Biomedical subjects

C Decaestecker

Publications and source records attributed to C Decaestecker.

At least 19 recordsLinked to original sources

PubMed2000

S100 proteins in Corpora amylacea from normal human brain.

Corpora amylacea (C.A.) also named polyglucosan bodies (P.B.) are one of the hallmarks of normal brain aging. Although their functions are not yet clear, C.A. increase in number in patients suffering from neurodegenerative diseases. C.A. contain 88% of hexoses and 4% of proteins. Most of the proteins in C.A. are aging or stress proteins such as heat shock proteins, ubiquitinated proteins and advanced glycation end products which are also proinflammatory products. Stimulated by the potential role played by some S100 proteins in the inflammatory process which may be triggered in C.A., we investigated, by immunohistochemistry, the presence of different S100 proteins (S100A1, S100A2, S100A3, S100A4, S100A5, S100A6, S100A8, S100A9, S100A12 and S100B) in C.A. from normal human brain. Among the ten S100 proteins analyzed, nine (S100A) were detected in C.A. Three S100 proteins (S100A8, S100A9, S100A12) which are highly expressed in activated macrophages and used as inflammatory markers were detected in C.A. S100A8 was, in addition, found in thick neuronal processes from the pons. One (S100B) could not be found in C.A. although it was highly expressed in astrocytes. In C.A., the staining intensity was estimated by computer-assisted microscopy and gave the following order: S100A1 congruent withS100A8 congruent with S100A9>S100A5> or =S100A4>S100A12>S100A6> S100A2=S100A3. The potential inflammatory role played by S100 proteins in C.A. is discussed.

Adult↗

PubMed2000

Improving accuracy in the grading of renal cell carcinoma by combining the quantitative description of chromatin pattern with the quantitative determination of cell kinetic parameters.

The determination of grade and stage in renal cell carcinomas (RCCs) often fails to predict the actual clinical outcome for individual patients. The aim of the present work was to investigate whether it is possible to significantly improve the prognostic accuracy of the grading system by using the combination of two independent computer-assisted microscopy techniques. The first technique relates to the quantitative description of morphonuclear and nuclear DNA content features by means of the image analysis of Feulgen-stained cell nuclei, and the second quantitatively characterizes tumor growth by means of different cell kinetic parameters. These parameters consist of a duplication of a time-related parameter determined by means of the technique of using silver-stained proteins in interphase nucleolar organizer regions (AgNOR), a proliferation index determined by means of MIB-1 immunohistochemistry, and an apoptotic index determined by means of the terminal dUTP nick end labeling technique. The prognostic value of these quantitative features was investigated in a series of 60 RCCs. The quantitative analysis of Feulgen-stained nuclei made it possible to identify subgroups of patients with significantly different prognoses in both grade II and grade III RCCs. We labeled the RCCs associated with the most favorable prognoses as grade II- and III- and those with the least favorable ones as grade II+ and III+. The two most important kinetic variables to identify patients with different clinical outcomes were the MIB-1 index and the mean AgNOR area in the MIB-1-positive cells. Three significantly different survival curves were obtained for the 53 grade II and III RCC patients. Our results show that conventional RCC grading can be significantly improved by the quantitative analysis of Feulgen-stained nuclei, by cell kinetic parameter determination, and, more importantly, by combining the proliferation index with the mean AgNOR area parameter.

Antigens, Nuclear↗

PubMed2000

Glycohistochemical characteristics of nasal polyps from patients with and without cystic fibrosis.

OBJECTIVE: To investigate whether cystic fibrosis (CF)-related nasal polyps exhibit significantly distinct glycohistochemical characteristics when compared with single vs massive nasal polyps obtained from patients without CF. DESIGN: Glycohistochemical characteristics were identified by means of 8 histochemical probes, including 5 plant lectins (peanut, gorse seed, wheat germ, Maackia amurensis, and Sambucus nigra agglutinins), 2 animal lectins (14- and 16-kd galectins), and 1 neoglycoprotein (exposing the Thomsen-Friedenreich antigen). The binding of the 8 glycohistochemical markers was determined by means of computer-assisted microscopy. For each probe, 3 quantitative parameters were computed: the labeling index, which describes the percentage of tissue area specifically stained by a given marker; the mean optical density, which reflects the staining intensity; and the concentrational heterogeneity, which characterizes the level of heterogeneity of the staining intensity. SUBJECTS: A series of 61 nasal mucosa specimens was analyzed, including 6 normal cases, 23 single and 18 massive polyposis cases without CF, and 14 nasal polyps associated with CF. RESULTS: Normal and polyposal nasal mucosa differed in terms of the amounts and linkage types of sialic acids (revealed by the wheat germ, M amurensis, and S nigra agglutinins) rather than the characteristics of galactoside expression (monitored with the peanut agglutinin and 2 animal galectins). In contrast, nasal polyps markedly differed between patients with and without CF with respect to galactoside expression (revealed by the peanut agglutinin and the 14-kd galectin) and the display of binding site(s) for the neoglycoprotein. CONCLUSION: Normal and polyposal nasal mucosa differ essentially in sialic acid presentation, while nasal polyps from patients with CF have a higher level of various lectin-reactive galactoside residues than nasal polyps from those without CF.

Cystic Fibrosis↗

PubMed2000

Characterization of steroid hormone sensitivity in human breast cancers maintained ex vivo under organotypical culture conditions.

PURPOSE: The methodology we propose combines the immunohistochemical determination of the oestrogen and progesterone receptors (ER and PgR) with the characterization of the oestradiol- and progesterone-induced influence on cell proliferation in breast cancers in order to characterize their steroid hormone sensitivity at both the "static" and "dynamic" level. METHODS: ER and PgR have been immunohistochemically quantified by means of computer-assisted microscopy. Cell proliferation has been determined by means of tritiated thymidine autoradiography in tumour samples maintained in vitro as organotypic cultures. A series of 14 patients was investigated. RESULTS: Of the 14 breast cancers under study, one with an unequivocally "very ER-rich"/"very PgR-rich" immunohistochemical phenotype totally failed to exhibit any modification in its cell proliferation level after both oestradiol and progesterone stimulation. Two cases definitively associated with an "ER-poor"/"PgR-poor" immunohistochemical phenotype nevertheless responded noticeably to the dynamic stimulation of their cell proliferation by oestradiol and progesterone. While our series of cases covers 14 patients only, it suffices to demonstrate the limits of ER and PgR determination in characterizing steroid hormone sensitivity in breast cancer. DISCUSSION: The present work therefore presents an in vitro approach to test growth regulation of human breast cancer by steroid hormones. The clinical value of the present approach should be further determined by showing that steroid hormone-induced modifications in cell proliferation level are actually associated with clinical response.

Aged↗

PubMed2000

Big prolactin 60 kDa is overexpressed in salivary glandular epithelial cells from patients with Sjögren's syndrome.

Characterization of endogenous synthesis of prolactin (PRL) proteins and their cellular localization in labial salivary glands of patients with Sjogren's syndrome (SS) were achieved. PRL, PRL-receptors (PRL-R), and S100A6 protein were detected by immunohistochemistry. In situ prolactin synthesis was investigated in controls and SS patients by ex vivo incubation of minor salivary glands biopsies and immunoprecipitation assay. Increased PRL-immunoreactivity was found in cytoplasmic acinar epithelial cells in SS patients compared with normal subjects. PRL-R was distributed only in ductal epithelial cells in which S100A6 protein (a PRL-R-associated protein) was also present. PRL, PRL-R, or S100A6-immunoreactivity was not detected in infiltrating mononuclear cells. Immunoprecipitation demonstrated that PRL synthesis occurred in minor salivary glands with increased synthesis of two distinct PRL-like proteins (one major band at 60 kDa and a minor at 16 kDa) in SS glands compared with normal glands. Expression of PRL gene was demonstrated in SS salivary glands using RT-PCR. A positive correlation was found between the presence of PRL-like proteins in acinar epithelial cells of SS patients and clinical extraglandular manifestations. The presence of anti-Ro and anti-La antibodies also positively correlated with a higher percentage of PRL in acinar epithelial cells. In conclusion, PRL-like proteins are synthetized and overexpressed in glandular epithelial cells of labial salivary glands from SS patients and correlate with the aggressiveness of the disease.

Adult↗

PubMed2000

Differential expression of S100 calcium-binding proteins characterizes distinct clinical entities in both WHO grade II and III astrocytic tumours.

The computer-assisted microscopic analysis of Feulgen-stained nuclei enabled us to identify two subgroups of astrocytomas (WHO grade II) and two subgroups of anaplastic astrocytomas (WHO grade III) with significantly distinct clinical outcomes (Decaestecker et al. Brain Pathol 1998; 8: 29-38). The astrocytomas labelled in the present study as typical (TYP-ASTs) behaved clinically like real astrocytomas while atypical astrocytomas (ATYP-ASTs) behaved similarly to anaplastic astrocytomas. The anaplastic astrocytomas that we labelled as typical (TYP-ANAs) behaved clinically like anaplastic astrocytomas while atypical ones (ATYP-ANAs) behaved like glioblastomas. In the present study, we investigate whether some biological characteristics could be evidenced across these four groups of TYP- and ATYP-ASTs and TYP- and ATYP-ANAs. The data show that the levels of expression (immunohistochemically assayed and quantitatively determined by means of computer-assisted microscopy) of vimentin, the glial fibrillary acidic protein and the platelet-derived growth factor-alpha did not differ significantly across these four groups of astrocytic tumours. The level of cell proliferation (determined by means of both the anti-proliferating cell nuclear antigen and the anti-MIB-1 antibodies; P < 0.001 to P < 0.0001) differed very significantly between the astrocytomas and anaplastic astrocytomas, but not between the typical and atypical variants identified in each group. In sharp contrast, the levels of expression of the S100A3 and S100A5 proteins differed markedly in the solid tumour tissue in relation to the astrocytic tumour types and grades. In addition, while the levels of expression of S100A6 did not change in the astrocytic tumour tissue in relation to histopathological grade, the levels of expression of this S100 protein (but not those of S100A3 and S100A5) differed markedly in the blood vessel walls according to whether these vessels originated from low- or high-grade astrocytic tumours.

Adult↗

PubMed2000

Identification by quantitative chromatin pattern analysis of patients at risk for recurrence of superficial transitional bladder carcinoma.

PURPOSE: Based on the actual clinical outcomes of 132 fully documented patients with superficial transitional cell carcinoma of the bladder, we characterize the risk of recurrence and/or progression by computer assisted image microscopy applied to Feulgen stained nuclei. MATERIALS AND METHODS: Each tumor was characterized by the conventional grading and staging systems as well as by cytometry generated variables describing nuclear DNA content, nuclear morphometry and chromatin patterns. These data were submitted to discriminant analysis to establish a model distinguishing between 2 groups of patients. Group 1 included cases with remission for more than 60 months and group 2 cases presented with recurrence with or without progression within 12 months of transurethral bladder resection. This latter model was then validated by Kaplan-Meyer analysis of the full data set. RESULTS: As evidenced by Kaplan-Meier analysis, the discriminant factor generated by discriminant analysis of cytometry generated variables provided a cutoff value for distinguishing between low and high risks of recurrence (p <0.00001). In contrast, conventional grading and staging systems were not able to make such efficient distinction. CONCLUSIONS: These 2 groups can be used as references with which new cases can be compared to prognosticate disease behavior independently of histopathological grading and/or clinical staging.

Adult↗

PubMed2000

Characterization of ligands for galectins, natural galactoside-binding immunoglobulin G subfractions and sarcolectin and also of the expression of calcyclin in thyroid lesions.

The purpose of this study was to characterize ligands for galectins, natural galactoside-binding immunoglobulin G subfractions and sarcolectin and also the expression of calcyclin in various benign and malignant thyroid lesions. The extent of the binding of eight glycochemical probes was quantitatively assessed using computer-assisted microscopy on 76 thyroid lesions including 10 not-otherwise-specified multinodular goiters (S_MNG), 11 multinodular goiters with adenomatous hyperplasia (AH_MNG), 8 normomacrovesicular (NM_ADE) and 12 microvesicular (MIC_ADE) adenomas, and 9 papillary (P_CAR), 10 follicular variants of papillary (FvarP_CAR), 7 follicular (F_CAR) and 9 anaplastic (A_CAR) carcinomas. The 8 histochemical probes included 5 animal lectins (including galectins and sarcolectin), 1 polyclonal antibody (raised against calcyclin) and 2 immunoglobulin G subfractions from human serum with selectivity to alpha- and beta-galactosyl residues. The results show that multinodular goiters with adenomatous hyperplasia exhibited histochemical characteristics intermediate to those of normal multinodular goiters and microvesicular adenomas. Normomacrovesicular adenomas behaved very distinctly from microvesicular ones. Microvesicular adenomas were more closely related to differentiated thyroid carcinomas than any other type of benign thyroid lesions of epithelial origin. Papillary and follicular carcinomas seemed to represent the two extremes of the same biological entity with the follicular variant of the papillary carcinoma serving as a biological link between these two extremes. Anaplastic carcinomas behaved in a significantly different manner when compared to the differentiated forms of thyroid carcinomas. The results suggest that the patterns of expression of the glycoconjugates investigated in the present study may constitute useful tools for characterizing lesions in the human thyroid.

Adenocarcinoma↗

PubMed2000

Homocamptothecin, an E-ring-modified camptothecin, exerts more potent antiproliferative activity than other topoisomerase I inhibitors in human colon cancers obtained from surgery and maintained in vitro under histotypical culture conditions.

Topoisomerase I (Topo I) is overexpressed in cancer colon tissues compared with normal colon tissues. Several anti-Topo I inhibitors are already successfully used in the clinic. We illustrate here the antiproliferative activity of a new class of Topo I inhibitors, i.e., E-ring-modified camptothecins with enhanced lactone stability (L. Lesueur-Ginot et al., Cancer Res., 59: 2939-2943, 1999). Forty-three human colon cancers were obtained from surgical resection and maintained under organotypical culture conditions for 48 h. Cell proliferation was assessed in these ex vivo tumor tissue cultures by tritiated thymidine autoradiography. As a validation of the methodology, we first analyzed in our model the antiproliferative activity of two clinically active topoisomerase II (Topo II) inhibitors, Adriamycin and etoposide, which are not active for colon cancers; and three Topo I inhibitors, camptothecin (CPT) and two clinically active compounds (especially for colon cancers), i.e., topotecan and the active metabolite of irinothecan, SN-38. We then compared the antiproliferative activity of CPT, topotecan, and SN-38 against those of two investigational E-ring-modified camptothecins, i.e., BN80245 and BN80915. Three concentrations (1, 10, and 100 nM) were studied for each compound. The results indicate that the three Topo I inhibitors used as references, i.e., CPT, irinothecan, and SN-38, were much more active than the two Topo II inhibitors, i.e., Adriamycin and etoposide, with SN-38 being the most efficient. The two investigational compounds BN80245 and BN80915 exerted higher antiproliferative activity than the three anti-Topo I reference compounds, with the highest activity observed for BN80915.

Antineoplastic Agents↗

PubMed2000

Discrimination between dysplastic and malignant epithelium of the ampulla of vater based on quantitative image cytometric data.

OBJECTIVE: To assess the ability to associate histopathologic grading with objective criteria obtained by nuclear image cytometry in epithelium of the ampulla of Vater. STUDY DESIGN: Forty-one resected ampullary specimens were studied, including 8 dysplastic ampullomas together with 22 well-differentiated and 11 poorly differentiated ampullary adenocarcinomas. The nuclei were Feulgen stained and analyzed using a computer-assisted microscope, which generated 38 quantitative variables describing chromatin texture and nuclear DNA content (DNA ploidy level). These variables were explored by discriminant analysis to determine the most stable and informative variables. Univariate analysis was performed on the four most informative ones. The whole set of variables was also subjected to principal component analysis in order to characterize intragroup and intergroup heterogeneity. RESULTS: The univariate analysis defined two morphonuclear variables (related to nuclear chromatin distribution) discriminating between dysplasia and well-differentiated cancers. Aneuploidy occurrence was associated with discrimination between well-differentiated and poorly differentiated cancers. CONCLUSION: While alterations in chromatin distribution may be an early event in the malignant degeneration of this epithelium, alterations in nuclear DNA content should correspond to a later phenomenon. Quantification of these features can be exploited to assist in diagnosis.

Ampulla of Vater↗

PubMed2000

Labeled neoglycoproteins and human lectins as diagnostic and potential functional markers in salivary glands of patients with Sjögren's syndrome.

OBJECTIVE: The profile of glycans and their recognition by endogenous receptors (lectins) are increasingly attributed to disease process. Monitoring this can provide information on the pathogenesis of Sjögren's syndrome (SS). Commonly, plant lectins are employed for phenomenological glycan mapping. To go beyond this approach restricted to binding of exogenous probes, new markers measure ligand properties of glycans to human (not plant) lectins and the presence of sugar receptors completing a protein-carbohydrate recognition system. Carrier-immobilized sugar epitopes (neoglycoproteins) and purified human lectins establish this innovative panel. METHODS: The host defence molecules mannan binding lectin, serum amyloid P component, and the macrophage migration inhibitory factor-binding sarcolectin, selected for their involvement in cell destructive mechanisms, were purified and labeled. The plant lectins SNA and MAA were employed to monitor regulation of potential ligand sites for I-type lectins and galectins. Asialofetuin was tested as a "pan-galectin selective" probe. The specific binding characteristics were determined by quantitative morphometry and statistical analysis. RESULTS: Diagnostic information emerged from this analysis. The percentage of stained tissue area was significantly different between SS and control specimens after processing with GlcNAc and Man-bearing neoglycoproteins and the 2 tested serum lectins. For separation of cases of primary and secondary SS, the staining intensity with the asialoglycoprotein, sarcolectin, and the exogenous alpha2,6-sialylated glycan-binding lectin SNA was statistically significant. CONCLUSION: Saccharide-presenting probes to measure the cellular capacity to bind glycan epitopes and human lectins as sensors for endogenous binding sites have proven to be useful as diagnostic tools. We suggest the differences we observed reflect aberrations from the normal cellular homeostasis with relevance for the pathogenesis of SS and its manifestation as a primary or secondary syndrome.

Binding Sites↗

PubMed2000

In vitro and in vivo pharmacological characterizations of the antitumor properties of two new olivacine derivatives, S16020-2 and S30972-1.

S16020-2, a new olivacine derivative and a topoisomerase II inhibitor, has recently entered clinical trials. New analogues and derivatives have been synthesized from the S16020-2 compound. Preliminary data indicate that S30972-1, one of these S16020-2 derivatives, may exhibit a comparatively higher level of antitumor potency associated with an improved therapeutic index than does S16020-2. The antitumor activities of S16020-2 and S30972-1 were therefore characterized both in vitro and in vivo, with Adriamycin and etoposide chosen as reference compounds. The in vitro data show that S30972-1 is a topoisomerase II inhibitor, mediating its activity through an ATP-dependent mechanism such as S16020-2. The two olivacine derivatives exhibited similar activities in vitro at the levels of the global growth of six human cancer cell lines, of the induction of apoptosis, and of the G2 cell cycle phase arrest. The in vivo antitumor activity characterization included the use of two murine leukemia types (P388-LEU and L1210-LEU), two murine lymphoma-like models (P388-LYM and L1210-LYM), two mammary adenocarcinomas (MXT-HI and MXT-HS), and one melanoma (B16). The data show that S30972-1 is actually more efficient in vivo than S16020-2, a feature that may relate to the fact that S30972-1 is less toxic than S16020-2. The S30972-1 compound exhibited in vivo a level of antitumor activity that was also actually higher than that exhibited by Adriamycin and similar to that exhibited by etoposide.

Animals↗

PubMed1999

Computer-assisted analysis of epiluminescence microscopy images of pigmented skin lesions.

BACKGROUND: Epiluminescence microscopy (ELM) is a noninvasive clinical tool recently developed for the diagnosis of pigmented skin lesions (PSLs), with the aim of improving melanoma screening strategies. However, the complexity of the ELM grading protocol means that considerable expertise is required for differential diagnosis. In this paper we propose a computer-based tool able to screen ELM images of PSLs in order to aid clinicians in the detection of lesion patterns useful for differential diagnosis. METHODS: The method proposed is based on the supervised classification of pixels of digitized ELM images, and leads to the construction of classes of pixels used for image segmentation. This process has two major phases, i.e., a learning phase, where several hundred pixels are used in order to train and validate a classification model, and an application step, which consists of a massive classification of billions of pixels (i.e., the full image) by means of the rules obtained in the first phase. RESULTS: Our results show that the proposed method is suitable for lesion-from-background extraction, for complete image segmentation into several typical diagnostic patterns, and for artifact rejection. Hence, our prototype has the potential to assist in distinguishing lesion patterns which are associated with diagnostic information such as diffuse pigmentation, dark globules (black dots and brown globules), and the gray-blue veil. CONCLUSIONS: The system proposed in this paper can be considered as a tool to assist in PSL diagnosis.

Computer Simulation↗

PubMed1999

Improving the prognostic value of histopathological grading and clinical staging in renal cell carcinomas by means of computer-assisted microscopy.

The present work aims to refine prognosis in cases of renal cell carcinoma (RCC) by integrating a variety of parameters with the prognostic information provided by histopathological grading and clinical staging, carried out on a series of 97 RCCs. To this end, Feulgen-stained RCC cell nuclei were characterized by means of 38 variables describing nuclear DNA ploidy levels and morphology. All of these data were subjected to a principal components analysis. On the basis of this multivariate analysis, Fuhrman grade II was subdivided into grades II- and II+, and Fuhrman grade III into grade III- and III+. The same kind of subcategorization was performed in the case of the T2 and T3 clinical stages. The results show that the classification into grade II- and III- RCCs correspond to a more favourable prognosis than grade II+ and III+, to which shorter survival periods were attributable. Similar results were obtained for the subcategorization of the T2 and T3 clinical stages. Very simple biological characterizations of these grade- or stage-related RCC groups were obtained by means of a decision tree approach applied to the cytometry-generated variables. The resulting classification rules were validated on a new series of 18 patients and enabled very accurate predictions of survival.

Adult↗

PubMed1999

In vitro influence of lectins and neoglycoconjugates on the growth of three human sarcoma cell lines.

PURPOSE: The aim of our study is to investigate the in vitro effects of plant lectins, galectins and neoglycoconjugates on the proliferation of three human sarcoma cell lines. METHODS: Proliferation was assessed by means of the tetrazolium derivative reduction (MTT) assay. In addition, glycohistochemistry was used to make visible the plant-lectin-specific binding sites; the intensity of the lectin binding pattern was quantified by means of image analysis. RESULTS: Depending on the cell lines, the staining intensity and the percentage of labelled cells were different. With respect to growth modulation, the cell lines also responded differently to the probes used. Besides a predominant inhibitory effect elicited by the probes at 50 microg/ml, dose-dependent effects, including growth stimulation, were detectable in several instances. These effects relate to the animal galectins tested and several neoglycoconjugates, e.g. the lactose- and blood-group-A-trisaccharide-bearing probes. CONCLUSIONS: Endogenous lectins and lectin-reactive cellular glycoconjugates can apparently affect the regulation of the growth of human sarcoma cells. We suggest that these results are relevant for further histopathological monitoring in correlation with prognosis and in vitro assays to reveal possible clinical applications.

Cell Division↗

PubMed1999

The influence of L-triiodothyronine, L-thyroxine, estradiol-17beta, the luteinizing-hormone-releasing hormone, the epidermal growth factor and gastrin on cell proliferation in organ cultures of 35 benign and 13 malignant human thyroid tumors.

PURPOSE: To characterize the influence of six factors on human thyroid tissues at the cell-proliferation level. These six factors were the epidermal growth factor (EGF), the luteinizing-hormone-releasing hormone (LHRH), triiodothyronine, thyroxine, estradiol and gastrin. METHODS: Forty-eight human thyroid specimens were obtained from surgical resection and maintained alive for 48 h ex vivo (in vitro) under organotypic culture conditions. These specimens comprised 35 benign cases (17 multinodular goiters and 18 adenomas) and 13 cancers. Cell proliferation in the control and treated conditions (at a 5 nM dose) was assessed by means of the thymidine labeling index, which enables the percentage of cells in the S phase of the cell cycle to be determined in accordance with autoradiographic procedures. RESULTS: The results show that, of the six factors tested here, EGF significantly (P < 0.05 to P < 0.001) increased cell proliferation in the greatest number of cancers as compared to what happened with the remaining five. Each of these six factors significantly increased or decreased proliferative cell activity in some 10%-30% of the cases under study. CONCLUSIONS: Triiodothyronine, thyroxine, LHRH and gastrin may increase or decrease cell proliferation in human thyroid tissues, whether benign or malignant, to the same extent as other hormones and/or growth factors such as thyrotropin, EGF, insulin-like growth factor 1, transforming growth factor beta1 and estradiol the effects of which on thyroid cell proliferation are already well documented in the literature.

Adolescent↗

PubMed1999

Grading dysplasia in colorectal adenomas by means of the quantitative binding pattern determination of Arachis hypogaea, Dolichos biflorus, Amaranthus caudatus, Maackia amurensis, and Sambucus nigra agglutinins.

The current study deals with the setting up of a new tool that enables the benign versus the malignant nature of colorectal adenomas to be determined accurately. The 2 objectives are to determine (1) whether adenomas should, or should not, be included in a 2- or a 3-tier grading system, and (2) whether severe dysplasias and carcinomas in situ share common or different biological characteristics. The levels of expression of different types of glycoconjugates were characterized in a series of 166 colorectal specimens, including 14 normal, 90 dysplastic, and 62 cancerous cases. The glycoconjugate expressions were demonstrated for 5 lectins, namely, Arachis hypogaea (PNA), Dolichos biflorus (DBA), Amaranthus caudatus (ACA), Maackia amurensis (MAA) and Sambucus nigra (SNA). The glycoconjugates demonstrated by these 5 lectins belong to the family of the Thomsen-Friedenreich antigens. The binding patterns of the 5 lectins were quantitatively determined by means of computer-assisted microscopy. The quantitative data were submitted to discriminant analyses. Our results show that the specific glycochemical staining patterns could be identified unambiguously and without misclassification between benign (normal and low dysplasia) and malignant (ie, either as moderate/severe dysplasia, carcinoma in situ, or cancer) cases. The data also strongly suggested that (1) dysplasias seem to be distinguishable in 2 instead of 3 groups, that is, low versus moderate/severe (high); and (2) moderate/severe dysplasias are biologically distinct from carcinomas in situ. The methodology developed can be applied directly in routine diagnosis to identify moderate/severe dysplasia specimens already exhibiting features common to carcinomas, and which therefore should be treated consistently in view of the fact that our data strongly suggest that most moderate/severe dysplasias are still benign, whereas carcinomas in situ are real carcinomatous lesions.

Adenoma↗

PubMed1999

Galectin-3 and galectin-3-binding site expression in human adult astrocytic tumours and related angiogenesis.

Using computer-assisted microscopy, the present work aimed to quantitatively characterize the level of the histochemically detectable expression of galectin-3 and galectin-3-binding sites in sections of a series of 84 astrocytic tumours (including 22 grade II, 21 grade III and 41 grade IV specimens) and seven non-tumoural specimens used as controls. The presence of galectin-3 and reactive sites for this lectin were monitored by means of a specific polyclonal anti-galectin-3 antibody (aGal3) and biotinylated galectin-3 (Gal3), respectively. The pattern of expression of galectin-3-binding sites is compared to the pattern of expression of laminin (a potential galectin-3 ligand) revealed using a biotinylated anti-laminin antibody (aLam). Three variables quantitatively characterizing histochemical staining reactions were evaluated by means of computer-assisted microscopy for each of the 3 probes under study (aGal3, Gal3 and aLam). The labelling index (LI) is the percentage of tissue area specifically stained by a histochemical probe. The mean optical density (MOD) denotes staining intensity. The concentration heterogeneity (CH) feature expresses the concentrational spread of individual fields. The data obtained in the present study show that: (i) white matter of a non-tumoural brain expresses galectin-3 (and also galectin-3-binding sites); (ii) the level of galectin-3 expression significantly decreases in the majority of tumour astrocytes from low to high grade astrocytic tumours; while (iii) some tumour cell clones expressing high amounts of galectin-3 emerged with increasing levels of malignancy; and (iv) the level of accessible galectin-3-binding sites was apparently not heavily modified in the course of malignancy progression. In conclusion, the results obtained in the present study show that human astrocytic tumours are very heterogenous in their galectin-3 levels of expression. If high levels of galectin-3 determine the invasiveness potential of a tumour cell, then within a heterogenous tumour the presence of even a small, but actively proliferating number of tumour cell clones expressing high levels of galectin-3 can be expected to lead to tumour invasiveness.

Adult↗