Biomedical subjects

G A Meijer

Publications and source records attributed to G A Meijer.

At least 19 recordsLinked to original sources

PubMed2001

[Possibilities for further research of chronic wasting in dairy cows].

In this study, we reviewed the research that has been conducted in relationship with the problem of 'chronic wasting' in dairy cows in the Netherlands as was experienced during 1998 and 1999. Emphasis was drawn towards three aspects of this 'chronic wasting'; the definition, the magnitude, and the possible cause or causes. It appeared that a clear, objective definition of 'chronic wasting' in cows, and of farms with a problem of 'chronic wasting' cows is still lacking. Furthermore, the incidence (of the problem) was restricted to approximately 150 dairy farms at most. Currently, no farms with 'chronic wasting' cows are known. Combined with the uncertainty in the definition, this will hamper future research. Many of the studies were related to the hypothesis that the vaccination with the BHV1 marker vaccine had caused 'chronic wasting' in the cows. None of the results, however, substantiated this hypothesis. Other possible causes have hardly been investigated and further research would be needed to evaluate the role of nutrition, infectious agents, and genetics. However, due to the waning of the phenomenon, the availability of data and controls will be limiting.

Animal Nutritional Physiological Phenomena↗

PubMed2001

Rapid quantitative assessment of gastric corpus atrophy in tissue sections.

BACKGROUND/AIMS: Grading of Helicobacter pylori induced atrophic gastritis using the updated Sydney system is severely limited by high interobserver variability. The aim of this study was to set up a quantitative test of gastric corpus mucosal atrophy in tissue sections and test its reproducibility and correlation with the Sydney scores of atrophy. METHOD: Mucosal atrophy was assessed in 124 haematoxylin and eosin stained corpus biopsy specimens by two experienced gastrointestinal pathologists (EB, JL) according to the updated Sydney system as none (n = 33), mild (n = 33), moderate (n = 33), or pronounced (n = 25). In each specimen, the proportions of glands, stroma, infiltrate, and intestinal metaplasia in the glandular zone were measured as volume percentages using a point counting method. The optimal point sample size, intra-observer and interobserver reproducibility, discriminative power for degrees of atrophy, and correlations with H pylori status were evaluated. RESULTS: Counting 400 points in 200 fields of vision provided the smallest sample size that still had excellent intra-observer and interobserver reproducibility (r > or = 0.96). Overall, the volume percentage of glands (VPGL), infiltrate (VPI), and stroma (VPS) correlated well with the Sydney scores for atrophy (p < or = 0.003). However, no differences were found between non-atrophic mucosa and mild atrophy. No correlation was found between age and either the Sydney grade of atrophy or the VPGL or VPS. In non-atrophic mucosa and mild atrophy, H pylori positive cases showed a significantly higher VPI than did H pylori negative cases. A lower VPGL was seen in H pylori positive cases than in H pylori negative cases in the mild atrophy group. VPS did not correlate with H pylori status within each grade of atrophy. CONCLUSION: Point counting is a powerful and reproducible tool for the quantitative analysis of mucosal corpus atrophy in tissue sections. These data favour the combination of "none" and "mild" atrophy into one category, resulting in a three class grading system for corpus atrophy, when using the updated Sydney system.

Adult↗

PubMed2000

Helicobacter pylori-related and -non-related gastric cancers do not differ with respect to chromosomal aberrations.

Gastric carcinogenesis is strongly associated with Helicobacter pylori infection, but the underlying genetic mechanisms are largely unknown. The aim of this study was to correlate chromosomal aberrations in gastric cancer to H. pylori status and its different strains, as well as to histological type and other clinico-pathological variables. DNA from 46 gastric cancers (male/female 35/11, age 27-85 years) was extracted from formaldehyde-fixed, paraffin-embedded material and tested for chromosomal gains and losses by comparative genomic hybridization (CGH). Chromosomal aberrations with frequencies of 20% or higher were considered to be non-random changes associated with gastric cancer. The mean number of chromosomal events per tumour was 9.7 (range 0-27), with a mean of 3.2 gains (range 0-16) and 6.5 losses (range 0-15). Gains were most frequently found at chromosomes 8q and 13q (24% and 26%, respectively). Losses were predominantly found on chromosome arms 2q, 9p, 12q, 14q, 15q, 16p, 16q, 17p, 17q, 19p, 19q, and 22q (22%, 30%, 43%, 22%, 33%, 50%, 28%, 50%, 39%, 33%, 39%, and 37%, respectively). Common regions of overlap narrowed down to 2q11-14, 8q23, 9p21, 12q24, 13q21-22, 14q24 and 15q11-15. The mean number of gains was higher in tumours with metastases than in localized tumours (4.1 vs. 1.9, p=0.04). Tumours with a loss at 17p showed a higher number of losses than tumours without a 17p loss (9. 5 vs. 4.7 on average, p<0.001). Neither H. pylori status (+, n=25; -, n=21) nor H. pylori strain was correlated to the total number of events or to any specific chromosomal aberration, nor were there differences between intestinal (n=30) and diffuse (n=15) cancers or any other clinico-pathological variable tested. In conclusion, a complex of chromosomal aberrations is involved in gastric cancer, but their pattern does not depend on H. pylori status or strain, nor on the histological type of the tumour. The exact biological meaning of these aberrations in carcinogenesis needs further clarification.

Adult↗

PubMed2000

Helicobacter pylori gastritis in Africa.

* Helicobacter pylori gastritis progresses to gland loss and intestinal metaplasia in a considerable proportion of colonized subjects. * The progression to atrophic gastritis is a slow process, occurring with an incidence of 1-2% per year. * The progression of chronic H. pylori gastritis is the same in Africa as in Europe and South America. * This supports the concept of H. pylori as a causative factor of pre-neoplastic conditions of the gastric mucosa; other factors must play a modulating role in the progression to cancer. H. pylori gastritis may progress to atrophic gastritis and lead to the development of intestinal metaplasia, dysplasia and eventually gastric cancer in a minority of subjects. The available data on the kinetics of H. pylori gastritis are limited, but nevertheless very consistent. They suggest that the progression to gland loss or atrophic gastritis among H. pylori-positive subjects occurs at a rate of 1-2% per year. As H. pylori gastritis usually persists for life, a considerable proportion of H. pylori-positive subjects thus eventually show signs of gastric gland loss. The majority of these subjects progress to intestinal metaplasia. Despite these consistent findings in different areas of the world, the incidence of gastric cancer is only moderately related to the prevalence of H. pylori. An example is the so-called African enigma, referring to a low incidence of gastric cancer in certain countries of Africa, despite a high prevalence of H. pylori in all age groups. This is not due to differences in progression to atrophic gastritis; other yet unidentified factors therefore must play a role.

Adult↗

PubMed2000

Microarray techniques in pathology: tool or toy?

Microarray technology allows the simultaneous analysis of up to thousands of different genes in histological or cytological specimens. Although microarray technology has so far mainly been applied in the research setting, its clinical application in pathology is expected in the foreseeable future. This paper presents an overview of the technical "ins and outs" of microarray technology, and discusses several putative applications in diagnostic pathology, which include tumour classification, the prediction of responses to certain chemotherapeutical or hormonal agents, the biological staging of tumours, the risk assessment of premalignant lesions, and the detection of microorganisms.

DNA Mutational Analysis↗

PubMed1999

Analysis by comparative genomic hybridization of epithelial and spindle cell components in sarcomatoid carcinoma and carcinosarcoma: histogenetic aspects.

Sarcomatoid carcinomas and carcinosarcomas are histologically malignant biphasic neoplasms with an epithelial and a spindle cell component. Both a polyclonal and a monoclonal origin have been postulated for these tumours, but the latter has been favoured. For carcinosarcoma, the stem cell from which the epithelial and mesenchymal components are derived is expected to be more immature than the epithelial stem cell from which different components of sarcomatoid carcinoma originate, since in the latter, immunohistochemical or ultrastructural epithelial characteristics are still detectable. In the present study, comparative genomic hybridization was used to test the hypothesis that both tumour components in sarcomatoid carcinoma have more chromosomal aberrations in common than those in carcinosarcoma. From three sarcomatoid carcinomas originating from the urinary bladder and two carcinosarcomas from the pharynx, the epithelial and spindle cell components were microdissected and analysed for their respective chromosomal aberrations, using comparative genomic hybridization. High-level homology was seen in chromosomal aberrations between the different components in each tumour. This level of homology was even higher in the carcinosarcomas (65 and 91 per cent) than in both sarcomatoid carcinomas (21-51 per cent). The different phenotypic components of both sarcomatoid carcinoma and carcinosarcoma show a large overlap of chromosomal aberrations, strongly suggesting a monoclonal origin for all of these tumours. These findings do not support the hypothesis that the divergence between epithelial and spindle cell components occurs at an earlier stage in carcinosarcomas than in sarcomatoid carcinoma.

Carcinoma↗

PubMed1999

p21(Waf1/Cip1) expression and the p53/MDM2 feedback loop in gastric carcinogenesis.

Data are non-existent regarding coincidental alterations in the expression of p53 and its downstream target genes MDM2 and p21(Waf1/Cip1) in gastric carcinogenesis. An immunohistochemical study was therefore performed to examine the interrelationships of p53, MDM2, and p21(Waf1/Cip1) expression in a series of Caucasian early gastric carcinomas and precursor lesions. In normal gastric mucosa, chronic gastritis, and intestinal metaplasia, the surface cells expressed p21(Waf1/Cip1) in the absence of detectable nuclear p53 and MDM2 protein. Nuclear p53 protein accumulation was found in 60 per cent of the carcinomas, with significant differences in staining characteristics between the Lauren types in the absence of detectable MDM2 protein ( p< 0.005). Nearly 80 per cent of the carcinomas expressed p21(Waf1/Cip1), irrespective of Lauren type. Stratification of the carcinomas according to histological grade and growth pattern did not result in significant differences in p53 and p21(Waf1/Cip1) expression. Finally, no significant correlation was found between overall p53 and p21(Waf1/Cip1) expression in early gastric carcinomas. It is concluded that p21(Waf1/Cip1) expression in the non-neoplastic mucosa most likely relates to cell senescence and/or terminal differentiation, perhaps even in a p53-independent manner. In view of p53/MDM2 homeostasis, the differences in p53 staining characteristics between intestinal and diffuse-type carcinomas probably result, at least in part, from a difference in the prevalence of p53 gene mutations. Moreover, p53-independent induction of p21(Waf1/Cip1) expression apparently occurs in a considerable proportion of early carcinomas. Finally, in contrast to other carcinomas, p21(Waf1/Cip1) expression is not significantly correlated with histological grade in gastric carcinomas, suggesting possible defects downstream of p21(Waf1/Cip1) as an underlying cause for this apparent discrepancy.

Carcinoma↗

PubMed1999

Immunohistochemical differentiation between primary adenocarcinomas of the ovary and ovarian metastases of colonic and breast origin. Comparison between a statistical and an intuitive approach.

AIM: To discriminate between adenocarcinomas that are primary to the ovary and metastatic to the ovary, especially of colonic and breast origin, by immunohistochemistry, using stepwise discriminant analysis or a decision tree. METHODS: 312 routinely processed, formalin fixed tissue specimens were used. The tumours were divided into a learning set (n = 159), composed of primary tumours of ovary, breast, and colon, and a test set, comprising 134 metastases from these sites and an additional 19 primary ovarian carcinomas. The immunohistochemical panel was composed of antibodies against cytokeratin 7 (CK7) and 20 (CK20), CA125, vimentin, carcinoembryonic antigen (CEA), gross cystic disease fluid protein-15 (GCDFP-15), and the oestrogen receptor (ER). The staining results of the tumours were expressed as the product of the staining intensity and the percentage of positive tumour cells. Analyses were first performed on the learning set and then evaluated on the test set. RESULTS: Although the immunostaining patterns showed a considerable overlap between the three types of adenocarcinoma, the breast carcinomas were typically positive for GCDFP-15 and often for ER, and negative for vimentin. Ovarian carcinomas were always positive for CK7 and to a lesser extent for CA125. Colonic carcinomas showed prominent positivity for CEA and CK20, while no staining was seen for ER and vimentin. In discriminant analysis, six antibodies (alpha CK7, alpha CK20, alpha CA125, alpha CEA, alpha ER, and alpha GCDFP-15) appeared to be necessary for optimal classification: 89% of the learning set and 82% of the test set were classified correctly. In the decision tree, only four antibodies (alpha CK7, alpha CEA, alpha ER, and alpha GCDFP-15) were used to obtain a correct classification score of 89% for the learning set and 84% for the test set. CONCLUSIONS: Using a semiquantitative assessment of the immunostaining results by a restricted panel of six antibodies with stepwise discriminant analysis, 80-90% of the adenocarcinomas of colon, breast, and ovary can be correctly classified. Discriminant analysis is computer aided and therefore an easy method and for each case a probability value of the classification result is obtained. The intuitive decision tree method provides a slightly better result, requires only four antibodies, and offers a more practical method for the surgical pathologist.

Adenocarcinoma↗

PubMed1999

Increased expression of multidrug resistance related proteins Pgp, MRP1, and LRP/MVP occurs early in colorectal carcinogenesis.

AIM: To analyse the expression of multidrug resistance (MDR) related proteins at different steps in colorectal carcinogenesis. METHODS: The presence of three MDR related proteins (Pgp, MRP1, and LRP/MVP) was studied by means of immunohistochemistry in normal, adenomatous, and malignant colorectal epithelium. Formaldehyde fixed, paraffin embedded tissue sections of 17 samples of colorectal tissue were used (normal mucosa, n = 4; adjacent mucosa, n = 5; adenoma, n = 5; carcinoma, n = 3). RESULTS: For all three proteins, expression was found in the surface epithelium and the upper parts of the crypts in normal colon. In the adenomas, staining was seen along the complete length of the crypts. In the carcinomas analysed, all epithelium showed positive staining. Mucosa adjacent to either carcinoma or adenoma showed staining patterns mostly resembling those of normal mucosa, but sometimes some extension of staining was seen along the crypt. CONCLUSIONS: These proteins already show increased expression in the adenoma stage. In the absence of adequate mucin production in adenomas, MDR related proteins could be an important factor in protecting the epithelium against further environmentally induced genetic damage. This could be one of the reasons why only about 5% of colorectal adenomas will actually progress to carcinomas.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

Comparative genomic hybridisation.

Comparative genomic hybridisation (CGH) is a technique that permits the detection of chromosomal copy number changes without the need for cell culturing. It provides a global overview of chromosomal gains and losses throughout the whole genome of a tumour. Tumour DNA is labelled with a green fluorochrome, which is subsequently mixed (1:1) with red labelled normal DNA and hybridised to normal human metaphase preparations. The green and red labelled DNA fragments compete for hybridisation to their locus of origin on the chromosomes. The green to red fluorescence ratio measured along the chromosomal axis represents loss or gain of genetic material in the tumour at that specific locus. In addition to a fluorescence microscope, the technique requires a computer with dedicated image analysis software to perform the analysis. This review aims to provide a detailed discussion of the CGH technique, and to provide a protocol with an emphasis on crucial steps.

Chromosome Aberrations↗

PubMed1999

Hepatic fatty acid composition in periparturient dairy cows with fatty liver induced by intake of a high energy diet in the dry period.

The present study compared the hepatic fatty acid composition of cows that were fed a high energy diet during the dry period to induce fatty liver after parturition with that of control cows. Treated cows had higher concentrations of plasma nonesterified fatty acids as a result of greater lipolysis after parturition than did control cows; consequently, the treated cows accumulated greater amounts of triacylglycerols in the liver. Before parturition, treated cows had lower percentages of oleic acid and higher percentages of linoleic acid than did control cows, but percentages of other fatty acids were similar for both groups. After parturition, percentages of each fatty acid were changed substantially, particularly the four major fatty acids (palmitic, stearic, oleic, and linoleic acids). For treated cows, the percentages of palmitic and oleic acids were higher at 0.5 wk after parturition than at 1 wk before parturition; percentages of stearic and linoleic acids decreased. Unlike treated cows, the percentages of both oleic and linoleic acids in the control cows did not change during that time. Moreover, we found that when lipolysis decreased, as indicated by lower plasma nonesterified fatty acid concentrations, the percentages of each fatty acid gradually rebounded toward the concentrations measured before parturition; this observation indicates that the shift in hepatic fatty acid composition is influenced by lipolysis. The increased lipolysis after parturition led to a vast increase in the hepatic triacyglycerol concentration and to a shift in hepatic fatty acid composition.

3-Hydroxybutyric Acid↗

PubMed1999

Influence of section thickness, mean nuclear diameter and nuclear crowding on DNA ploidy in histologic sections of melanocytic skin lesions.

OBJECTIVE: To determine the influence of section thickness, nuclear diameter (MND) and area percentage of nuclei (a measure of nuclear crowding) on histologic DNA ploidy assessed by image cytometry (ICM) of primary melanocytic skin neoplasms (MSNs). STUDY DESIGN: Initially a feasibility study was performed to determine if comparable DNA ploidy histograms could be obtained from cell disaggregates and tissue sections. Following this, DNA ICM was performed on Feulgen-stained tissue sections (4, 6, 8 and 10 microns thick) from 30 primary MSNs (20 benign, 10 malignant) with nuclear diameters from 5.6 to 8.6 microns. Area percentage of nuclei was assessed in all cases at all section thicknesses. RESULTS: The feasibility study produced comparable results for cytocentrifuge and tissue section preparations. For sectioned MSNs, DNA ploidy histograms from 4-micron sections had a higher coefficient of variation of the 2c peak than those from 6-, 8- and 10-micron sections. Ten-micrometer sections had marked overlapping of nuclei, and only small numbers of cells could be measured, giving inadequate results. MND and area percentage of nuclei did not have an important influence on the results. CONCLUSION: Adequate DNA ploidy profiles can be obtained by DNA ICM on 6- and 8-micron-thick histologic sections of MSNs, provided that a strict measurement protocol is followed.

Cell Count↗

PubMed1999

DNA ploidy and nuclear morphometry for the classification of dysplastic nevi.

OBJECTIVE: To examine the diagnostic value of DNA ploidy and nuclear morphometric features in sporadic dysplastic nevi as compared to those in compound nevi and melanoma. STUDY DESIGN: DNA ploidy profiles plus seven direct and three derived nuclear features were obtained in a series of 120 melanocytic skin neoplasms (30 dysplastic nevi [DN], 30 melanomas [MM], 60 compound nevi [CN]) and the results compared. RESULTS: DNA ploidy separated melanomas from benign melanocytic skin neoplasms with 96.5% accuracy in classifying the grouped cases. The derived nuclear shape factor Form PE and nuclear axis ratio were the most successful discriminants separating DN from MM but allowed only 73.3% correct classification of cases. Separation of DN from CN was best achieved using Form PE and mean nuclear area (74.4% correctly classified). Results from compound nevi in subjects < 25 years of age fell between those for DN and MM. CONCLUSION: Quantitative nuclear cytologic characteristics in sporadic dysplastic nevi span a range seen in common nevi through to those in thin melanomas. Cytologic changes in sporadic dysplastic nevi overlap those seen in other melanocytic skin neoplasms. Therefore, other reproducible morphometric features need to be assessed in order to further refine the histopathologic diagnosis of this entity.

Adult↗

PubMed1998

Non-random allelic losses at 3p, 11p and 13q during HPV-mediated immortalization and concomitant loss of terminal differentiation of human keratinocytes.

To obtain a comprehensive overview of chromosomal alterations that may underlie human papillomavirus (HPV)-mediated immortalization, 4 foreskin keratinocyte cell lines generated by transfection with either HPV 16 (cell lines FK16A and FK16B) or HPV 18 (FK18A and FK18B) were subjected to chromosomal analysis using comparative genomic hybridization (CGH). Three cell lines were analyzed both in the mortal state during their extended lifespan and in the subsequent immortal state. From cell line FK18A, only immortal cells were tested. Chromosomal imbalances increased in number through the process of immortalization. Subsequent loss of heterozygosity (LOH) analysis, using a panel of 21 microsatellite markers selected on the basis of CGH losses, revealed no clonal LOHs in cells at the mortal stage. However, in the immortal descendants 67% of underrepresentations detected by CGH were expressed as clonal LOH at the respective loci. Clonal LOHs at 3p, 11p and 13q were detected in 2 cell lines each and were thus considered non-random. Immortal cells of 1 cell line (FK18B) revealed LOH at all 3 loci. Moreover, all immortal cell lines displaying allelic losses at one or more of these loci shared a severely dysplastic phenotype after organotypic culturing, as shown previously. Therefore, loss-of-function mutations of genes at these loci, eventually in combination, are potentially involved in the process of HPV-mediated immortalization that is attended by a loss of terminal differentiation. Since chromosomal changes at these loci are also found in HPV-associated carcinomas in vivo, the HPV-transfected cell lines seem to provide a valuable model system for studying HPV-mediated carcinogenesis.

Alleles↗

PubMed1998

Predicting the risk of metachronous colorectal cancer in patients with rectosigmoid adenoma using quantitative pathological features. A case-control study.

The prognostic value of quantitative pathological features in rectosigmoid adenomas was investigated, in search of more precise identifiers of adenoma-bearing patients at high risk of metachronous colorectal cancer. In a "nested case-control study" design, 21 cases with metachronous colon cancer during an average follow-up time of 16 years (range 3-30 years) after polypectomy and 67 controls were selected from a cohort of 1618 patients. The most advanced adenoma of each patient was analysed. Cases were matched with up to three controls simultaneously for size, grade of dysplasia, histological type, and number of adenomas, as well as for duration of follow-up. The patients did not undergo any post-polypectomy surveillance. Geometric characteristics of tumour nuclei, the arrangement of nuclei in the epithelium, and glandular changes were measured, and mitoses were counted. Several quantitative features measuring nuclear polymorphism and crowding showed significant prognostic value, while those measuring glandular changes and mitotic activity did not. A multivariate combination of the average distance between nuclei and the standard deviation of nuclear area discriminated an unfavourable group (n = 44) with 17 metachronous cancers from a favourable group (n = 44) with four metachronous cancers (P = 0*001, RR = 6*3). With the optimum cut-off, 28 patients without any metachronous cancer were discriminated from a group of 60 patients with 21 metachronous cancers. In conclusion, in the present study, quantitative pathological features assessed in rectosigmoid adenomas showed prognostic value additional to traditional measures. These features may therefore be useful in guiding post-polypectomy surveillance.

Adenoma↗

PubMed1998

Clinical decision making in Barrett's oesophagus can be supported by computerized immunoquantitation and morphometry of features associated with proliferation and differentiation.

Grading of dysplasia in Barrett's oesophagus has a therapeutic impact, but subjective grading is associated with substantial observer variation. Quantitative pathological methods could help to achieve a more accurate and reproducible diagnosis. In the present study, the immunoquantitation of p53 and Ki67 and the morphometric analysis of features associated with proliferation and differentiation were evaluated for this purpose. In slides of 35 oesophagectomy specimens, 73 areas that displayed either no dysplasia (ND), low-grade dysplasia (LGD), high-grade dysplasia (HGD), or intramucosal carcinoma (ImCa) were initially considered. Agreement on double blind examination by two experienced pathologists was reached in 58 areas, which were used as the 'learning set'. The 15 areas of disagreement were used as a second set. In the univariate analysis, the most significant differences in the learning set were found for Ki67, p53, stratification index (SI), mean nuclear area, and volume. Further multivariate analysis showed that for discrimination between ND and LGD, the combination of Ki67 and SI resulted in 94 per cent correctly classified areas. Likewise, for the discrimination between LGD and HGD, Ki67 and SI were the most powerful combination (again, 94 per cent of areas classified correctly). The discrimination between HGD and ImCa with any combination of the quantitative parameters never exceeded 80 per cent correct classification. The addition of p53 was of no value in improving the discrimination of ND vs. LGD, or of LGD vs. HGD. In the 15 original disagreement areas of the initial set of 73, three of the five ND/LGD areas could be uniquely classified as either ND or LGD by Ki67 and SI. Moreover, three of the four LGD/HGD disagreement areas could be uniquely classified with the combination of Ki67 and SI as either LGD or HGD. We conclude that the quantitative assessment of cytometric and morphometric features associated with proliferation and differentiation (especially Ki67 and SI) can be a valuable adjunct tool for clinical decision making in Barrett's oesophagus.

Barrett Esophagus↗

PubMed1998

Genetic analysis of 53 lymph node-negative breast carcinomas by CGH and relation to clinical, pathological, morphometric, and DNA cytometric prognostic factors.

Within the subgroup of lymph node-negative breast cancers, there is a need for accurate prognostic indicators to select high-risk patients. Comparative genomic hybridization (CGH) provides an opportunity to screen the whole genome for chromosomal aberrations which may be associated with poor clinical outcome. The results of CGH analysis of 53 lymph node-negative breast carcinomas are presented and correlated with a set of clinico-pathological and cytometric features with strong prognostic value. The most frequent chromosomal gains were, in descending order of frequency, 8q, 1q, Xq, 5q, 4q, and 3q. Recurring losses were observed at chromosomal arms 19p, 1p, 17p, 22q, 4q, and 8p. There was not a single, unique combination of chromosomal aberrations, but gains of 1q and 8q were frequently observed simultaneously (15/53 cases). DNA aneuploid tumours harboured more gains than DNA diploid tumours, but there was no correlation between the total number of events per tumour detected by CGH and any of the prognostic features. Of the many chromosomal aberrations found, only gains of chromosome 8q were strongly correlated with high values of mean nuclear area. A clearer picture was obtained when comparing only those cases which, according to their cytometric and morphometric features, had either the worst or the best prognosis. Gains occurred mainly in the 'poor prognostic features' group, in particular at 8q, 11q13, 17q, and 20q. It is hypothesized that these gains could be late, progression-related events and may be associated with aggressive clinical behaviour. These four chromosomal regions may therefore be of potential prognostic value. Correlation with real follow-up data will enable us better to identify those patients who have a high risk of recurrence within the subgroup of lymph node-negative breast cancer patients.

Adult↗

PubMed1998

Quantitative prognostic features in FIGO I ovarian cancer patients without postoperative treatment.

To identify FIGO I ovarian cancer patients at high risk, prognostic values of quantitative pathological features (volume percentage of epithelium, mitotic activity index, mean (MNA) and standard deviation of nuclear profile area, and volume-weighted mean nuclear volume (MNV) have been investigated in comparison with clinical features, histological grade, and type in 102 adequately staged patients with FIGO Ia, Ib, and Ic ovarian cancer of the common epithelial types. None of these patients received any postoperative treatment. Overall survival of patients alive and well was 78%, and 90% were alive. Of the clinical features, FIGO substage was the strongest prognosticator (Mantel-Cox = 7.2, p = 0.03, hazard ratio (HR) = 4.6). Histologic grade had significant prognostic value as well (Mantel-Cox = 9.7, p = 0.008, HR = 5.9), but histologic type did not. MNA and MNV were the strongest single prognostic factors for overall survival (Mantel-Cox = 12.3 for both; p = 0.0004 and 0. 0005). If MNA </= 55.6 micron2, none of the patients (n = 52) died; if MNA >55.6 micron2, 6-year overall survival was 69%. For MNV </=460 micron2, none of the patients (n = 53) died; if MNV >460 micron2, 6-year overall survival was 70%. A multivariate combination of MNA and FIGO (early cancer of the ovary prognostic score, ECOPS) had the strongest prognostic value (p < 0.0001 and Mantel-Cox value = 22.8, HR = 29.2). If ECOPS </= 5.4 (n = 66), 6-year overall survival was 97%; if ECOPS >5.4 (n = 36), 6-year overall survival was 54%. The results from this and earlier studies emphasize the strong prognostic value of easy to assess and highly reproducible morphometric nuclear features in ovarian tumors and offer a useful instrument for the definition of patient groups for future clinical trials.

Adolescent↗