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1.
Immunohistochemical staining of osteosarcoma specimens was performed with anti-proliferating cell nuclear antigen (PCNA) monoclonal antibody (PC10, Novocastra) and anti-p53 antibody (DO7, DAKO), using the streptavidinbiotin (SAB) method. The average PCNA labeling index was 55.3% and all patients with a labeling index higher than 68% died of diesease. p53 expression was 40.9% and the labeling index was 33.3% in patients who were continuously disease-free, but the index was 37.9% (average) in patients who died of disease; all patients with an index higher than 50% died of disese. However, in patients with metastasis, the p53 index was low in patients who survived after resection of the metastasis, suggesting that this profile may reflect the metastatic behavior of the tumor. We often perform preoperative chemotherapy for osteosarcoma and we consider that markers of the effect of chemotherapy are important in predicting survival. It seems that an increase in the PCNA labeling index and an increase in the p53 labeling index or in p53 expression after chemotherapy indicates a good prognosis.  相似文献   

2.
大肠癌组织及其癌旁粘膜PCNA和AgNORs的检测及其临床意义   总被引:2,自引:0,他引:2  
目的 探讨大肠癌组织及癌旁粘膜中增殖细胞核抗原 (PCNA)的表达和核仁区嗜银染色 (AgNORs)计数的临床意义。方法 采用免疫组织化学 (SP法 )和嗜银染色技术对 48例大肠癌组织及其癌旁粘膜和 1 0例正常大肠粘膜中PCNA和AgNORs进行检测。结果 大肠癌组织中PCNA标记指数 (PCNA LI)和AgNORs计数均显著高于癌旁 3cm和 6cm粘膜及正常粘膜 (P<0 .0 1 ) ,PCNA LI在DukesC期和D期显著高于DukesA期 (P<0 .0 5)。癌旁 3cm粘膜细胞AgNORs计数显著高于癌旁 6cm粘膜 (P<0 .0 1 )及正常粘膜细胞的AgNORs计数 (P<0 .0 5)。结论 大肠癌癌旁粘膜部分细胞增殖调节失控 ,提示癌旁粘膜是一种不稳定的癌前状态 ,可能与大肠癌术后复发有关  相似文献   

3.
BACKGROUND: The MACIS score uses metastasis, age, completeness of resection, local invasion, and tumor size to stratify patients with papillary thyroid carcinoma (PTC) into four groups with different survival. METHODS: Immunostaining for proliferating cell nuclear antigen (PCNA) was done in 43 cases of PTC. Relationships between proliferative index (percentage of cells that were PCNA positive) and the MACIS parameters were examined. Double staining for PCNA and for silver-stained nucleolar organizer regions (AgNORs, indicating proliferation) was performed in 10 cases. RESULTS: PCNA was detected only in tumor cells. The proliferative index was low (mean, 14.2%; median, 13.0%), did not differ between MACIS groups (p = 0.56), and showed no association with individual MACIS parameters. PCNA immunostaining correlated with AgNOR staining. The mean AgNOR count was 2.28 in PCNA-positive cells and 1.85 in PCNA-negative cells (p 相似文献   

4.
Nucleolar organizer regions in bone tumors   总被引:3,自引:0,他引:3  
Silver-stained nucleolar proteins (AgNORs) were counted in a variety of bone tumors. In osteosarcomas, the number of AgNORs was also quantified before and after chemotherapy. Malignant bone tumor cells possessed more than five small AgNORs (5.85 +/- 1.39). Nuclei of benign bone tumor cells had less than three (2.61 +/- 0.51). A significant difference in the number of AgNORs between osteosarcomas before chemotherapy (6.10 +/- 1.22) and after chemotherapy (4.20 +/- 1.07) was observed. (p less than 0.001). The number of AgNORs in osteosarcoma patients with better prognoses was smaller than that of osteosarcoma patients showing poor prognoses, but without significant difference. The results of the present study indicate that the AgNOR count might help in determining malignancy, evaluating the effect of chemotherapy, and deciding the prognosis.  相似文献   

5.
目的:研究大鼠失神经支配皮肤切割伤愈合过程中修复细胞增生活性的变化。方法:40只SD大鼠随机分成T、C两组(每组20只),在其背部形成全层皮肤切割伤缺损创面,其中T组为手术损伤鼠T11~L12脊神经皮肤切割伤组,C组为正常有神经支配的皮肤切割伤组,在伤后1、2、3、4周,观察创面愈合,A、B两组同时取材,采用免疫组化和银染法,检测创面修复细胞PCNA的表达和AgNORs颗粒数的变化。结果:T组较C组创面愈合明显延迟,同时修复细胞PCNA表达明显减弱,细胞核内AgNORs颗粒数明显减少,第3周两组的创面PCNA标记指数和AgNORs计数分别为2.11%/18.1%(P=0.001),1.1/3.1个/细胞(P<0.05)。结论:大鼠失神经支配皮肤切割伤愈合较正常创面愈合明显延迟,修复细胞增殖活性明显降低。  相似文献   

6.
Nucleolar organizer regions in meningioma   总被引:1,自引:0,他引:1  
Seventy-eight cases of meningioma and related tumors were examined independently using a simple and reproducible argyrophilic method for the demonstration of nucleolar organizer regions (AgNORs) and staining with bromodeoxyuridine monoclonal antibody. The mean number of AgNORs per cell and the bromodeoxyuridine labeling index were shown to be linearly related (r = 0.84, P less than 0.001). The mean AgNOR number was 2.99 for meningeal sarcoma, 2.29 for anaplastic meningioma, 2.08 for hemangiopericytic meningioma. 1.72 for recurrent meningioma without atypical histological findings, and 1.52 for nonrecurrent meningioma. We noted that the mean number of AgNORs reflected the cellular kinetics of a tumor and was related to histological grade and clinical behavior.  相似文献   

7.
By flow cytometry, cellular DNA-RNA content was analyzed with Acridine Orange staining for primary tumor and the metastatic foci in 12 cases of primary lung carcinoma. Five (42%) of the primary and metastatic foci showed heterogeneous cellular DNA content, with high cellular DNA content of metastatic foci in all cases. Cellular RNA content was significantly higher in metastatic foci than in primary foci, indicating possible higher proliferative activity of the former foci. Three different metastatic foci in one patient showed essentially the same cellular DNA content. From the above it is evident that primary and metastatic foci of lung carcinoma show considerable heterogeneity not only in cellular DNA content but RNA content as well, thus indicating proliferative activity of the metastatic focus. It is consequently advisable to use a combination of various supplementary medications differing in cytocidal effect. Cases with higher cellular DNA content may likely have higher metastatic potential.  相似文献   

8.
Tumor differentiation and proliferative activity are important predictors of biological behavior. While routine histological evaluation is fairly adequate to assess differentiation, tumor proliferative activity is difficult to measure. Silver staining for nucleolar organizer regions (AgNORs) is reported to be helpful for assessing tumor proliferation. We investigated the AgNOR counts in 20 formalin fixed, paraffin embedded human prostate tissues in three microscopic fields of 330X, using an image analysis system. A total of 200–700 nuclei were evaluated on histologically controlled areas of nonneoplastic prostate tissue, prostatic intraepithelial neoplasia (PIN), and invasive carcinoma. The values were compared to flow cytometrically obtained synthesis phase fractions (SPF) and immunohis-tochemically semi-quantitated, proliferative cell nuclear antigen (PCNA) patterns. AgNOR counts were also compared to tumor stage and Gleason's score. The pattern of PCNA staining in formalin fixed specimens was widely variable, probably due to differences in preservation of antigen. The positive counts varied from 0 to 55%, with a mean value of 8.55 ± 15.9. The SPF values ranged from 5 to 13% with a mean value of 8.50 ± 2.37. Two of 20 tumors were aneuploid and 18 were of diploid range. The mean AgNOR values in nonneoplastic nuclei (1.836 ± 0.299), PIN (3.129 ± 0.295), and invasive tumor cell nuclei (4.737 ± 0.369) were highly significant (P < 0.0001) when paired differences were compared. AgNOR counts correlated significantly with tumor Gleason's score (P < 0.0145). However, the correlation coefficient for SPF and AgNOR values was not significant (P > 0.24), possibly because of the small number of samples examined. The highest AgNOR counts were found in the two aneuploid tumors. We conclude that AgNOR count may be a potential indicator of cellular proliferation, and possibly a marker of tumor differentiation. © 1993 Wiiey-Liss, Inc.  相似文献   

9.
胃肠道平滑肌肿瘤nm23表达与细胞增殖活性关系的研究   总被引:2,自引:0,他引:2  
Wang Q  Sun W  Zhao Y  Wang M  Qin Y  Fu Y 《中华外科杂志》1998,36(7):427-429
目的探讨nm23表达与胃肠道平滑肌肿瘤(GISMT)良恶性、恶性程度、转移、预后及细胞增殖活性的关系。方法采用免疫组化法检测86例GISMT患者nm23的表达情况,采用胶银染色法及免疫组化法检测核仁组成区嗜银蛋白(AgNORs)、增殖细胞核抗原(PCNA)来反映细胞的增殖活性。结果nm23的表达按平滑肌瘤、低度恶性平滑肌肉瘤、高度恶性平滑肌肉瘤的顺序依次明显下降(P<0.01)。nm23表达与肿瘤的良恶性生长方式、大小、中心有无坏死亦有明显的关系(P<0.01或P<0.05)。nm23阳性表达组的5年生存率明显高于阴性表达组(P<0.05)。nm23阴性组的AgNORs和PCNA表达明显高于nm23阳性表达组(P<0.01)。结论nm23是反映GISMT生物学特性的良好标志物,与AgNORs、PCNA可互补作为判断GISMT良恶性、恶性程度、转移及预后的客观指标。  相似文献   

10.
BACKGROUND: To clarify the significance of basic fibroblast growth factor (bFGF) in angiogenesis or proliferative activity in cardiac myxoma, the expression of bFGF and its receptor (FGFR-1) were immunohistochemically examined. METHODS: Formalin-embedded tissues of cardiac myxomas were obtained by surgical resection from 15 patients and analyzed by immunostaining of bFGF and FGFR-1. The microvessel density was measured in the 15 myxomas using platelet derived endothelial cell adhesion molecule-1. For evaluation of proliferative activity of the cardiac myxomas, proliferating cell nuclear antigen (PCNA) immunostaining was performed, and the PCNA labeling index was measured in each section. RESULTS: bFGF and FGFR-1 were observed in 73.3% and 67.7% of the myxomas, respectively. There was a close correlation between the expression of bFGF and FGFR-1. This co-expression was frequently observed in the myxoma cells around the microvessels appearing as a ring structure. Regarding possible relationships between the expression of bFGF or FGFR-1 and the clinicopathologic features, there were no parameters excluding the macroscopic type of myxoma. The microvessel density in the myxomas with bFGF or FGFR-1 expression was higher than that in myxomas without it. The PCNA labeling index in myxomas with bFGF expression was higher than that in myxomas without it, and the PCNA labeling index tended to be higher in myxomas with FGFR-1 expression than that in myxomas without it. CONCLUSIONS: bFGF and/or FGFR-1 was expressed in some of cardiac myxoma, and may be an important role for tumor angiogenesis and proliferative activity.  相似文献   

11.
The number of nucleolar organizer regions in vascular cells and neoplastic cells of human gliomas was counted by a combined staining technique: one-step silver colloid method for nucleolar organizer region-associated argyrophilic protein (AgNOR) and periodic acid-Schiff staining for basement membrane of vascular components. The number of AgNORs (mean +/- SD) in the vascular and neoplastic cells of various tumors tested was as follows: benign astrocytoma (Grade 2, n = 4), 1.52 +/- 0.07 and 1.80 +/- 0.13, respectively; anaplastic astrocytoma (Grade 3, n = 7), 1.98 +/- 0.23 and 2.87 +/- 0.50; and glioblastoma multiforme (Grade 4, n = 11), 2.05 +/- 0.29 and 3.13 +/- 1.13. AgNOR scores in vascular cells of benign astrocytomas, anaplastic astrocytomas, and glioblastomas were significantly higher than those of vascular cells in normal brain tissue without neoplastic alteration (1.26 +/- 0.05; n = 3; P less than 0.01, P less than 0.001, and P less than 0.001, respectively). Moreover, the AgNOR scores of vascular cells in high-grade gliomas (Grades 3 and 4) were significantly higher than those in low-grade gliomas (Grade 2) (P less than 0.01). These results indicate that the proliferative activity of both vascular and neoplastic cells in gliomas increased as histological malignancy advanced, and that the quantification of AgNORs was useful in evaluating proliferative activity in vascular cells as well as in assessing the malignancy of neoplastic tissues.  相似文献   

12.
This study compares the metabolism of [14C]-arachidonic acid between PGE2 synthesizing (ROS 17/2.8) and nonsynthesizing (ROS 25/1) osteosarcoma cell lines. In both cell lines: (a) 90% of [14C]-arachidonic acid was taken up at 24 h. (b) More than 90% of the label was associated with phospholipids. (c) [14C]-arachidonic acid was rapidly taken up by phosphatidylcholine which reached the highest specific activity around 5 h while the labeling of other phospholipids was still increasing at 24 h. (d) Twenty-four hours after addition of [14C]-arachidonic acid only 4% of the label was associated with triacylglycerols in ROS 25/1 and 0.3% in ROS 17/2.8 cells. The calcium ionophore A23187 enhanced the release of [14C]-arachidonic acid from phospholipids in the PGE synthesizing osteoblastic cells (ROS 17/2.8 and 2/3) but had no effect in nonosteoblastic cells (ROS 24/1 and 25/1). ROS 17/2.8 and 2/3 cells converted the released arachidonic acid as well as exogeneously added arachidonic acid into PGE2. PGE2 synthesis depended on arachidonic acid concentration. Among bone resorbing agents, parathyroid hormone and 1,25(OH)2D3 had no effect on PGE synthesis, whereas thrombin and rabbit serum stimulated PGE2 production. The effect of rabbit serum was abolished by heat inactivation. The findings of this study indicate that the difference in PGE production between the osteoblastic and nonosteoblastic osteosarcoma cells are due mainly to differences in arachidonic acid conversion to PGE2.  相似文献   

13.
The results of surgical resection for pulmonary metastases from colorectal, breast, and renal cell carcinomas, soft tissue sarcoma, and osteosarcoma are reviewed. The number of pulmonary metastases, the presence of hilar or mediastinal involvement, and extrapulmonary foci are discussed in terms of surgical treatment. The size of pulmonary tumors or tumor doubling time has no significant effect on survival, while the number of metastatic foci does. Although a slight survival advantage has been noted for patients without hepatic metastases from colorectal cancer before pulmonary metastases occur, the difference in survival rates among patients with and without hepatic metastases is not significant. The role of surgery is less clear in breast cancer patients, and therefore further prospective study is considered essential. Higher relapse rates have been reported in patients with soft tissue sarcoma and osteosarcoma, although patients with these metastases can achieve long-term survival after a second metastasectomy. VATS is not be recommended for metastatic cancer surgery, because intraoperative identification of metastatic foci is often difficult.  相似文献   

14.
Background This study investigated whether the expression of vascular endothelial growth factor (VEGF) in a primary tumor and the intratumoral microvessel density (MVD) were independent prognostic factors in patients with an esophageal squamous cell carcinoma (SCC) in comparison with positron emission tomography (PET) by using 18F-fluorodeoxyglucose (FDG) and stage. Methods Fifty-one patients with a newly diagnosed esophageal SCC who underwent preoperative FDG-PET and esophagectomy with intent to cure were enrolled in this study. The VEGF expression level, the intratumoral MVD, and the Ki-67 labeling index were evaluated by using immunohistochemical staining. Only significant variables in the univariate survival analysis were examined by multivariate survival analysis with the Cox proportional hazards model. Result Cancer-related deaths occurred in 17 of 51 patients during the follow-up. Univariate survival analysis showed that the pathologic stage, pNM, maximum standardized uptake value of the primary tumor, tumor length on PET, number of PET-positive lymph nodes, PET stage, Ki-67 labeling index, intratumoral MVD, and the presence of VEGF expression were significant prognostic predictors for the overall survival. Multivariate analysis revealed that the pathologic stage, number of PET-positive nodes (0, 1, 2, or ≥3), intratumoral MVD (cutoff, 60/mm2), and presence of VEGF expression were independent significant prognostic predictors for overall survival. Conclusion In addition to the pathologic stage, the intratumoral MVD, the presence of VEGF expression, and the number of FDG-PET–positive nodes were independent prognostic predictors in patients with an esophageal SCC undergoing curative surgery.  相似文献   

15.
The Ki67 labeling index is known to correlate with survival in patients with neuroendocrine tumors (NETs). A grading scheme recently endorsed by the World Health Organization for gastroenteropancreatic NETs classifies well-differentiated NETs into 2 categories based on the Ki67 labeling index: low (G1) and intermediate grades (G2). Tumor heterogeneity is a common finding in many tumors including NETs. Metastatic NETs to the liver are often diagnosed by radiographically guided needle core biopsy from which the Ki67 index is determined, which randomly samples the lesion without being targeted to regions that may show a higher proliferative rate. Whether the Ki67 index obtained from this type of limited material represents the whole tumor has been questioned. Forty-five surgically resected liver metastases of well-differentiated NETs were retrieved. A 9 core (3 core-triplets) tissue microarray (TMA) was constructed from the paraffin blocks of each tumor, each triplet considered to represent a virtual biopsy. Immunohistochemical staining for Ki67 was performed on TMA and whole slides, and the Ki67 labeling indices were determined by digital image analysis. Correlation of the Ki67 index with patient survival was analyzed. Forty-seven percent of cases showed intratumoral heterogeneity in Ki67 index that translated into discrepant grades among subsections on the whole slide. A similar trend was recapitulated on the virtual biopsies, although to a lesser degree. When the definitive grade of the tumor was based on the highest Ki67 index identified on the whole slide, the virtual biopsies perfectly predicted G1 cases (100%), but were much less accurate for G2 cases (47.8% with 3 biopsies and 34.8% with single biopsy). Accordingly, the predictive value for G1 on the virtual biopsies was low (64.7% and 59.5% for 3 and 1 biopsy, respectively), but was perfect for G2 (100%). By Kaplan-Meier survival analysis, there was a statistically significant difference between G1 and G2 in terms of overall survival, disease-free survival, and progression-free survival when graded on either whole-slide subsections or virtual biopsies. On the whole slides, the highest Ki67 grade showed a better correlation with overall survival than the mean Ki67 grade. In summary, by image analysis, we found that about half of the NETs metastatic to the liver show intratumoral heterogeneity resulting in discrepant Ki67 grade. In most cases, in particular G1, the virtual biopsy is representative of the whole slide, but for G2 the representation is <50%. Nevertheless, grades based on virtual biopsy had statistically significant prognostic values on patient survival, and there is no clear difference between the 3 and single virtual biopsy. Ki67 staining of core biopsies usually provides an adequately reliable method of proliferation assessment for prognosis of metastatic NETs to the liver, although the choice of treatment may be affected by intratumoral grade heterogeneity.  相似文献   

16.
A series of 8 rat and 16 mouse invasive bladder carcinomas were investigated for the presence of silverstained nucleolar organizer regions (AgNORs) to clarify whether this parameter is applicable to the estimation of their invasive character. With regard to number of AgNORs per cell, neither rat nor mouse carcinomas showed any difference between invasive and noninvasive sites within the same tumor. However, the frequency of cancer cells bearing bizarre dots, irregular in size and shape, was significantly higher at sites of actual invasion. Quantitative data generated using an image analyzer revealed significantly lower values for NOR roundness and significantly larger NOR size in invasive sites than in noninvasive sites in all groups. Double staining for the proliferation marker proliferating cell nuclear antigen (PCNA) and AgNORs was performed on eight rat carcinomas and a close correlation between the two was confirmed. Thus the number of AgNORs in PCNA-positive cells was significantly greater than in PCNA-negative cells. Furthermore, a particularly strong correlation was observed for incidences of PCNA-positive cells and bizarre dots (P<0.01). The quantitative data also demonstrated significant differences in size and shape of dots. It is concluded that AgNORs have diagnostic value for the invasive character of bladder carcinomas.  相似文献   

17.
Summary The potential of clonal rat osteosarcoma (ROS) cell lines to form mineralized matrices was assessed in diffusion chambersin vivo. Diffusion chambers were inoculated with osteoblastic (ROS 17/2 and its subclone ROS 17/2.8) and nonosteoblastic (ROS 24/1) clonal lines and implanted either intraperitoneally into athymic mice or subcutaneously into syngeneic ACI rats. Control chamber cultures of rabbit marrow or spleen cells were also incubated in athymic mice. Light and electron microscopy of chambers with ROS 17/2 and ROS 17/2.8 cells revealed production of mineralized matrices typical of osteosarcoma and characterized by abundance of collagen fibrils and associated mineralizing nodules. ROS 24/1 cells produced similar collagenous matrices, but these were devoid of mineral. The present experiments, carried out independently in two different laboratories, demonstrate the potential of ROS cells to produce a mineralized matrix. This corroborates previous studies on other osteoblastic features of these cell lines.  相似文献   

18.
目的采集手术切除未经培养的骨肉瘤标本,研究肿瘤中成骨细胞的分化及其与临床因素的关系。方法观察骨肉瘤中成骨细胞相关基因表达的频率、特异性,以及骨肉瘤成骨细胞表型与生物学行为的关系。应用RT-PCR方法研究48例骨肉瘤标本的碱性磷酸酶(ALP)、骨钙素(OC)和骨桥蛋白(ON)的mRNA转录。磷酸甘油酸激酶(PGK)被用于内参照。结果在大多数骨肉瘤标本中可以发现ALP或OC的mRNA转录(分别为93.75%,79.17%)。在所有的肉瘤检测中均可发现ON的mRNA转录。在骨肉瘤的成骨细胞亚型中可见到ALP和OC的高水平表达。肺转移瘤OC的mRNA表达弱于原发灶。肿瘤细胞有高水平OC表达的病例组有较高的生存率(P=0.045)。结论OC是目前最好的成骨细胞特异性标记物,将来可能用于检测骨肉瘤患者外周血中循环的肿瘤细胞。  相似文献   

19.
Distinguishing between grade II and grade III diffuse astrocytomas is important both for prognosis and for treatment decision-making. However, current methods for distinguishing between grades based on proliferative potential are suboptimal, making identification of clear cutoffs difficult. In this study, we compared the results from immunohistochemical staining for phospho-histone H3 (pHH3), a specific marker of cells undergoing mitosis, with standard mitotic counts (number of mitoses/10 high-power fields) and MIB-1 labeling index values for assessing proliferative activity. We tested the relationship between pHH3 staining and tumor grade and prognosis in a retrospective series of grade II and III infiltrating astrocytomas from a single institution. The pHH3 index (per 1000 cells), MIB-1 index (per 1000 cells), and number of mitoses per 10 high-power fields were determined for each of 103 cases of grade II and III diffuse astrocytomas from patients with clinical follow-up. pHH3 staining was found to be a simple and reliable method for identifying mitotic figures, allowing a true mitotic index to be determined. The pHH3 mitotic index was significantly associated both with the standard mitotic count and with the MIB-1 index. Univariate analyses revealed that all 3 measurements of proliferation were significantly associated with survival. However, the pHH3 mitotic index accounted for a larger proportion of variability in survival than standard mitotic count or MIB-1/Ki-67 labeling index. After adjusting for age, extent of resection, and performance score, the pHH3 mitotic index remained an independent predictor of survival. Thus, pHH3 staining provides a simple and reliable method for quantifying proliferative potential and for the stratification of patients with diffuse astrocytomas into typical grade II and III groups. These results also suggest that pHH3 staining may be a useful method in other neoplasms in which accurate determination of proliferation potential is relevant to tumor grading or clinical treatment decision-making.  相似文献   

20.
胰腺癌组织中增殖细胞核抗原的表达及临床意义   总被引:5,自引:0,他引:5  
目的 为了探讨增殖细胞核抗原(PCNA)的表达与胰腺癌组织生物学行为及预后的关系。方法 采用LABC法免疫组化染色检测32例胰腺癌和14例慢性胰腺炎组织中的PCNA表达。结果 PCNA在胰腺癌组织中的表达率为100%,胰腺癌组织中的PI明显高于慢性胰腺炎组织(P<0.01)。PI 值与随肿瘤进展而逐渐增加的趋势,且PCNA表达与胰腺癌的预后呈负相关(P<0.01)。结论PCNA表达能反映胰腺癌组织的增殖活性,分化程度越低,PCNA表达强度越高,它可作为预测胰腺癌病程和预后的一个有用指标。  相似文献   

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