Analytical Cellular Pathology - Volume 27, issue 1

Authors: Baumgart, Mario | Heinmöller, Ernst | Horstmann, Olaf | Becker, Heinz | Ghadimi, B. Michael

Article Type: Other

Citation: Analytical Cellular Pathology, vol. 27, no. 1, pp. 3-13, 2005

Authors: de Visser, M. | van Ballegooijen, M. | Bloemers, S.M. | van Deventer, S.J.H. | Jansen, J.B.M.J. | Jespersen, J. | Kluft, C. | Meijer, G.A. | Stoker, J. | de Valk, G.A. | Verweij, M.F. | Vlems, F.A.

Article Type: Other

Abstract: A consensus development meeting was held to evaluate whether or not in the Netherlands all requirements were fulfilled for implementation of population screening with FOBT for colorectal cancer, or whether consensus was present that fulfilment by additional research or organisational actions could be obtained within 2–3 years. There was consensus that all classical Wilson and Jungner (1968) criteria, and six additional ones added more recently, had already been fulfilled or could be fulfilled within 2–3 years. Consequently, it was concluded that a national population screening for colorectal cancer should be implemented and carried out in the Netherlands in line with …current national and European cancer screening programmes. A list of organisational actions to be taken was established. Research that is needed before the actual national launch of the screening within 2–3 years has been defined. Priorities have to be set for research and organisational actions for the coming 2–3 years for the implementation of population screening. In addition, research suggestions have been defined for the next 10–15 years for evaluation and/or improvement of implemented FOBT screening, and for future screening methodology. It was considered essential that infrastructure for future research would be embedded in the screening programme. A project group to arrange this should be formed. Show more

Keywords: Colorectal cancer, adenoma, screening, FOBT, consensus

Citation: Analytical Cellular Pathology, vol. 27, no. 1, pp. 17-29, 2005

Authors: Sun, Xiao Rong | Wang, Jian | Garner, David | Palcic, Branko

Article Type: Research Article

Abstract: Objective: To establish if measurements of DNA ploidy could be used to assist cytopathologists and cytotechnologists in population based cervical cancer screening programs in countries where manually reading the slides is impossible due to the lack of sufficient skilled cytotechnologists. The goal of such program is to identify only clinically significant lesions, i.e. those where a clinical intervention to remove the lesion is required immediately. Study design: A total of 9905 women were enrolled in the study. Cervical samples were taken with a cervix brush that was then placed into a fixative solution. The cells were separated from mucus by …mechanical and chemical treatment and then deposited onto microscope slides by a cytocentrifuge. Two slides were prepared from each case; one slide was stained by Papanicolaou stain for manual cytology examination, while the other slide was stained by a DNA specific stain. The latter slide was used to determine the relative amount of DNA in the cell nuclei. Results: A total of 876 women were followed by colposcopy examination where biopsies were taken from the visible lesions or from suspicious areas and histopathology diagnosed 459 as normal or benign cases, 325 as CIN1, 36 as CIN2, 25 as CIN3/CIS, and 31 as invasive cancer. Of these 876 cases, manual cytology called 655 normal or ASCUS, 197 as LSIL, 16 cases as HSIL, and 8 as cancer. DNA measurements found 704 cases having no cells with DNA greater than 5c, 98 cases where there were 1 or 2 cells having DNA amount greater than 5c, and 74 cases where there were 3 or more cells having DNA amount greater than 5c. If manual cytology were to be used to refer all cases of HSIL and cancer to colposcopy and biopsy, 23 lesions that had to be removed would have been discovered (2 CIN2, 11 CIN3/CIS, and 10 cancers), for a sensitivity of 25.0±5.2% at specificity of 99.9±0.1%. If DNA assisted cytology were to be used instead, and all cases having 3 or more cells with DNA amount greater than 5c were to be referred to colposcopy and biopsy, then 50 lesions that had to be removed would have been discovered (10 CIN2, 15 CIN3/CIS and 25 cancers) for the sensitivity of 54.3±6.2% at specificity of 96.9±0.6%. Conclusions: The study suggests that screening for high grade cervical neoplastic lesions and cervical cancer by DNA assisted cytology could be implemented with minimal use of skilled cytotechnologists, at least in those countries where it would be difficult to introduce population based screening for cervical cancer due to the lack of availability of such skilled cytotechnologists. Show more

Keywords: Cervical intraepithelial neoplasia (CIN), liquid based sample preparation, image cytometry, DNA ploidy, cytotechnologist shortage, cytology, sensitivity, specificity, invasive cancer

Citation: Analytical Cellular Pathology, vol. 27, no. 1, pp. 33-41, 2005

Authors: Greijer, A.E. | de Jong, M.C. | Scheffer, G.L. | Shvarts, A. | van Diest, P.J. | van der Wall, E.

Article Type: Research Article

Abstract: Hypoxia has clinically been associated with resistance to chemotherapy. The aim of this study was to investigate whether hypoxia induces resistance to doxorubicin and mitoxantrone, two common drugs in cancer treatment, in MCF‐7 breast cancer cells, and SW1573 non‐small lung cancer cells. In addition, the role of drug transporters P‐gp, BCRP and MRP1 was analysed. Hypoxia induced resistance in MCF‐7 cells to mitoxantrone shifted the IC50 value from 0.09 μM (±0.01) to 0.54 μM (±0.06) under hypoxia, whereas survival of MCF‐7 and SW1573 cells in the presence of doxorubicin was not altered. Accumulation of mitoxantrone and daunorubicin, a doxorubicin …fluorescent homologue, appeared to be 5.3 and 3.2 times lower in MCF‐7 cells, respectively. Cytotoxicity assays showed no increased functionality of the drug transporters P‐gp, BCRP and MRP1 under hypoxia. In addition, protein levels of these drug transporters were not changed. Medium of the MCF‐7 cells became more acidic under hypoxia thereby causing a decreased uptake of mitoxantrone. Hypoxia induces mitoxantrone resistance in MCF‐7 cells not mediated by the three major MDR transporters. Hypoxia‐induced acidification may cause this resistance by decreased cellular uptake together with a lowered cytotoxicity due to pH‐dependent topoisomerase type II activity. Show more

Keywords: Acidification, hypoxia, doxorubicin, mitoxantrone, multiple drugs resistance

Citation: Analytical Cellular Pathology, vol. 27, no. 1, pp. 43-49, 2005

Authors: Li, Guorong | Cottier, Michèle | Sabido, Odile | Gentil‐Perret, Anne | Lambert, Claude | Genin, Christian | Tostain, Jacques

Article Type: Research Article

Abstract: Objectives: The common subtypes of renal tumors are conventional or clear cell carcinoma, papillary carcinoma, chromophobe carcinoma and oncocytoma. Each subtype has its distinct histogenesis and clinical evolution. DNA ploidy is viewed as a marker of gross genomic aberrations. The aim of this study is to evaluate the DNA ploidy in the common subtypes of renal tumors to increase our understanding of renal tumor biology and to broaden clinical application of DNA ploidy. Methods: 38 renal tumor samples (13 clear cell RCCs, 12 papillary RCCs, 7 chromophobe RCCs, and 6 oncocytomas) were studied. Five biopsies of different parts of each …fresh tumor were subjected to a flow cytometric analysis of DNA ploidy. Results: All tumors except one papillary RCC generated interpretable DNA histograms. Flow cytometric analysis of oncocytomas showed the diploid pattern (29/30 frequencies) while the chromophobe RCC never showed the diploid pattern (0/55 frequencies) (p<0.01). 3/7 chromopbobe RCCs possessed the hypodiploid stemline. The hypodiploid stemline appeared neither in conventional RCCs (0/63 frequencies) nor in papillary RCCs (0/50 frequencies). The diploid pattern was dominant in conventional and papillary RCCs. 10/13 (76.9%) of clear cell RCCs and 9/11 (81.8%) of papillary RCCs possessed a homogeneous DNA ploidy pattern while only 1/7 (14.3%) has a homogeneous DNA ploidy pattern. 6/7 chromophobe RCCs had multiple aneuploid stemlines. Conclusions: Flow cytometric analysis reveals that conventional and papillary RCCs are more homogeneous than chromophobe RCC. Each subtype of renal tumors possesses a specific DNA ploidy pattern. The analysis of DNA ploidy is useful for the differentiation of common subtypes of renal tumors in morphologically difficult cases. Show more

Keywords: DNA ploidy, renal tumor, differentiation

Citation: Analytical Cellular Pathology, vol. 27, no. 1, pp. 51-56, 2005

Authors: Buffart, T.E. | Coffa, J. | Hermsen, M.A.J.A. | Carvalho, B. | van der Sijp, J.R.M. | Ylstra, B. | Pals, G. | Schouten, J.P. | Meijer, G.A.

Article Type: Research Article

Abstract: Background: C‐Myc, a well‐known oncogene located on 8q24.12–q24.23, is often amplified and over‐expressed in both primary and metastasizing colorectal cancer. In addition, PRL‐3 (also known as PTP4A3), a tyrosine phosphatase located on 8q24.3, is amplified in colorectal cancer metastasis. Beside PRL‐3 and c‐myc, other oncogenes located on the 8q23–24 region might be involved in this process. Therefore, the present study aims to correlate DNA copy number status of a series of genes at 8q23–24 in colorectal cancer at high resolution in correlation to metastatic disease. Materials and methods: Thirty‐two cases of colorectal cancer, 10 stage B1, 10 B2 and 12 …D (Astler–Coller) with their corresponding liver metastasis and one colorectal cell line (colo205, previously analyzed by array‐CGH), were included in this study. A chromosome 8 specific MLPA probe mixture was used to analyze the presence of DNA copy number changes. The probe mixture contained 29 probes covering 25 genes on chromosome 8, as well as 6 control probes on other chromosomes. Results and discussion: MLPA results obtained of the colo205 colorectal cell line were comparable with previous array‐CGH results, thus validating the MLPA probe mixture. Astler–Coller B1 and B2 colorectal cancers differed significantly in DNA copy number of the genes, MOS (p=0.04), MYC (p=0.007), DDEF1 (p=0.004), PTK2 (p=0.02) and PTP4A3 (p=0.04). When comparing these with Astler–Coller D primary tumors, significant differences were seen for several genes as well (MYC (p<0.000), DDEF1 (p<0.000), SLA (p<0.000), PTK2 (p<0.000), PTP4A3 (p=0.002), and RECQL4 (p=0.01)). When comparing primary Astler–Coller D tumors and their corresponding liver metastases, a similar pattern of gains and losses was observed. Most of the liver metastases showed higher DNA copy number ratios than the corresponding primary tumors, but this difference was only significant for TPD52 (p=0.02) and EIF3S6 (p=0.007). Conclusion: In addition to c‐myc, multiple genes on chromosome 8 differed significantly between primary colorectal cancers with and without liver metastases. This observation is consistent with the concept that clinical behaviour, like risk of liver metastasis, is determined by the genomic profile that is already present in the primary tumor. Show more

Keywords: Colorectal cancer, chromosome 8, gene amplification, metastatic disease, MLPA

Citation: Analytical Cellular Pathology, vol. 27, no. 1, pp. 57-65, 2005

Authors: Meijer, Gerrit A.

Article Type: Other

Citation: Analytical Cellular Pathology, vol. 27, no. 1, pp. 67-67, 2005

Article Type: Correction

Citation: Analytical Cellular Pathology, vol. 27, no. 1, pp. 69-69, 2005