M. Heiskanen, J. Kononen, M. Bärlund, J. Torhorst, G. Sauter, A. Kallioniemi, O. Kallioniemi
Multiple regions of the genome are often amplified during breast cancer development and progression, as evidenced in a number of published studies by comparative genomic hybridization (CGH). However, only relatively few target genes for such amplifications have been identified. Here, we indicate how small‐scale commercially available cDNA and CGH microarray formats combined with the tissue microarray technology enable rapid identification of putative amplification target genes as well as analysis of their clinical significance. According to CGH, the SUM‐52 breast cancer cell line harbors several high‐level DNA amplification sites, including the 10q26 chromosomal region where the fibroblast growth factor receptor 2 (FGFR2) gene has been localized. High level amplification of FGFR2 in SUM‐52 was identified using CGH analysis on a microarray of BAC clones. A cDNA microarray survey of 588 genes showed >40‐fold overexpression of FGFR2. Finally, a tissue microarray based FISH analysis of 750 uncultured primary breast cancers demonstrated in vivo amplification of the FGFR2 gene in about 1% of the tumors. In conclusion, three consecutive microarray (CGH, cDNA and tissue) experiments revealed high‐level amplification and overexpression of the FGFR2 in a breast cancer cell line, but only a low frequency of involvement in primary breast tumors. Applied to a genomic scale with larger arrays, this strategy should facilitate identification of the most important target genes for cytogenetic rearrangements, such as DNA amplification sites detected by conventional CGH. Figures on http://www.esacp.org/acp/2001/22‐4/heiskanen.htm
{"title":"CGH, cDNA and Tissue Microarray Analyses Implicate FGFR2 Amplification in a Small Subset of Breast Tumors","authors":"M. Heiskanen, J. Kononen, M. Bärlund, J. Torhorst, G. Sauter, A. Kallioniemi, O. Kallioniemi","doi":"10.1155/2001/981218","DOIUrl":"https://doi.org/10.1155/2001/981218","url":null,"abstract":"Multiple regions of the genome are often amplified during breast cancer development and progression, as evidenced in a number of published studies by comparative genomic hybridization (CGH). However, only relatively few target genes for such amplifications have been identified. Here, we indicate how small‐scale commercially available cDNA and CGH microarray formats combined with the tissue microarray technology enable rapid identification of putative amplification target genes as well as analysis of their clinical significance. According to CGH, the SUM‐52 breast cancer cell line harbors several high‐level DNA amplification sites, including the 10q26 chromosomal region where the fibroblast growth factor receptor 2 (FGFR2) gene has been localized. High level amplification of FGFR2 in SUM‐52 was identified using CGH analysis on a microarray of BAC clones. A cDNA microarray survey of 588 genes showed >40‐fold overexpression of FGFR2. Finally, a tissue microarray based FISH analysis of 750 uncultured primary breast cancers demonstrated in vivo amplification of the FGFR2 gene in about 1% of the tumors. In conclusion, three consecutive microarray (CGH, cDNA and tissue) experiments revealed high‐level amplification and overexpression of the FGFR2 in a breast cancer cell line, but only a low frequency of involvement in primary breast tumors. Applied to a genomic scale with larger arrays, this strategy should facilitate identification of the most important target genes for cytogenetic rearrangements, such as DNA amplification sites detected by conventional CGH. Figures on http://www.esacp.org/acp/2001/22‐4/heiskanen.htm","PeriodicalId":76996,"journal":{"name":"Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology","volume":"9 1","pages":"229 - 234"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77971967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. Blegen, B. Ghadimi, A. Jauho, A. Zetterberg, E. Eriksson, G. Auer, T. Ried
In order to evaluate biological and genetic properties of early breast carcinomas we analyzed microdissected tissue from 33 primary breast carcinomas stage T1b and T1c with respect to the nuclear DNA content, the expression pattern of Ki‐67, cyclin A, p27KIP1, p53 and p21WAF1, and chromosomal gains and losses. The results show that T1b carcinomas (6–10 mm, n=17) were frequently near‐diploid (53%) with low proliferative activity and staining patterns of p53 and p21WAF1 that suggest the presence of wild type protein. The majority (12/16) of the T1c tumors (11–20 mm), however, was aneuploid, and proliferative activity and p53 expression were increased. Larger tumor size correlated with an increasing number of chromosomal copy number changes and in particular with regional amplifications. High level copy number increases (amplifications), however, were found exclusively in the aneuploid tumors. Amplification events correlated with elevated cyclin A and reduced p27 expression, respectively. Our results suggest that the sequential acquisition of genomic imbalances during tumor progression is accelerated in aneuploid tumors, and may contribute to the increased malignancy potential.
为了评估早期乳腺癌的生物学和遗传学特性，我们分析了33例T1b和T1c期原发性乳腺癌的微解剖组织，包括核DNA含量、Ki‐67、细胞周期蛋白A、p27KIP1、p53和p21WAF1的表达模式以及染色体的获得和损失。结果显示，T1b癌(6-10 mm, n=17)通常为近二倍体(53%)，增殖活性低，p53和p21WAF1的染色模式表明存在野生型蛋白。然而，大多数(12/16)T1c肿瘤(11 - 20mm)为非整倍体，增殖活性和p53表达增加。较大的肿瘤大小与染色体拷贝数变化的增加有关，特别是与区域扩增有关。然而，高水平的拷贝数增加(扩增)仅在非整倍体肿瘤中发现。扩增事件分别与细胞周期蛋白A升高和p27表达降低相关。我们的研究结果表明，在非整倍体肿瘤中，肿瘤进展过程中基因组失衡的顺序获得加速，并可能导致恶性肿瘤的可能性增加。
{"title":"Genetic Instability Promotes the Acquisition of Chromosomal Imbalances in T1b and T1c Breast Adenocarcinomas","authors":"H. Blegen, B. Ghadimi, A. Jauho, A. Zetterberg, E. Eriksson, G. Auer, T. Ried","doi":"10.1155/2001/126030","DOIUrl":"https://doi.org/10.1155/2001/126030","url":null,"abstract":"In order to evaluate biological and genetic properties of early breast carcinomas we analyzed microdissected tissue from 33 primary breast carcinomas stage T1b and T1c with respect to the nuclear DNA content, the expression pattern of Ki‐67, cyclin A, p27KIP1, p53 and p21WAF1, and chromosomal gains and losses. The results show that T1b carcinomas (6–10 mm, n=17) were frequently near‐diploid (53%) with low proliferative activity and staining patterns of p53 and p21WAF1 that suggest the presence of wild type protein. The majority (12/16) of the T1c tumors (11–20 mm), however, was aneuploid, and proliferative activity and p53 expression were increased. Larger tumor size correlated with an increasing number of chromosomal copy number changes and in particular with regional amplifications. High level copy number increases (amplifications), however, were found exclusively in the aneuploid tumors. Amplification events correlated with elevated cyclin A and reduced p27 expression, respectively. Our results suggest that the sequential acquisition of genomic imbalances during tumor progression is accelerated in aneuploid tumors, and may contribute to the increased malignancy potential.","PeriodicalId":76996,"journal":{"name":"Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology","volume":"49 1","pages":"123 - 131"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81790943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B. Planz, C. Synek, T. Deix, A. Böcking, M. Marberger
DNA‐image‐cytometry and antibodies directed against the Lewis X‐ and the 486p 3/12 antigen were applied to improve diagnostic accuracy of urinary cytology for the detection of bladder cancer. Cytology, immunocytology and DNA‐image‐cytometry were performed in spontaneously voided urine samples and barbotage bladder washings from 71 patients. The DNA content was determined using the CM‐1 Cytometer according to the recommendation of the ESCAP Consensus Report on Standardization of DNA‐image‐cytometry (1995). For immunocytological examination we used the monoclonal anti Lewis X antibody P‐12 and antibody 486p 3/12. All patients underwent subsequent cystoscopy and for any suspicious lesion biopsy or transurethral resection was done. Histological findings revealed 31 patients with transitional cell carcinomas of different stages and grades of malignancy. 40 patients had various benign diseases of the urinary bladder. Cytology yielded a sensitivity of 68% and a specificity of 100%. DNA aneuploidy was detected in 81% of cancer patients with a specificity of 100%. By combination of these two methods the overall sensitivity increased to 87%. Immunocytology with Lewis X and 486p 3/12 antibodies showed reactivity in 84% and 87% in combination with a specificity of 80% and 70%, respectively. By combining urinary cytology, immunocytology and/or DNA‐image‐cytometry the overall sensitivity increased to 94% with no change in specificity. DNA‐image‐cytometry should be used to evaluate particularly urothelial cells suspicious for malignancy in urinary specimens. Because of low specificity the monoclonal antibodies against Lewis X‐ and 486p 3/12 antigens are not helpful in screening for bladder cancer. Nevertheless, their high sensitivity may justify their use in case DNA image cytometry is not available and in the follow up of patients with transitional cell carcinoma.
{"title":"Diagnosis of Bladder Cancer with Urinary Cytology, Immunocytology and DNA-Image-Cytometry1","authors":"B. Planz, C. Synek, T. Deix, A. Böcking, M. Marberger","doi":"10.1155/2001/703731","DOIUrl":"https://doi.org/10.1155/2001/703731","url":null,"abstract":"DNA‐image‐cytometry and antibodies directed against the Lewis X‐ and the 486p 3/12 antigen were applied to improve diagnostic accuracy of urinary cytology for the detection of bladder cancer. Cytology, immunocytology and DNA‐image‐cytometry were performed in spontaneously voided urine samples and barbotage bladder washings from 71 patients. The DNA content was determined using the CM‐1 Cytometer according to the recommendation of the ESCAP Consensus Report on Standardization of DNA‐image‐cytometry (1995). For immunocytological examination we used the monoclonal anti Lewis X antibody P‐12 and antibody 486p 3/12. All patients underwent subsequent cystoscopy and for any suspicious lesion biopsy or transurethral resection was done. Histological findings revealed 31 patients with transitional cell carcinomas of different stages and grades of malignancy. 40 patients had various benign diseases of the urinary bladder. Cytology yielded a sensitivity of 68% and a specificity of 100%. DNA aneuploidy was detected in 81% of cancer patients with a specificity of 100%. By combination of these two methods the overall sensitivity increased to 87%. Immunocytology with Lewis X and 486p 3/12 antibodies showed reactivity in 84% and 87% in combination with a specificity of 80% and 70%, respectively. By combining urinary cytology, immunocytology and/or DNA‐image‐cytometry the overall sensitivity increased to 94% with no change in specificity. DNA‐image‐cytometry should be used to evaluate particularly urothelial cells suspicious for malignancy in urinary specimens. Because of low specificity the monoclonal antibodies against Lewis X‐ and 486p 3/12 antigens are not helpful in screening for bladder cancer. Nevertheless, their high sensitivity may justify their use in case DNA image cytometry is not available and in the follow up of patients with transitional cell carcinoma.","PeriodicalId":76996,"journal":{"name":"Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology","volume":"13 1","pages":"103 - 109"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85877036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: To evaluate the feasibility of the CART (Classification and Regression Tree) procedure for the recognition of microscopic structures in tissue counter analysis. Methods: Digital microscopic images of H&E stained slides of normal human skin and of primary malignant melanoma were overlayed with regularly distributed square measuring masks (elements) and grey value, texture and colour features within each mask were recorded. In the learning set, elements were interactively labeled as representing either connective tissue of the reticular dermis, other tissue components or background. Subsequently, CART models were based on these data sets. Results: Implementation of the CART classification rules into the image analysis program showed that in an independent test set 94.1% of elements classified as connective tissue of the reticular dermis were correctly labeled. Automated measurements of the total amount of tissue and of the amount of connective tissue within a slide showed high reproducibility (r=0.97 and r=0.94, respectively; p < 0.001). Conclusions: CART procedure in tissue counter analysis yields simple and reproducible classification rules for tissue elements.
{"title":"Automated Detection of Connective Tissue by Tissue Counter Analysis and Classification and Regression Trees","authors":"J. Smolle, P. Kahofer","doi":"10.1155/2001/626382","DOIUrl":"https://doi.org/10.1155/2001/626382","url":null,"abstract":"Objective: To evaluate the feasibility of the CART (Classification and Regression Tree) procedure for the recognition of microscopic structures in tissue counter analysis. Methods: Digital microscopic images of H&E stained slides of normal human skin and of primary malignant melanoma were overlayed with regularly distributed square measuring masks (elements) and grey value, texture and colour features within each mask were recorded. In the learning set, elements were interactively labeled as representing either connective tissue of the reticular dermis, other tissue components or background. Subsequently, CART models were based on these data sets. Results: Implementation of the CART classification rules into the image analysis program showed that in an independent test set 94.1% of elements classified as connective tissue of the reticular dermis were correctly labeled. Automated measurements of the total amount of tissue and of the amount of connective tissue within a slide showed high reproducibility (r=0.97 and r=0.94, respectively; p < 0.001). Conclusions: CART procedure in tissue counter analysis yields simple and reproducible classification rules for tissue elements.","PeriodicalId":76996,"journal":{"name":"Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology","volume":"28 1","pages":"153 - 158"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80103295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Naining Wang, Qimin He, S. Skog, S. Eriksson, B. Tribukait
The cytosolic thymidine kinase 1 (TK1) is one of the enzymes involved in DNA replication. Based on biochemical studies, TK1 is activated at late G1 of cell cycle, and its activity correlates with the cell proliferation. We have developed a polyclonal anti‐TK1 antibody against a synthetic peptide from the C‐terminus of human TK1. Using this antibody, here we demonstrate the exclusive location of TK1 in the cytoplasm of cells. Cell cycle dependent TK1 expression was studied by simultaneous fluorescence staining for TK1 and bromodeoxyuridine, by using elutriated cells, and by quantitation of the amount TK1 in relation to the cellular DNA content. TK1, which was strongly expressed in the cells in S+G2 period, raised at late G1 and decreased during mitosis. The amount of TK1 increased three folds from late G1 to G2. TK1 positive cells were demonstrated in areas of proliferation activity of various normal and malignant tissues. The new anti‐TK1 antibody works in archival specimens and is a specific marker of cell proliferation.
{"title":"Investigation on Cell Proliferation with a New Antibody against Thymidine Kinase 1","authors":"Naining Wang, Qimin He, S. Skog, S. Eriksson, B. Tribukait","doi":"10.1155/2001/658312","DOIUrl":"https://doi.org/10.1155/2001/658312","url":null,"abstract":"The cytosolic thymidine kinase 1 (TK1) is one of the enzymes involved in DNA replication. Based on biochemical studies, TK1 is activated at late G1 of cell cycle, and its activity correlates with the cell proliferation. We have developed a polyclonal anti‐TK1 antibody against a synthetic peptide from the C‐terminus of human TK1. Using this antibody, here we demonstrate the exclusive location of TK1 in the cytoplasm of cells. Cell cycle dependent TK1 expression was studied by simultaneous fluorescence staining for TK1 and bromodeoxyuridine, by using elutriated cells, and by quantitation of the amount TK1 in relation to the cellular DNA content. TK1, which was strongly expressed in the cells in S+G2 period, raised at late G1 and decreased during mitosis. The amount of TK1 increased three folds from late G1 to G2. TK1 positive cells were demonstrated in areas of proliferation activity of various normal and malignant tissues. The new anti‐TK1 antibody works in archival specimens and is a specific marker of cell proliferation.","PeriodicalId":76996,"journal":{"name":"Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology","volume":"30 1","pages":"11 - 19"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77644346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lung cancer is a highly aggressive neoplasm which is reflected by a multitude of genetic aberrations being detectable on the chromosomal and molecular level. In order to understand this seemingly genetic chaos, we performed Comparative Genomic Hybridisation (CGH) in a large collective of human lung carcinomas investigating different tumor entities as well as multiple individual tumour specimens of single patients. Despite the considerable genetic instability being reflected by the well known morphological heterogeneity of lung cancer the comparison of different tumour groups using custom made computer software revealed recurrent aberration patterns and highlighted chromosomal imbalances that were significantly associated with morphological histotypes and biological phenotypes. Specifically we identified imbalances in NSCLC being associated with metastasis formation which are typically present in SCLC thus explaining why the latter is such an aggressive neoplasm characterized by widespread tumor dissemination. Based on the genetic data a new model for the development of SCLC is presented. It suggests that SCLC evolving from the same stem cell as NSCLC should be differentiated into primary and secondary tumors. Primary SCLC corresponding to the classical type evolved directly from an epithelial precursor cell. In contrast, secondary SCLC correlating with the combined SCLC develops via an NSCLC intermediate. In addition, we established libraries of differentially expressed genes from different human lung cancer types to identify new candidate genes for several of the chromosomal subregions identified by CGH. In this review, we summarise the status of our results aiming at a refined classification of lung cancer based on the pattern of genetic aberrations.
{"title":"Towards a Genetic-Based Classification of Human Lung Cancer","authors":"I. Petersen, S. Petersen","doi":"10.1155/2001/374304","DOIUrl":"https://doi.org/10.1155/2001/374304","url":null,"abstract":"Lung cancer is a highly aggressive neoplasm which is reflected by a multitude of genetic aberrations being detectable on the chromosomal and molecular level. In order to understand this seemingly genetic chaos, we performed Comparative Genomic Hybridisation (CGH) in a large collective of human lung carcinomas investigating different tumor entities as well as multiple individual tumour specimens of single patients. Despite the considerable genetic instability being reflected by the well known morphological heterogeneity of lung cancer the comparison of different tumour groups using custom made computer software revealed recurrent aberration patterns and highlighted chromosomal imbalances that were significantly associated with morphological histotypes and biological phenotypes. Specifically we identified imbalances in NSCLC being associated with metastasis formation which are typically present in SCLC thus explaining why the latter is such an aggressive neoplasm characterized by widespread tumor dissemination. Based on the genetic data a new model for the development of SCLC is presented. It suggests that SCLC evolving from the same stem cell as NSCLC should be differentiated into primary and secondary tumors. Primary SCLC corresponding to the classical type evolved directly from an epithelial precursor cell. In contrast, secondary SCLC correlating with the combined SCLC develops via an NSCLC intermediate. In addition, we established libraries of differentially expressed genes from different human lung cancer types to identify new candidate genes for several of the chromosomal subregions identified by CGH. In this review, we summarise the status of our results aiming at a refined classification of lung cancer based on the pattern of genetic aberrations.","PeriodicalId":76996,"journal":{"name":"Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology","volume":"8 1","pages":"111 - 121"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73834764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: We have previously demonstrated that the AgNOR count in proliferating cells is a predictor of tumor recurrence in superficial bladder tumor (J. Urol. 162 (1999), 63–68). In the present study, we evaluate the type of AgNOR associated with cell cycles as a prognostic factor in invasive bladder tumor using a double staining technique employing both AgNOR and MIB-1 labelling. Materials and methods: Forty-four paraffin sections of invasive bladder tumors were stained simultaneously with AgNOR and MIB-1. The number of AgNORs in proliferating (MIB-1 positive) or resting (MIB-1 negative) cells were counted from a total of 100 nuclei. Correlations between MIB-1 associated AgNOR count and clinicopathological parameters were statistically analyzed. Results: The AgNOR count in proliferating cells (proliferating NOR) was significantly higher than that in resting cells (resting NOR) (p < 0.01). The resting NOR in tumors with distant metastases was significantly higher than that in tumors without metastases (p < 0.05). Patients with a low resting NOR tumor had a better prognosis than those with a high resting NOR tumor, whereas the proliferating NOR was not associated with survival. Survival analysis revealed that the resting NOR was the most powerful prognostic marker in patients with invasive bladder tumor (p < 0.05). Conclusions: Resting NOR had a predictive value in the prognosis of patients with invasive bladder tumor. Keywords: Transitional cell carcinoma, invasive, resting cell, AgNORs, MIB-1
{"title":"AgNOR Count in Resting Cells (Resting NOR) Is a New Prognostic Marker in Invasive Bladder Tumor","authors":"M. Tomobe, T. Shimazui, K. Uchida, H. Akaza","doi":"10.1155/2001/689480","DOIUrl":"https://doi.org/10.1155/2001/689480","url":null,"abstract":"Purpose: We have previously demonstrated that the AgNOR count in proliferating cells is a predictor of tumor recurrence in superficial bladder tumor (J. Urol. 162 (1999), 63–68). In the present study, we evaluate the type of AgNOR associated with cell cycles as a prognostic factor in invasive bladder tumor using a double staining technique employing both AgNOR and MIB-1 labelling. Materials and methods: Forty-four paraffin sections of invasive bladder tumors were stained simultaneously with AgNOR and MIB-1. The number of AgNORs in proliferating (MIB-1 positive) or resting (MIB-1 negative) cells were counted from a total of 100 nuclei. Correlations between MIB-1 associated AgNOR count and clinicopathological parameters were statistically analyzed. Results: The AgNOR count in proliferating cells (proliferating NOR) was significantly higher than that in resting cells (resting NOR) (p < 0.01). The resting NOR in tumors with distant metastases was significantly higher than that in tumors without metastases (p < 0.05). Patients with a low resting NOR tumor had a better prognosis than those with a high resting NOR tumor, whereas the proliferating NOR was not associated with survival. Survival analysis revealed that the resting NOR was the most powerful prognostic marker in patients with invasive bladder tumor (p < 0.05). Conclusions: Resting NOR had a predictive value in the prognosis of patients with invasive bladder tumor. Keywords: Transitional cell carcinoma, invasive, resting cell, AgNORs, MIB-1","PeriodicalId":76996,"journal":{"name":"Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology","volume":"104 1","pages":"193 - 199"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85785028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Arnerlöv, S. Emdin, S. Cajander, N. Bengtsson, B. Tavelin, G. Roos
To study intratumoral DNA ploidy heterogeneity and S‐phase fraction (SPF) variability, we prospectively collected five different samples from 48 breast carcinomas and each sample was analysed separately by flow cytometry. Aneuploidy rate was 89.6% after analysis of four or five samples. DNA ploidy heterogeneity, i.e., different samples classified as either DNA euploid or DNA aneuploid in the same tumor was seen in 17%, and DNA index heterogeneity, i.e., tumor populations with different DNA indices (DIs) seen in different samples was 44%. A statistical model defining SPF heterogeneity is proposed. SPF heterogeneity as defined by us was 71%, and as expected the SPF heterogeneity rate increased significantly with increasing number of analysed samples. Four or more samples are needed to detect the most deviant (highest) SPF values. An unrecognized intratumor heterogeneity of DNA ploidy and SPF may partly explain the conflicting results reported in the literature on the above prognostic indicators.
{"title":"Intratumoral Variations in DNA Ploidy and S-Phase Fraction in Human Breast Cancer","authors":"C. Arnerlöv, S. Emdin, S. Cajander, N. Bengtsson, B. Tavelin, G. Roos","doi":"10.1155/2001/430674","DOIUrl":"https://doi.org/10.1155/2001/430674","url":null,"abstract":"To study intratumoral DNA ploidy heterogeneity and S‐phase fraction (SPF) variability, we prospectively collected five different samples from 48 breast carcinomas and each sample was analysed separately by flow cytometry. Aneuploidy rate was 89.6% after analysis of four or five samples. DNA ploidy heterogeneity, i.e., different samples classified as either DNA euploid or DNA aneuploid in the same tumor was seen in 17%, and DNA index heterogeneity, i.e., tumor populations with different DNA indices (DIs) seen in different samples was 44%. A statistical model defining SPF heterogeneity is proposed. SPF heterogeneity as defined by us was 71%, and as expected the SPF heterogeneity rate increased significantly with increasing number of analysed samples. Four or more samples are needed to detect the most deviant (highest) SPF values. An unrecognized intratumor heterogeneity of DNA ploidy and SPF may partly explain the conflicting results reported in the literature on the above prognostic indicators.","PeriodicalId":76996,"journal":{"name":"Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology","volume":"83 1","pages":"21 - 28"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75253606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives. When analysing the 3D structure of tissue, serial sectioning and staining of the resulting slices is sometimes the preferred option. This leads to severe registration problems. In this paper, a method for automatic registration and error detection of slices using landmark needles has been developed. A cost function takes some parameters from the current state of the problem to be solved as input and gives a quality of the current solution as output. The cost function used in this paper, is based on a model of the slices and the landmark needles. The method has been used to register slices of prostates in order to create 3D computer models. Manual registration of the same prostates has been undertaken and compared with the results from the algorithm. Methods. Prostates from sixteen men who underwent radical prostatectomy were formalin fixed with landmark needles, sliced and the slices were computer reconstructed. The cost function takes rotation and translation for each prostate slice, as well as slope and offset for each landmark needle as input. The current quality of fit of the model, using the input parameters given, is returned. The function takes the built‐in instability of the model into account. The method uses a standard algorithm to optimize the prostate slice positions. To verify the result, s standard method in statistics was used. Results. The methods were evaluated for 16 prostates. When testing blindly, a physician could not determine whether the registration shown to him were created by the automated method described in this paper, or manually by an expert, except in one out of 16 cases. Visual inspection and analysis of the outlier confirmed that the input data had been deformed. The automatic detection of erroneous slices marked a few slices, including the outlier, as suspicious. Conclusions. The model based registration performs better than traditional simple slice‐wise registration. In the case of prostate slice registration, other aspects, such as the physical slicing method used, may be more important to the final result than the selection of registration method to use.
{"title":"Automatic Registration and Error Detection of Multiple Slices Using Landmarks","authors":"H. Frimmel, L. Egevad, C. Busch, E. Bengtsson","doi":"10.1155/2001/367976","DOIUrl":"https://doi.org/10.1155/2001/367976","url":null,"abstract":"Objectives. When analysing the 3D structure of tissue, serial sectioning and staining of the resulting slices is sometimes the preferred option. This leads to severe registration problems. In this paper, a method for automatic registration and error detection of slices using landmark needles has been developed. A cost function takes some parameters from the current state of the problem to be solved as input and gives a quality of the current solution as output. The cost function used in this paper, is based on a model of the slices and the landmark needles. The method has been used to register slices of prostates in order to create 3D computer models. Manual registration of the same prostates has been undertaken and compared with the results from the algorithm. Methods. Prostates from sixteen men who underwent radical prostatectomy were formalin fixed with landmark needles, sliced and the slices were computer reconstructed. The cost function takes rotation and translation for each prostate slice, as well as slope and offset for each landmark needle as input. The current quality of fit of the model, using the input parameters given, is returned. The function takes the built‐in instability of the model into account. The method uses a standard algorithm to optimize the prostate slice positions. To verify the result, s standard method in statistics was used. Results. The methods were evaluated for 16 prostates. When testing blindly, a physician could not determine whether the registration shown to him were created by the automated method described in this paper, or manually by an expert, except in one out of 16 cases. Visual inspection and analysis of the outlier confirmed that the input data had been deformed. The automatic detection of erroneous slices marked a few slices, including the outlier, as suspicious. Conclusions. The model based registration performs better than traditional simple slice‐wise registration. In the case of prostate slice registration, other aspects, such as the physical slicing method used, may be more important to the final result than the selection of registration method to use.","PeriodicalId":76996,"journal":{"name":"Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology","volume":"60 1","pages":"159 - 165"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84473861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
RNA relocation and the incidence of nucleolus‐like bodies accumulated during mitosis were studied cytochemically in benzo[a]pyrene (BP)‐transformed human breast epithelial MCF‐10F cells after microcell‐mediated transfer of normal chromosomes 11 and 17. The changes resulting from the transfer of these two chromosomes in tumorigenic MCF‐10F cells (BP1‐E cell line) were examined, since alterations in these chromosomes are involved in the expression of the transformed and tumorigenic phenotypes in the MCF‐10F cell series. In addition, the frequency of nucleolus‐like bodies decreases drastically with transformation and tumorigenicity in MCF‐10F cells, thus being conceivable that it would be affected in presence of normal chromosomes 11 or 17. The pattern of RNA relocation associated with the mitotic spindle did not vary in the cell lines analyzed. The introduction of chromosome 17 in BP1‐E cells either decreased or did not affect the frequency of persistent nucleolus‐like bodies. In contrast, in cells which received a normal chromosome 11, the frequency of nucleolus‐like bodies was closer to that of non‐transformed MCF‐10F cells. These results suggest that a normal chromosome 11 but not chromosome 17 contributes to the maintenance of an RNA surplus which accumulates in nucleolus‐like bodies during cell division of the human breast epithelial cells, at least in vitro. Some loci which were retained in the BP1‐E cells which received a normal chromosome 11 are probably involved with the control of RNA transcript production.
{"title":"RNA Relocation and Persistence of Nucleolus-Like Bodies at Mitosis in Benzo[a]Pyrene-Transformed Human Breast Epithelial Cells after Microcell-Mediated Transfer of Chromosomes 11 and 17","authors":"M. Mello, M. Lareef, B. Vidal, J. Russo","doi":"10.1155/2001/630121","DOIUrl":"https://doi.org/10.1155/2001/630121","url":null,"abstract":"RNA relocation and the incidence of nucleolus‐like bodies accumulated during mitosis were studied cytochemically in benzo[a]pyrene (BP)‐transformed human breast epithelial MCF‐10F cells after microcell‐mediated transfer of normal chromosomes 11 and 17. The changes resulting from the transfer of these two chromosomes in tumorigenic MCF‐10F cells (BP1‐E cell line) were examined, since alterations in these chromosomes are involved in the expression of the transformed and tumorigenic phenotypes in the MCF‐10F cell series. In addition, the frequency of nucleolus‐like bodies decreases drastically with transformation and tumorigenicity in MCF‐10F cells, thus being conceivable that it would be affected in presence of normal chromosomes 11 or 17. The pattern of RNA relocation associated with the mitotic spindle did not vary in the cell lines analyzed. The introduction of chromosome 17 in BP1‐E cells either decreased or did not affect the frequency of persistent nucleolus‐like bodies. In contrast, in cells which received a normal chromosome 11, the frequency of nucleolus‐like bodies was closer to that of non‐transformed MCF‐10F cells. These results suggest that a normal chromosome 11 but not chromosome 17 contributes to the maintenance of an RNA surplus which accumulates in nucleolus‐like bodies during cell division of the human breast epithelial cells, at least in vitro. Some loci which were retained in the BP1‐E cells which received a normal chromosome 11 are probably involved with the control of RNA transcript production.","PeriodicalId":76996,"journal":{"name":"Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology","volume":"22 1","pages":"137 - 141"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75995678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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