics and detected the presence of secretory component and lysozyme in some tumour cells, whereas keratin and prekeratin were consistently absent. Since in normal uterine mucosa immunoreactivity for lysozyme is restricted to endocervical and isthmic epithelium, the presence of this antigen in the tumour would favour an endocervical or isthmic origin of the tumour cells. Furthermore our results suggest that this peculiar type of tumour is not poorly differentiated and that the assertion that glassy-cell carcinoma is a variant of adenosquamous carcinoma is open to doubt.

Adenocarcinoma↗