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S-phase Fraction (s-phase + fraction)
Selected AbstractsOptimizing flow cytometric DNA ploidy and S-phase fraction as independent prognostic markers for node-negative breast cancer specimensCYTOMETRY, Issue 3 2001C.B. Bagwell Abstract Developing a reliable and quantitative assessment of the potential virulence of a malignancy has been a long-standing goal in clinical cytometry. DNA histogram analysis provides valuable information on the cycling activity of a tumor population through S-phase estimates; it also identifies nondiploid populations, a possible indicator of genetic instability and subsequent predisposition to metastasis. Because of conflicting studies in the literature, the clinical relevance of both of these potential prognostic markers has been questioned for the management of breast cancer patients. The purposes of this study are to present a set of 10 adjustments derived from a single large study that optimizes the prognostic strength of both DNA ploidy and S-phase and to test the validity of this approach on two other large multicenter studies. Ten adjustments to both DNA ploidy and S-phase were developed from a single node-negative breast cancer database from Baylor College (n = 961 cases). Seven of the adjustments were used to reclassify histograms into low-risk and high-risk ploidy patterns based on aneuploid fraction and DNA index optimum thresholds resulting in prognostic P values changing from little (P < 0.02) or no significance to P < 0.000005. Other databases from Sweden (n = 210 cases) and France (n = 220 cases) demonstrated similar improvement of DNA ploidy prognostic significance, P < 0.02 to P < 0.0009 and P < 0.12 to P < 0.002, respectively. Three other adjustments were applied to diploid and aneuploid S-phases. These adjustments eliminated a spurious correlation between DNA ploidy and S-phase and enabled them to combine independently into a powerful prognostic model capable of stratifying patients into low, intermediate, and high-risk groups (P < 0.000005). When the Baylor prognostic model was applied to the Sweden and French databases, similar significant patient stratifications were observed (P < 0.0003 and P < 0.00001, respectively). The successful transference of the Baylor prognostic model to other studies suggests that the proposed adjustments may play an important role in standardizing this test and provide valuable prognostic information to those involved in the management of breast cancer patients. Cytometry (Comm. Clin. Cytometry) 46:121,135, 2001. © 2001 Wiley-Liss, Inc. [source] Role of immunocytochemistry and DNA flow cytometry in the fine-needle aspiration diagnosis of malignant small round-cell tumorsDIAGNOSTIC CYTOPATHOLOGY, Issue 4 2001Urmil Brahmi M.Sc. Abstract In the present study, DNA flow cytometry (FCM) and immunocytochemistry (ICC) with a selected panel of antibodies were performed on 51 cases of malignant tumors which were referred for fine-needle aspiration biopsy (FNAB) to our Department of Cytology for the last 2 yr. Twelve cases were diagnosed as neuroblastoma, 16 as Ewing's sarcoma, 2 as retinoblastoma, 5 as non-Hodgkin's lymphoma (NHL), 5 as rhabdomyosarcoma, 2 as peripheral neuroectodermal tumors (PNETs), and 8 as Wilms' tumor. Eleven of 12 neuroblastomas were diploid by FCM, and 1 was aneuploid, with an S-phase fraction (SPF) of 8.3%. Neuron-specific enolase (NSE) was negative in 3 and positive in 8 cases of neuroblastoma, whereas neuroblastoma marker was positive in 3/11. Sixteen of 17 Ewing's sarcomas were diploid, and 1 showed tetraploid aneuploidy, with an SPF of 10.06%. Eight of 13 Ewing's sarcomas were positive for Mic-2 gene product (Ewing's marker). All 5 NHL were positive for leukocyte-common antigen (LCA). Three of 5 rhabdomyosarcomas were diploid, and 2 cases showed aneuploidy. Rhabdomyosarcoma showed muscle-specific actin positivity in 4 and desmin positivity in 3 cases. All 3 cases of PNET were diploid and positive for the Mic-2 gene product, whereas NSE and vimentin were positive in 2 cases. Both cases of retinoblastoma were diploid. Immunostaining was noncontributory in 1 case, and the other showed positivity for the retinoblastoma gene product, NSE, and chromogranin. Seven of 8 Wilms' tumors were diploid, and 1 showed aneuploid, with an SPF of 11.13%. Seven of 8 Wilms' tumors were positive for cytokeratin (CK), 5 were positive for NSE, 6 were positive for epithelial membrane antigen (EMA), and 5 were positive for vimentin. FNAB diagnosis of malignant round-cell tumors is difficult only by light microscopy. Due to the availability of specific markers for subgrouping tumors, ICC has proved to be more useful these days, while DNA FCM has little diagnostic value, as most of them are diploid. Further ancillary studies, e.g., electron microscopy, image analysis, and other molecular investigations, are required to further categorize these tumors more precisely for better clinical management of these cases. Diagn. Cytopathol. 24:233,239, 2001. © 2001 Wiley-Liss, Inc. [source] Lipomatous hemangiopericytoma of the head and neck: immunohistochemical and dna ploidy analysesHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 6 2004Sadir J. Alrawi MD Abstract Background. Lipomatous hemangiopericytoma (LHPC) is a newly described rare soft tissue tumor with unpredictable biologic behavior and is difficult to diagnose by conventional histologic parameters. The molecular analyses of this entity to date are sparse. Only a few cases of LHPC have been reported. Although one case of LHPC in the sinonasal region was briefly reported, this is the first case in the head and neck region with detailed clinicopathologic features and molecular analysis of this entity. Methods. We reported a case of LHPC in a 55-year-old woman with a slowly growing lesion in the occipital area that was diagnosed by CT and MRI and removed surgically. Immunohistochemical and DNA ploidy analyses were performed. Results. A panel of 16 markers was included for immunohistochemical analysis. Diffuse immunopositivity of CD57 in our case provides supportive evidence that LHPC is linked with HPC because this marker is also present in approximately 50% of conventional HPCs. CD57 should be used in the immunohistochemical panel in any lesion suspected to be LHPC. Furthermore, CD57 along with CD34 and XIIIa is thought to stain for primitive mesenchymal stem cells, suggesting a bimodal/multimodal differentiation of LHPC. By flow cytometry, we found that tumor cells were 100% diploid with the S-phase fraction (SPF) being 3.21%. A significant positive correlation was detected between nuclear proliferating index and SPF (p < 0.001, by Spearman analysis). These findings provide molecular evidence indicating a benign nature of LHPC. Conclusions. Contrary to the old belief that HPC has an aggressive nature, this variant of tumor looks less aggressive. The patient was followed for 1 year without any evidence of recurrence, supporting our pathologic hypothesis. © 2004 Wiley Periodicals, Inc. Head Neck26: 544,549, 2004 [source] Can flow cytometrically determined DNA ploidy and S-phase fraction predict regional metastasis in squamous cell carcinoma of the oral cavity?HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 2 2002Ryoichi Oya DDS Abstract Background The value of flow cytometric analysis of DNA ploidy and S-phase fraction (SPF) as an indicator of regional metastasis in oral cancer is currently being debated. Intratumoral heterogeneity makes this problem complex. Methods Intratumoral DNA ploidy heterogeneity and intratumoral SPF variation were examined using multiple specimens from 31 surgically resected specimens taken from patients with oral cancer without preoperative therapy. Flow cytometric analysis of single biopsy specimens from 79 patients with oral cancer was also undertaken to ascertain their value as indicators of regional metastasis. Results Forty-five percent (14 of 31) of tumors showed intratumoral ploidy heterogeneity. Intratumoral SPF variation in the 31 tumors ranged from 0.2% to 6.9% (mean, 3.3%). Multivariate analysis showed that a SPF greater than 27% was the most important parameter for predicting regional metastasis. Conclusions DNA ploidy is heterogeneous within a tumor, whereas SPF is relatively stable and can be correlated with regional metastasis in oral cancer. © 2002 John Wiley & Sons, Inc. [source] Flow cytometry in breast cancer: cell yield using two different fine needle aspiration devicesINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 9 2005R. Freitas Júnior Summary The aim of the study was to compare the quality of breast aspirates obtained by two methods of fine needle aspiration cytology (FNAC): the auto-vacuum device and the syringe pistol holder, using flow cytometry. Both techniques were used in 44 fresh surgical specimens. Subsequently, these specimens were fixed and mounted in paraffin. Both the aspirates and the de-waxed histology material were prepared for flow cytometry using a FACScan. Flow cytometry showed that the means for DNA index and S-phase fraction were similar for aspirates obtained with both techniques. Mean aneuploidy was significantly higher in the auto-vacuum device aspirates than in the surgical specimen (43.4 SD ± 23 vs. 27.9 SD ± 17; p = 0.04). Mean DNA index and S-phase fraction were similar in cells from aspirates and surgical specimens. It is concluded that both FNAC methods are of similar efficacy in collecting aspirates for flow cytometry. [source] Prognostic factors in endometrial carcinomaJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 5 2008Peter Uhar Abstract Endometrial carcinoma is the most common malignancy of the female genital tract in industrialized countries, and occurs predominantly after the menopause. Although most endometrial carcinomas are detected at low stage, there is still a significant mortality from the disease. In postmenopausal women, prolonged life expectancy, changes in reproductive behavior and prevalence of overweight and obesity, as well as hormone replacement therapy use, may partially account for the observed increases of incidence rates in some countries. In order to improve treatment and follow-up of endometrial carcinoma patients, the importance of various prognostic factors has been extensively studied. The identification of high-risk groups would make it possible to avoid unnecessary adjuvant treatment among patients with a good prognosis. Over the past few decades, several studies have demonstrated the prognostic importance of different parameters including lymph node status, histological type of carcinoma (serous carcinoma and clear cell carcinomas are poor prognostic types), histological grade, stage of disease, depth of myometrial invasion, lymphovascular space involvement and cervical involvement. Other factors currently being investigated are estrogen and progesterone receptor status, p53 status, flow cytometric analysis for ploidy and S-phase fraction, and oncogenes such as HER-2/neu (c-erbB-2). [source] The effect of the ionic products of Bioglass® dissolution on human osteoblasts growth cycle in vitroJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 4 2007Jun-Ying Sun Abstract In this study, in order to observe the effect of Bioglass® and its ionic products on human esteoblasts growth cycle in vitro, the ionic products of Bioglass have been introduced to a cell culture medium by dissolving Bioglass particles in Dulbecco's modified Eagle's medium (DMEM) at 37 °C for 24 h; this was used as the experimental medium, while DMEM without Bioglass modification was used as the control medium. Human osteoblasts isolated from trabecular bone were treated by the two media and the timing of the osteoblast growth cycle was examined. Cell growth curves were derived after 7 days. Also, human osteoblasts were treated for 1,6 days by the two media, and the G1, S, G2 phase percentages of osteoblasts were recorded by flow cytometry every day, resulting in the cell proliferation activity index: SPF (S-phase fraction) and PI (proliferation index). The difference in cell growth was shown after the second day of culture (p < 0.01), and cell growth in the experimental groups was greater than in control groups. The SPF and PI of the experimental groups were also higher than the control groups in 2 days of culture (p < 0.05 and p < 0.01), which indicates that the growth cycle of the human osteoblasts in experimental medium is about 2 days. In conclusion, Bioglass can promote osteoblast proliferation, reducing the human osteoblast growth cycle to pass through G1 and S phase and then enter G2 phase quickly. Copyright © 2007 John Wiley & Sons, Ltd. [source] Benign myoepithelioma of the breast: Origin and developmentPATHOLOGY INTERNATIONAL, Issue 6 2009Hajime Hikino A case of benign myoepithelioma of the breast in a 55-year-old woman is described. The tumor was a well-circumscribed solid mass, measuring 13 × 12 mm. Histopathology indicated that the tumor was composed of entirely myoepithelial cells, which was confirmed by immunoreactivity to calponin and S-100. There was no ductal differentiation in the tumor, and staining for pan-cytokeratin and epithelial membrane antigen was weak and negative, respectively. Although the biological behavior of the tumor remains to be ascertained, the tumor was considered to be myoepithelioma with benign features due to mild nuclear pleomorphism, sparse mitotic figures, low Ki-67 labeling index and low S-phase fraction. Diagnostic confusion between benign myoepithelioma and other myoepithelial-rich cell tumors is possible. Considering the classification of myoepithelial tumor in the salivary glands, benign myoepithelioma of the breast may possess a different development process from adenomyoepithelioma. [source] Pancreatitis-Associated Protein Is Related Closely to Neoplastic Proliferative Activity in Patients with Colorectal CarcinomaTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 2 2009Guang Cao Abstract Pancreatitis-associated protein (PAP) is a secretory protein that is not only expressed during acute pancreatitis but also in pancreatic adenocarcinoma, gastric carcinoma, hepatocellular carcinoma, and colorectal carcinoma. Expression in carcinoma might be another characteristic of PAP. The aim of our study was to assess, in 27 patients undergoing surgery for colorectal carcinoma, the expression of the PAP mRNA and to evaluate its association with DNA ploidy and proliferative activity (S-phase fraction, SPF) by reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometric analysis (FCM). PAP mRNA was expressed in 29.6% (8 of 27) of the patients with colorectal carcinoma. DNA aneuploid and high SPF were found in 87.5% (7 of 8) of patients with PAP mRNA positive colorectal carcinoma. The serum PAP level was significantly elevated in patients with colorectal carcinoma when compared with the healthy subjects. Twelve of the 27 patients with colorectal carcinoma had high serum PAP concentrations (>25 ng/mL) and the mean SPF was 17.82% ± 8.02%, which was significantly higher compared with the normal colorectal tissue group (7.33% ± 3.18%, P < 0.05). The mean serum PAP concentration of DNA aneuploidy colorectal carcinomas was 46.67 ± 17.58 ng/mL, which was significantly different when compared with the DNA diploidy group (19.18 ± 8.89 ng/mL, P < 0.05). PAP mRNA expression and serum PAP levels are closely related to neoplastic proliferative activity in patients with colorectal carcinoma. No significant differences are observed between PAP mRNA expression and clinicopathologic parameters (P > 0.05). Anat Rec, 2009. © 2008 Wiley-Liss, Inc. [source] S-phase fraction and DNA ploidy in oral leukoplakiaANZ JOURNAL OF SURGERY, Issue 7-8 2010Rahul Khanna Abstract Background:, The risk of malignant conversion in oral leukoplakia is well documented. Histological findings are often unreliable and it is difficult to predict on the basis of clinical and histopathological changes which leukoplakic lesion will turn malignant. Methods:, We used the technique of flow cytometry to evaluate the ploidy status, DNA index and S-phase fraction in leukoplakia, oral cancer and normal oral mucosal biopsies and compared it with histological findings. The study was carried out on 30 patients with oral cancer, 60 with leukoplakia and 30 with normal oral mucosal biopsies. Results:, The aneuploidy rate in oral cancers was 64%, for leukoplakia 20%, while all normal mucosal biopsies were diploid. Aneuploid lesions also had a greater S-phase fraction (SPF). The DNA Index (DI) of aneuploid oral cancers was 1.72 and aneuploid leukoplakias was 1.24. Leukoplakia specimens which showed histological evidence of dysplasia had aneuploidy rate of 38%, DI of 1.19 and SPF of 6.2%. The corresponding values for leukoplakia specimens without dysplasia were 14%, 1.09 and 4.1%, respectively. Conclusion:, The method of flow cytometry can be used to identify the subset of leukoplakia patients who are at a higher risk of malignant conversion. These patients could undergo more rigid surveillance or undergo excision biopsy of their lesions. [source] Multicentre study of detection and false-negative rates in sentinel node biopsy for breast cancerBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 12 2001Dr L. Bergkvist Background: Sentinel node biopsy has recently evolved as a means of staging the axilla in breast cancer with minimal surgical trauma. The aim of this prospective multicentre study was to identify factors that influencd the detection and false-negative rates during the learning phase. Methods: Data on all 498 sentinel node biopsies performed between August 1997 and December 1999 in Sweden were collected. Results: A sentinel node was found in 450 patients (90 per cent). Preoperative scintigraphy visualized 83 per cent of all sentinel nodes. The detection rate was higher with same-day injection of tracer than with injection the day before (96 versus 86 per cent; P < 0·01). Dye injected less than 5 min or more than 30 min before the start of the operation lowered the detection rate (less than 60 per cent versus more than 65 per cent; P = 0·02). The detection rate varied from 61 to 100 per cent between surgeons. The false-negative rate was 11 per cent. The presence of multiple tumour foci and a high S-phase fraction increased the risk of a false-negative sentinel node, whereas the number of operations performed by each surgeon was less important. Conclusion: Training of the individual surgeon influenced the detection rate, as did timing of tracer and dye injection. The false-negative rate seemed to be related to biological factors. © 2001 British Journal of Surgery Society Ltd [source] Epidermal growth factor receptor expression in breast cancer association with biologic phenotype and clinical outcomesCANCER, Issue 5 2010Mothaffar F. Rimawi Abstract BACKGROUND: Epidermal growth factor receptor (EGFR) expression is associated with aggressive phenotypes in preclinical breast cancer models, but in clinical studies, EGFR has been inconsistently linked to poor outcome. We hypothesized that EGFR expression in human breast tumors, when centrally and uniformly assessed, is associated with an aggressive phenotype and resistance to systemic therapy. METHODS: In a database of 47,286 patients with breast cancer, EGFR status was known on 2567 tumors. EGFR levels were measured centrally by ligand binding assay, and tumors with ,10 fmol/mg were prospectively deemed positive. Clinical and biological features of EGFR-positive and EGFR-negative tumors were compared. Clinical outcomes were assessed by systemic therapy status. RESULTS: Of 2567 tumors, 475 (18%) were EGFR positive. EGFR-positive tumors were more common in younger and in black women, were larger, had a higher S-phase fraction, and were more likely to be aneuploid. EGFR-positive tumors were more likely to be HER2-positive (26% vs 16%, P < .0001), but less likely to be estrogen receptor-positive (60% vs 88%, P < .0001) or progesterone receptor-positive (26% vs 65%, P < .0001). In multivariate analyses, EGFR expression independently correlated with worse disease-free survival (hazard ratio [HR] = 1.66; 95% confidence interval [CI], 1.4-2.41, P = .007) and overall survival (HR = 1.98, 95% CI, 1.36-2.88, P = .0004) in treated patients, but not in untreated patients. CONCLUSIONS: EGFR expression is more common in breast tumors in younger and black women. It is associated with lower hormone receptor levels, higher proliferation, genomic instability, and HER2 overexpression. It is correlated with higher risk of relapse in patients receiving adjuvant treatment. Blocking EGFR may improve outcome in selected patients. Cancer 2010. © 2010 American Cancer Society. [source] | |||||||||||||||||||||||||