[A normal cervical smear and yet cervical cancer].
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Adult↗
Biomedical subjects
F T Bosman
Publications and source records attributed to F T Bosman.
Association of aneuploidy in index adenomas with metachronous colorectal adenoma development and a comparison.
BACKGROUND: Features of index adenomas in the colorectum may be important for the prediction of metachronous adenoma development. METHODS: Complete colonoscopic follow-up for a mean period of 10 years was achieved in 70 of 124 patients after endoscopic polypectomy of an adenoma from the colorectum. On the basis of the clinical outcome, the patients were divided into three groups: Group I, patients who had a colorectum free of adenomas and cancer; Group II, patients who had one or more metachronous adenomatous polyps; and Group III, patients who subsequently had a colorectal carcinoma. The clinical characteristics of the patients were collected, and the neoplastic specimens were re-examined with regard to pathologic parameters and flow cytometrically determined nuclear DNA content. RESULTS: Aneuploid stemlines were found in 35% of the index adenomas. Significantly more aneuploid adenomas were found in the index adenomas of Group I patients than in the adenomas of Group II patients (r = -0.20; P = 0.05). However, in the index adenomas of Group II patients, aneuploidy was associated with villous architecture (P < 0.05) and inversely related to cellular atypia (P < 0.05). Such relations were not found in the adenomas from Group I. In addition, in the Group II adenomas, aneuploidy was found frequently in the more proximally localized adenomas in the large intestine. Remarkably, all adenocarcinomas of the Group III patients were localized in the right colon. No significant differences were found in ploidy and mean DNA index between index adenomas and metachronous adenomas of the Group II patients. However, the ploidy class of the index adenomas was found not to be related to that of the metachronous adenomas in the individual patients. CONCLUSIONS: These results demonstrate that DNA cytometry in adenomas alone is not helpful in the prediction of the possibility of the development of a metachronous adenoma. However, aneuploidy in a villous adenoma located more proximally in the colon might indicate a higher risk for metachronous neoplasia development. Index and metachronous adenomas are similar in DNA content but show no relation with respect to ploidy class.
Adenoma↗
Renewal of enterochromaffin cells in the rat caecum.
The localization, morphology, and neurohormonal peptide content of neuroendocrine cells have been extensively investigated. Relatively little is known about the kinetics of growth and differentiation of these cells. We studied the kinetics of enterochromaffin (EC) cells in the caecum of the rat, by applying the thymidine analogue 5-bromo-2'-deoxyuridine (BrdU), to identify cells in S-phase, administered in pulse-chase and synchronous continuous labeling experiments. By double indirect immunofluorescence staining of tissue sections, using antibodies against serotonin and BrdU, percentages of BrdU positive EC cells could be enumerated, from which cell-kinetic parameters were derived. The following conclusions were drawn: 1) EC cells are renewed by proliferation of EC cells and by recruitment from proliferating precursor cells. 2) Caecal EC cells appear to consist of a relatively rapidly renewing and migrating fraction (60-65%) with a turnover time of approximately 16 days and a relatively slowly renewing and possibly stationary fraction (35-40%) with an estimated turnover time of approximately 150 days. 3) Seventy percent of the EC cells are localized in the lower half of mucosal crypts, 30% in the upper half. After prolonged labeling the percentage of labeled EC cells in the lower crypt half always exceeds that in the upper crypt half. This decrease in labeled EC cells during migration towards the mucosal surface indicates loss of endocrine cells, possibly owing to loss of endocrine characteristics.
Animals↗
Oestrogen and progesterone receptor immunocytochemistry in human hyperplastic and neoplastic endometrium.
Proliferative disorders of the endometrium may be associated with autocrine and paracrine actions between stromal and epithelial cells. To determine whether the stromal-epithelial relation with respect to oestrogen receptor (OR) and progesterone receptor (PR) is disturbed in (pre)malignant endometrium immunocytochemical OR and PR expression was quantitated by computerized image analysis. This was studied in the stromal and epithelial cells of endometrial specimens diagnosed as hyperplasia (n = 14), atypical hyperplasia (n = 16), and adenocarcinoma (n = 33). Paraffin sections were used for optimal preservation of histomorphology. A progressive loss of OR and PR content occurred with increasing malignant transformation. Stromal cells in atypical hyperplasia (P = 0.0007) and well-differentiated adenocarcinoma (P = 0.0008) exhibited a relative loss of PR content as compared with epithelial cells (P = 0.036 and P = 0.17, respectively). In atypical hyperplasia, the decrease in stromal PR content was not in parallel with persistent stromal OR immunostaining. Furthermore, stromal PR expression in atypical hyperplasia was significantly (P = 0.004) lower than in the surrounding hyperplasia, whereas the stromal OR staining as well as the epithelial OR and PR staining did not differ significantly. These observations may reflect a disturbance in hormonal interrelationships between endometrial cells in the development of endometrial neoplasia, indicating that stroma may modulate epithelial growth by paracrine mechanisms.
Adenocarcinoma↗
L-CAM expression in normal, premalignant, and malignant colon mucosa.
L-CAM is a cell adhesion molecule which is expressed at the intercellular borders of most epithelial cells. L-CAM has been demonstrated to act as an invasion suppressor in carcinoma cell lines. In order to determine whether or not L-CAM expression might distinguish between invasive and non-invasive or metastatic and non-metastatic colon neoplasms, we studied L-CAM expression in normal colon mucosa, colon adenomas with various degrees of dysplasia, and colon carcinomas by immunohistochemistry, using the 6F9 monoclonal anti-L-CAM antibody. Normal mucosa showed evenly distributed distinct L-CAM immunoreactivity along intercellular borders. In adenomas and carcinomas, a similar though weaker expression was observed. This pattern showed a tendency to decrease in parallel with decreasing differentiation. However, no correlation was found with Dukes stage or area within the tumour. In some carcinomas, L-CAM was expressed at the luminal surface of the cells. In others, L-CAM expression was not found. These results suggest that L-CAM expression is disregulated or lost as an early event in the development of colon neoplasia and indicate that L-CAM expression does not correlate with invasive or metastatic potential.
Adenoma↗
Does ex vivo labelling of proliferating cells in colonic and vaginal mucosa reflect the S-phase fraction in vivo?
The ex vivo labelling of DNA-synthesizing epithelial cells in colonic and vaginal mucosa was compared with in vivo labelling. For this purpose, in vivo S-phase cells were labelled with [3H]thymidine (Tdr) and ex vivo labelling was continued by culturing tissue specimens in bromodeoxyuridine (BrdU). Various methods of tissue culture were employed in order to improve diffusion of medium (and BrdU) in the tissue. BrdU and 3H-TdR labelling were evaluated by immunohistochemistry and autoradiography respectively. Ex vivo labelling resulted in a patchy distribution of labelled cells, which did not correspond with the 3H-TdR labelling pattern obtained in vivo. Under the described conditions ex vivo labelling does not appear to be a reliable for estimation of the proliferative activities in vivo.
Animals↗
Bromodeoxyuridine (BrdU) immunocytochemistry by exonuclease III (Exo III) digestion.
A new procedure is described to generate single-stranded DNA by exonuclease III (Exo III) digestion for bromodeoxyuridine (BrdU) immunocytochemistry on tissue sections. We compared this procedure with the most widely used procedure of DNA denaturation with 2 N HCl. In vivo and in vitro pulse and continuous labelling of tissues and cells were used. The specimens were fixed in formalin, ethanol, glutaraldehyde, Carnoy's, Bouin's or Zamboni's fixative and embedded in paraffin or used unfixed as cryostat sections or cytospin preparations. After Exo III digestion, BrdU substituted DNA was detected irrespective of the fixation procedure applied. The optimal protocol for nuclease digestion appeared to be simultaneous incubation, of 10 Units Exo III per ml EcoRI buffer and anti-BrdU monoclonal antibody at 37 degrees C. The advantages of Exo III digestion for BrdU immunocytochemistry compared to acid denaturation were: less non-specific nuclear background reactivity, no DNA renaturation, less DNA loss, optimal nuclear morphology, increase in antibody efficiency and the possibility for simultaneous detection of acid-sensitive tissue constituents. Disadvantages of the Exo III digestion are decreased sensitivity and the need for more rigorous pepsin pretreatment. We conclude that Exo III digestion of DNA is an appropriate alternative for acid denaturation for BrdU immunocytochemistry on sections of pulse-labelled specimens.
Animals↗
NCI-H716 cells as a model for endocrine differentiation in colorectal cancer.
In colonic neoplasms, endocrine differentiation is encountered not only in carcinoid tumors but also in adenocarcinomas, where endocrine cells may represent a distinct line of differentiation in the tumor. The significance of endocrine differentiation in colorectal cancer is not well established, partly because of the paucity of tumor cell lines which can serve as a model for studying endocrine differentiation. In this report we describe the properties of NCI-H716 cells, a cell line derived from a poorly differentiated adenocarcinoma of the caecum, under various in vitro conditions and as xenografts in athymic mice. Phenotypical properties were immunohistochemically assessed using a panel of differentiation related antibodies, and also by Northern blot analysis and by electron microscopy. Receptors for biogenic amines and peptide hormones were analyzed by ligand binding assay. These studies show that: 1. NCI-H716 cells can be undifferentiated, or show endocrine, mucin-producing or "amphicrine" properties. 2. Endocrine differentiation of NCI-H716 cells preferentially occurs in xenografts in athymic mice, which suggests that mesenchymal elements induce endocrine differentiation. 3. NCI-H716 cells express large amounts of high affinity receptors for gastrin, serotonin and somatostatin and these substances can regulate growth. Thus, NCI-H716 cells form a suitable model for the study of endocrine differentiation in intestinal epithelium and of auto- or paracrine growth regulation in intestinal neoplasia.
Animals↗
Directional atherectomy for treatment of restenosis within coronary stents: clinical, angiographic and histologic results.
OBJECTIVES: The safety and long-term results of directional coronary atherectomy in stented coronary arteries were determined. In addition, tissue studies were performed to characterize the development of restenosis. METHODS: Directional coronary atherectomy was performed in restenosed stents in nine patients (10 procedures) 82 to 1,179 days after stenting. The tissue was assessed for histologic features of restenosis, smooth muscle cell phenotype, markers of cell proliferation and cell density. A control (no stenting) group consisted of 13 patients treated with directional coronary atherectomy for restenosis 14 to 597 days after coronary angioplasty, directional coronary atherectomy or laser intervention. RESULTS: Directional coronary atherectomy procedures within the stent were technically successful with results similar to those of the initial stenting procedure (2.31 +/- 0.38 vs. 2.44 +/- 0.35 mm). Of five patients with angiographic follow-up, three had restenosis requiring reintervention (surgery in two and repeat atherectomy followed by laser angioplasty in one). Intimal hyperplasia was identified in 80% of specimens after stenting and in 77% after coronary angioplasty or atherectomy. In three patients with stenting, 70% to 76% of the intimal cells showed morphologic features of a contractile phenotype by electron microscopy 47 to 185 days after coronary intervention. Evidence of ongoing proliferation (proliferating cell nuclear antigen antibody studies) was absent in all specimens studied. Although wide individual variability was present in the maximal cell density of the intimal hyperplasia, there was a trend toward a reduction in cell density over time. CONCLUSIONS: Although atherectomy is feasible for the treatment of restenosis in stented coronary arteries and initial results are excellent, recurrence of restenosis is common. Intimal hyperplasia is a nonspecific response to injury regardless of the device used and accounts for about 80% of cases of restenosis. Smooth muscle cell proliferation and phenotypic modulation toward a contractile phenotype are early events and largely completed by the time of clinical presentation of restenosis. Restenotic lesions may be predominantly cellular, matrix or a combination at a particular time after a coronary procedure.
Actins↗
Histochemical techniques for receptor localization.
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Autoradiography↗
Flow cytometric steroid receptor analysis.
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Antibodies, Monoclonal↗
Basement membranes in neoplasia.
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Animals↗
Polyploidy in pleomorphic adenomas with cytological atypia.
Occasionally, in fine-needle aspirates of pleomorphic salivary gland adenomas, considerable cytonuclear atypia is present, which may give rise to a false-positive diagnosis. In this study DNA cytophotometry was performed on Feulgen restained smears prepared from material obtained by needle aspirates of normal salivary glands (n = 4), pleomorphic adenomas with (n = 5) and without (n = 4) atypia and a carcinoma in a pleomorphic adenoma. The results showed a clear diploid DNA histogram in the specimens of normal salivary gland and pleomorphic adenomas without atypia. In contrast, in the pleomorphic adenomas with atypia a distinct polyploid pattern was present in three out of the five DNA histograms with DNA values in 2c, 4c and 8c ranges. In two of these cases a 16c peak was also present and in the two remaining cases tetraploidy was demonstrated. In the carcinoma a main stemline at 4c was found. This report once more emphasizes the possible atypia which may be present in FNA of pleomorphic adenomas of the salivary gland. The atypia is due to polyploidy in a histologically benign tumour.
Adenoma, Pleomorphic↗
Quality control in immunocytochemistry: experiences with the oestrogen receptor assay.
AIMS: To evaluate the feasibility of an interlaboratory quality control programme in immunohistochemistry. METHODS: Several pathology laboratories were asked to carry out immunohistochemical oestrogen receptor staining on a set of freeze dried cryostat sections of breast cancer tissue. The sections and protocols for staining and semi-quantitative scoring were mailed to the participating laboratories in two trials. The oestrogen receptor content of the breast cancer samples was determined by radioligand binding assay on the tumour cytosol. RESULTS: In the first trial 11 laboratories (response rate 60%) participated. Eight (73%) of the participants scored within a 95% confidence interval and all but one correctly classified the tumour as receptor positive. In the second trial all 20 participating laboratories (response rate 55%) correctly scored one tumour sample as negative and 18 of them (90% of respondents) correctly classified the two other tumour samples as receptor positive. In a quantitative evaluation a histochemical score within 95% confidence interval limits was provided by eight (40%) and 12 (60%) of the participants. CONCLUSIONS: Semiquantitative scoring of immunocytochemical staining is valuable for performing correlative inter-laboratory studies, although this scoring protocol may not be required for diagnosis or prognosis. Significant inter-laboratory variability exists, leading to qualitatively correct receptor classification in 100% of receptor negative and 80% of receptor positive cases, and quantitative agreement in only about half of the cases. The perceived variability is not caused by systematic differences in the choice of the immunocytochemical technique, or the mailing of freeze dried sections. Quality control programmes should be included in the standard procedures of each diagnostic immunohistochemistry laboratory.
Breast Neoplasms↗
Chromosomal localization of transfected genes by a combination of hot banding and fluorescence in situ hybridization.
We describe the combination of hot banding with fluorescence in situ hybridization as a rapid and efficient method to identify integration sites of transfected DNA sequences in chromosomes. As a test system we used SW480 EJ2, a clonal cell line obtained after transfection of SW480 with pSV2neoEJ, a plasmid containing a point-mutated, c-Ha-RAS oncogene. Nick-translated probes were compared with random primed-labeled probes to evaluate their relative efficiency in fluorescence in situ hybridization. The fluorescence signals were quantified in interphase nuclei by confocal scanning laser microscopy. Nick-translated probes were found to yield better results. Hot banding followed by fluorescence in situ hybridization localized the integration site of pSV2neoEJ in SW480 EJ2 at the site of a translocation on a marker chromosome Xp+. The combination of fluorescence in situ hybridization and hot banding can be used to (a) rapidly and efficiently analyze integration sites in large numbers of transfectants, (b) assess the clonality of transfected cell lines, and (c) localize the site of integration of transfected genes in the recipient genome.
Animals↗
Immunocytochemical analysis of oestrogen receptors and progesterone receptors in the human uterus throughout the menstrual cycle and after the menopause.
To obtain more insight into the relationship between cyclic and regional changes in steroid receptor expression and function-related changes in the various types of cell of the normal human uterus, we performed an immunocytochemical study on paraffin-embedded sections. The distribution and intensity of immunostaining for the oestrogen receptor and the progesterone receptor in the various types of cell were semiquantitatively scored. The data were statistically compared for the different phases of the menstrual cycle and after the menopause, and for the different regions of the corpus and (endo)cervix uteri. During the menstrual cycle, significant changes in oestrogen receptor score were observed in glandular and stromal cells of endometrium basalis and functionalis and in smooth muscle cells of the myometrium. In all types of cell, oestrogen receptor expression reached a maximum in the late proliferative phase. During the early secretory phase, oestrogen receptor staining declined sharply in stromal and smooth muscle cells, whereas, in glandular epithelium, oestrogen receptor expression decreased more gradually. During mid- and late-secretory phases, an increase in oestrogen receptor staining was also observed in predecidualizing stromal cells and smooth muscle cells. Progesterone receptor numbers changed significantly in glandular epithelium but not in stromal and smooth muscle cells. Glandular progesterone receptor expression reached a maximum in the early secretory phase and was then drastically reduced. During mid- and late-secretory phases stromal cells were moderately stained for progesterone receptor in contrast to epithelial gland cells which showed no or very weak staining. No regional variations in steroid receptor distribution in endometrium and myometrium were found.(ABSTRACT TRUNCATED AT 250 WORDS)
Endometrium↗
Neuroendocrine cells in colonic tumors.
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Adenocarcinoma↗
Prognostic significance of basement membrane deposition in operable squamous cell carcinomas of the lung.
Tumor histology, stage of disease, and performance status are the most important prognostic factors in squamous cell lung cancer (SqCLC). A potentially important descriptor is the pattern of tumor growth as reflected in the dissolution of preexisting or deposition of newly formed basement membrane (BM) around tumor cell nests. The possible correlation between the pattern of BM deposition and patient survival was investigated. Immunohistochemistry testing, using polyclonal antibodies to human type IV collagen, was done on tumor samples of 68 patients with operable Stages I or II SqCLC, and BM staining was scored semiquantitatively. More than 75% immunoreactivity was scored as extensive BM and less than 75% as moderate or limited BM. In six patients, no immunoreactivity could be detected. In 27 of 62 patients, extensive and, in 35 of 62 patients, moderate-limited BM deposition was found. This deposition had a significant effect on survival (P = 0.02). Cox regression analysis, including BM deposition and tumor stage, indicated that BM deposition might also have value as an additional independent prognostic indicator for survival (P = 0.02). Deposition of an appreciable amount of BM in the center of the SqCLC was a prognostically favorable sign, independent of tumor stage.
Basement Membrane↗