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1.
AIMS: To ascertain whether cyclin E immunoexpression relates to clinicopathological characteristics of gastric cancer and is of possible routine use. METHODS AND RESULTS: One hundred and twenty-four gastrectomy specimens were assessed for age, gender, histological subtype, lymph node status and Helicobacter pylori infection. Immunohistochemistry using a commercially available antibody to cyclin E was then applied to the cases. The immunohistochemical staining was correlated with clinicopathological features. Fifty-three of 124 cases were cyclin E-positive, with 28 of these cases showing >50% of the tumour cells staining. However, no statistical significance was obtained between cyclin E immunostaining and any clinicopathological parameter, especially lymph node spread. CONCLUSIONS: We have not demonstrated any significant relationship between cyclin E immunopositivity and any of the usual clinicopathological parameters (especially lymph node involvement) and therefore cyclin E immunohistochemistry alone does not appear to have a role in the assessment of gastric cancer currently.  相似文献   

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BACKGROUND/AIMS: p21(waf) plays a central role both in the regulation of the cell cycle and in DNA replication. Accordingly, p21(waf) is a putative tumour suppressor. The role of p21(waf) expression in breast cancer is still unclear, particularly with respect to the clinical situation. Therefore, this retrospective study was designed to investigate the value of immunohistochemically detected p21(waf) expression in invasive breast cancer. METHODS: Cellular expression of p21(waf) was assessed in 307 breast cancer tissues by immunohistochemistry using the monoclonal antibody, clone 4D10. The data were correlated to established and functional factors of prognosis (age, menopausal status, tumour size, nodal status, tumour grade, receptor status, proliferating cell nuclear antigen (PCNA) expression, Her-2/neu expression, and p53 expression), and to clinical follow up (median observation time, 82 months). RESULTS: Ninety nine of 307 (32.2%) tumour tissues were considered p21(waf) positive (nuclear staining). In the entire study group, p21(waf) expression correlated only with increased PCNA expression (chi(2) test: p = 0.029), and with none of the other investigated markers. In node negative patients (n = 134), p21(waf) expression correlated with increased tumour size and increased PCNA expression, whereas the node positive subgroup (n = 161) showed no correlation with these parameters (lymphonodectomy was done in 295 women). With respect to clinical outcome, p21(waf) expression showed a definite favourable trend in both subgroups (N0: p21(waf) negative, 23 of 87; p21(waf) positive, nine of 43. N+: p21(waf) negative, 63 of 107; p21(waf) positive, 23 of 52), but this observation was not significant (p > 0.05). Multivariate analysis for disease free survival as indicated by Cox regression analysis included all factors investigated. The most striking parameters were nodal status (relative risk (RR), 1.74; p = 0.00001), receptor status (RR, 0.59; p = 0.0085), tumour size (RR, 1.42; p = 0.02), and Her2/neu expression (RR, 1.56; p = 0.033). p21(waf) expression was not significant in the multivariate analysis (p > 0.05). CONCLUSIONS: p21(waf) expression is an independent factor but fails to be of prognostic or predictive value in multivariate analysis. These data confirm the hypothesis of a p53 independent p21(waf) induction and suggest a functional role in the inhibition of PCNA mediated DNA replication.  相似文献   

4.
Estimation of HER2 membranous expression is routinely used in breast and gastric cancers, as both a prognostic and a predictive factor. To date there is no evidence for similar application of HER2 expression in colorectal cancer (CRC) cells. In CRC, HER2 is sometimes overexpressed in the cell membrane and very often in the cytoplasm. This study was conducted to determine possible correlations between both membranous and cytoplasmatic expression of HER2 in CRC cells and the outcome of the disease. The prognostic significance of combined staining intensity in the cell membrane and cytoplasm in the entire CRC cell was also investigated. HER2 expression in resectable colorectal adenocarcinoma cells was evaluated by immunohistochemistry in specimens taken from 202 patients. The percentage of cancer cells with membranous or cytoplasmatic reactions and the staining intensity of the reaction in the whole cell were recorded. A membranous reaction was present in 27% of cases, and cytoplasmatic reaction in 66% of cases. The total staining intensity in the entire cell was evaluated as moderate (2+) in 32% of cases and strong (3+) staining in 15%. There was no correlation found between either membranous or cytoplasmatic HER2 expression and survival. Furthermore combined staining intensity did not provide any prognostic information. We conclude that HER2 expression in CRC does not correlate with prognosis.  相似文献   

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The identification of biomarkers in prostatic carcinoma has yielded important data regarding prognosis and has aided in increasing diagnostic accuracy. Additionally, this approach has yielded important insights into the biology of prostatic carcinoma. In this study, we report that the expression of the cyclooxygenase isoenzyme, COX-2, is significantly increased in prostatic carcinoma, whereas that of the cell adhesion molecule, E-cadherin, is decreased. The expression of COX-2 was positively correlated with higher tumor stage, and the presence of carcinoma in surgical margins at prostatectomy. Conversely, the expression of E-cadherin was inversely related to these prognostic indicators. Lastly, the expressions of COX-2 and E-cadherin were very strongly and inversely correlated. These results provide important insights into the biologic underpinnings of prostate carcinoma; and further studies into COX-2 expression in prostate core biopsies may show utility in preprostatectomy prognostication. Furthermore, these results may provide a rational basis for therapeutic intervention and chemoprevention with COX-2 inhibitor therapy in prostate carcinoma.  相似文献   

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目的:探讨血浆D–二聚体水平与乳腺癌腋窝淋巴结转移的关系,为预测乳腺癌腋窝淋巴结转移状态提供依据。方法:选取乳腺癌患者73例(乳腺癌组),乳腺良性疾病患者36例(良性疾病组)及健康体检女性50例(正常对照组),均检测D–二聚体水平,并结合患者临床及病理资料(肿瘤大小、病理分型、是否淋巴结转移、淋巴结转移个数、激素受体、癌基因等)进行综合分析。结果:乳腺癌组血浆D–二聚体水平明显高于其他两组,差异有统计学意义(P<0.01);乳腺良性疾病组与正常对照组D–二聚体水平比较,差异无统计学意义(P>0.05);腋窝淋巴结转移阳性患者D–二聚体水平高于腋窝淋巴结转移阴性患者,差异有统计学意义(P<0.01);肿瘤大小、病理类型、血浆D–二聚体水平与腋窝淋巴结转移个数显著相关(P<0.01);原发肿瘤的病理类型、血浆D–二聚体水平是腋窝淋巴结转移的危险因素(OR =7.464、6.470);血浆D–二聚体水平诊断乳腺癌腋窝淋巴结转移时的ROC曲线下面积(area under concentration-time,AUC)为0.689,以0.455μg/mL为最佳诊断分界点,灵敏度为52.3%,特异度为86.2%。结论:血浆D–二聚体水平与乳腺癌腋窝淋巴结转移状态及转移个数有关,其对判断乳腺癌腋窝淋巴结转移状态有一定临床价值。  相似文献   

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Interleukin-6 (IL-6) is a pleiotropic cytokine that has been shown to regulate immune defense mechanisms and hematopoiesis. In addition, IL-6 may also be involved in malignant transformation and tumor progression. A poor prognosis in patients with multiple myeloma, renal cell carcinoma, ovarian cancer, or prostate cancer has been associated consistently with elevated IL-6 serum levels. The aim of this study was, therefore, to assess IL-6 serum levels in 68 advanced gastrointestinal cancer patients and to correlate them with prognosis. IL-6 serum levels were found to be significantly elevated in cancer patients with respect to controls. Moreover, patients with disseminated cancer displayed significantly higher IL-6 serum levels than patients without apparent metastases. On univariate analysis, both overall survival (OS) and time to disease progression (TTP) were shown to be affected by IL-6 serum levels. However, multivariate analysis failed to demonstrate an independent prognostic significance for IL-6 serum levels while confirming the role of previously established variables, such as performance status, carcinoembryonic antigen (CEA) serum levels, and distant metastases. In conclusion, this study showed that IL-6 serum levels were elevated in advanced gastrointestinal cancer patients and correlated with both OS and TTP. However, they were shown not to be an independent prognostic factor.  相似文献   

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《Acta histochemica》2014,116(8):1390-1398
We detected MRP1 (multidrug resistance-associated protein 1) and GSTp1 (glutathione-S-transferase p1) protein expression in samples of non-small cell lung cancer (NSCLC) and our results were compared to basic clinicopathological parameters. The indirect immunohistochemical method was used for localization of monitored proteins. A total of 135 tissue samples of NSCLC were characterized according to histopathological type of tumor. Next, we compared our results with basic clinicopathological parameters (histopathological type of tumor, tumor grade and TNM stage of disease). In MRP1 and GSTp1 positive tumor cells, strong brown cytoplasmic immunostaining was visible. In our set of samples 71% showed MRP1 positivity, while according to histopathological type the squamous cell carcinoma reached the highest level of positivity (76%). Our GSTp1 results showed that similarly to MRP1, 70% of samples were GSTp1 positive. According to histopathological type the adenocarcinoma samples showed the highest GSTp1 expression (77%). For precise statistical evaluation the Kruskal–Wallis, Chi-square and Mann–Whitney tests were used. We did not find any statistically significant correlations between MRP1 and clinicopathological parameters. In the group of GSTp1, by Mann–Whitney test we found a statistically significant correlation between GSTp1 and histological grade (p = 0.025) in adenocarcinoma samples. As this was only one group of statistically significant correlation we wanted to confirm this finding. For this we applied also Chi-square test which revealed no statistically significant dependence (p = 0.077). No statistically significant relation was seen in the coexpression of both proteins (p = 0.753). Despite this, the majority of samples simultaneously expressed MRP1 and GSTp1 proteins. In conclusion, our results show that MRP1 and GSTp1 proteins represent independent prognostic features in NSCLC. Nevertheless, the clinical outcome in individual patients is often difficult to predict. Identification of the factors that characterize the resistant cases would permit immediate treatment of the patients with alternative therapeutic approaches.  相似文献   

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Claudins (CLDNs) constitute the major transmembrane proteins of tight junctions. It may be hypothesized that changes in or loss of expression of tight junctional proteins such as CLDNs can lead to cellular disorientation and detachment, which is commonly seen in neoplasia. Recent studies have suggested that claudin-1 (CLDN1) plays an important role in invasion and metastasis and claudin-4 (CLDN4) has a particular role in mammary glandular cell differentiation and carcinogenesis. In this study, we examined 83 breast cancer cases and demonstrated immunohistochemical expression patterns of CLDN1/CLDN4 in recurrent and non-recurrent groups. We found significant results between the recurrent and non-recurrent group for expression of CLDN1/CLDN4. The recurrent group (26 cases) showed decreased expression patterns of CLDN1 (p<0.001), compared to the non-recurrent group (57 cases). Decreased expression of CLDN1 (p<0.0001) correlated with short disease-free interval. The lymph node metastasis-positive group showed decreased expression patterns of CLDN1 (p=0.001). However, there was no significance between the recurrent group and non-recurrent group in CLDN4 expression. There was no significance between histological factors and CLDN4 expression. The results indicated that CLDN1 expression correlated with the recurrence status and malignant potential of breast cancer.  相似文献   

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Aim: The incidence of breast cancer in developing countries still increasing, to identify novel molecular markers associated with carcinogenesis and prognosis of breast cancer still being implemented. The largest subunit of Remodeling and spacing factor (RSF), Rsf-1, mediates ATPase-dependent chromatin remodeling. Its oncogenic properties have been demonstrated in certain carcinomas. The aim of this study was to examine the prognostic value of Rsf-1 in patients with primary breast carcinoma. Methods: A total of 537 patients with primary breast cancer, and 54 with benign breast hyperplasia, were performed resection surgery in the same period were enrolled. Rsf-1 immunoexpression was retrospectively assessed by immunohistochemistry (IHC). As well as, it relationship with clinicopathological factors and patient survival (LRFS, DFS and OS) was investigated. Results: Compared with benign breast hyperplasia tissues, higher percentage of Rsf-1 positive expression was detected in malignant breast carcinomas. Based on IHC staining extent × intensity scores and ROC analysis, 278 of 526 cancers (52.9%) had high-expression (cut-off values 2.5) of Rsf-1, which correlated significantly to pathologic subtypes of breast cancer (DCIS vs. IDC, P < 0.001; ILC vs. IDC, P = 0.036), bigger tumor size (P = 0.030), higher TNM stage (P = 0.044), and p53-positive expression. In addition, there was a trend that high-expression of Rsf-1 associated with younger age (P = 0.053). We further prove that combined positive-expression of Rsf-1 and p53 (Rsf-1 (+)/p53 (+)) was correlated with the bigger tumor size (P = 0.018), and higher TNM stage (P = 0.024). Kaplan-Meier survival analysis showed that Rsf-1 high-expression and combined positive-expression of Rsf-1 and p53 (Rsf-1 (+)/p53 (+)) exhibited a significant correlation with poor overall survival of patients with primary breast cancer, and no association has been identified in relation to LRFS or DFS. Especially, Univariate and multivariate survival analysis demonstrated Rsf-1 expression is an independent prognostic parameter for the overall survival of patients with breast cancer. Conclusions: High-expression of Rsf-1 is associated with pathologic subtypes of breast cancer, aggressive phenotype, p53 positive and poor clinical outcome, which confers tumor aggressiveness through chromatin remodeling, and targeting Rsf-1 gene and the pathway it related may provide new therapeutic avenues for treating breast cancer.  相似文献   

12.
Breast cancer is an increasingly important cause of illness and death among women. In recent years, several novel prognostic determinants of breast cancer have been identified, including Cathepsin-D (CD) protein. CD protein expression was analyzed immunohistochemically (IHC) in tumor specimens (315 patients) of infiltrating ductal breast carcinoma. These patients also had axillary lymph node sampling. Overexpression of CD was observed in 39% of the tumors. IHC results were compared with the histological grade. Seventy nine percent (n = 95; 79%) tumor positivity was seen in grade II tumors, followed by grade I (n = 13; 11%) and grade III tumors (n = 12; 10%). Axillary lymph node metastasis had no significant correlation with CD positivity (p > 0.05). Bone metastases were significantly correlated with CD positivity (p < 0.05). CD positivity showed no significant correlation with disease-free and overall survival (p > 0.05). At a median follow-up of 48 (4 years) months in CD-positive patients, overall survival was 3.17 years, and disease-free survival 2.67 years. The overall survival of CD-negative tumor patients was 3.50 years, and disease-free survival was 2.93 years. We conclude that in comparison with cytosol-based quantitative studies, CD expression is not a good prognostic marker when, as in all ICH studies, only the expression in the tumor is considered.  相似文献   

13.
Bcl-2 and Bax have been demonstrated to be associated with apoptosis in breast carcinoma, and the ratio between Bax and Bcl-2 seems to be an important determinant of cellular sensitivity to induction of apoptosis. However, little information is available on the relationship between Bcl-2, Bax and the proliferative activity of breast carcinoma. The purpose of this study was to investigate the significance of apoptosis-related genes bcl-2 and Bax and their correlation with expression of p53, tumor proliferation defined by MIB-1 expression and estrogen receptor status. Immunohistochemistry was performed to determine Bcl-2, Bax, p53, estrogen receptor (ER) and MIB-1 expression in paraffin-embedded tissues of 177 invasive breast cancers. Expression of the anti-apoptotic protein Bcl-2 was not correlated with the pro-apoptotic Bax. Bcl-2 immunostaining displayed a negative correlation with increasing histologic grade, p53 and MIB-1 (P < 0.0001, P < 0.05 and P < 0.0001, respectively) and a positive correlation with rising ER immunostaining (r = 0.305, P < 0.0001). Conversely, expression of the apoptosis-promoting protein Bax did not correlate with increasing histologic grade, p53, MIB-1 or ER status. Neither Bcl-2 expression nor Bax expression correlated with age, menopausal status, tumor size, histologic type or axillary lymph node status. These results imply that Bcl-2 is associated with good prognostic markers and the regulation of Bax is complex and does not necessarily correlate with mutant p53 status in breast cancers.  相似文献   

14.
The epidermal growth factor receptor (EGFR) is a therapeutic target in a number of settings in solid malignancies, but its role in breast cancer has remained unclear and controversial. In 810 primary breast cancers derived from patients suitable for cytotoxic chemotherapy, EGFR was prospectively measured and interactions with tumour and clinical correlates were tested to observe whether postulated cross-talk mechanisms are likely to modulate breast cancer metastasis and proliferation. A minority (79 tumours, 9.8%) were EGFR positive; in a multivariate analysis the likelihood of being EGFR positive was significantly increased for patients with grade 3 disease, compared with grade 1 (OR 15.6; 95% CI 2 to 122, p=0.0001), and for oestrogen receptor-negative status compared with positive (OR 24.1; 95% CI 12.7 to 46.00, p=0.0001). EGFR expression may play a role in breast cancer proliferation, but appears unlikely to modify tumour pathology via postulated mechanisms of oestrogen receptor/EGFR-mediated cross-talk.  相似文献   

15.
Quantitative measurement of [3H]thymidine [( 3H]TdR) incorporation into cultured cells is widely used as an indicator of cell proliferation. The observation that adult type II cells are able to incorporate large amounts of [3H]TdR despite the fact that they are not proliferating raised the question of the meaning of [3H]TdR incorporation in these cells. Comparing different systems of proliferating and nonproliferating type II cells and lung fibroblasts, we show that nonproliferating type II cells are able to synthesize some thymidine nucleotides used as immediate precursors for DNA synthesis and that most of the radioactivity incorporated into acid-insoluble material in these cells is actually in DNA. We found that hydroxyurea inhibited [3H]TdR incorporation into DNA, suggesting that nonreplicating type II cells use thymidine for scheduled, i.e., replicative, rather than unscheduled, or repair, DNA synthesis. However, newly synthesized DNA does not appear to be in a stable form, available for replication. These studies demonstrate that, in culture, adult type II cells initiate but are unable to complete scheduled DNA synthesis. They also establish that [3H]TdR incorporation cannot be used as an indicator of cell proliferation in cultured type II cells.  相似文献   

16.
Burkholderia pseudomallei is the causative agent of melioidosis but currently the pathogenesis of the disease is still poorly understood. One of the virulent factors of gram-negative bacteria is the ability to produce biofilm to evade host defense. As B. pseudomallei has also been reported to develop the biofilm [1], in the present study, we therefore, quantified the biofilm formation in 50 strains of B. pseudomallei and compared with 50 strains of its avirulent counterpart Burkholderia thailandensis using a modified microtiter-plate test. The results showed that the quantity of biofilm produced by B. pseudomallei was statistically higher (P< 0.01) than that of B. thailandensis (means and SEs of the corrected OD630 were 2.17+/-0.29 and 0.59+/-0.05, respectively). Transmission electron micrographs of the B. pseudomallei strain with high biofilm formation exhibited microcolonies of bacterial cells surrounded by dense extracellular slime matrix comparing with only trace quantity in the low biofilm-producing strain or the biofilm mutants generated by Tn5-OT182 mutagenesis. However, no correlation could be observed between the biofilm formation and virulence, judging from the LD50 values in BALB/c mice. The data obtained with these naturally occurring Burkholderia species and the biofilm mutants are incompatible with the possibility that the biofilm plays a role in the pathogenesis of B. pseudomallei infection.  相似文献   

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The incidence of Candida bloodstream infections (BSIs) has increased over time, especially in medical wards. The objective of this study was to evaluate the impact of different antifungal treatment strategies on 30-day mortality in patients with Candida BSI not admitted to intensive care units (ICUs) at disease onset. This prospective, monocentric, cohort study was conducted at an 1100-bed university hospital in Rome, Italy, where an infectious disease consultation team was implemented. All cases of Candida BSIs observed in adult patients from November 2012 to April 2014 were included. Patients were grouped according to the initial antifungal strategy: fluconazole, echinocandin, or liposomal amphotericin B. Cox regression analysis was used to identify risk factors significantly associated with 15-day and 30-day mortality. During the study period, 130 patients with candidemia were observed (58 % with C. albicans, 7 % with C. glabrata, and 23 % with C. parapsilosis). The first antifungal drug was fluconazole for 40 % of patients, echinocandin for 57.0 %, and liposomal amphotericin B for 4 %. During follow-up, 33 % of patients died. The cumulative mortality 30 days after the candidemia episode was 30.8 % and was similar among groups. In the Cox regression analysis, clinical presentation was the only independent factor associated with 15-day mortality, and Acute Physiology and Chronic Health Evaluation (APACHE) II score and clinical presentation were the independent factors associated with 30-day mortality. No differences in 15-day and 30-day mortality were observed between patients with and without C. albicans candidemia. In patients with candidemia admitted to medical or surgical wards, clinical severity but not the initial antifungal strategy were significantly correlated with mortality.  相似文献   

19.
Background and objectiveBreast cancers are the most common type of cancer and the most common cause of mortality in women worldwide. Different prognostic factors are the subject of research to differentiate the prognosis even between cases at a similar stage and identify risky patients earlier and create individual treatment approaches.Tumor budding (TB) has been identified as a poor prognostic factor in many types of cancer, especially colorectal carcinomas. In our study, we aimed to determine the prognostic significance of the TB by evaluating the TB in line with clinicopathological parameters in breast invasive ductal carcinoma cases.Materials and methods311 breast carcinoma cases operated in our hospital between January 2010 and April 2020 were included in the study. In hematoxylin-eosin (H&E) sections of the cases, TB was evaluated in a single high-power field (HPF). ROC analysis was performed with overall survival data, and low, and high TB cutoffs were obtained. The relationship of the high TB with clinicopathological parameters was evaluated, and survival analysis was performed.ResultsWe determined that high TB in breast invasive ductal carcinoma cases was associated with low survival time, metastasis, axillary lymph node metastasis, angiolymphatic invasion, advanced stage (pT3), high Ki-67 proliferation index, progesterone receptor (PR) loss, and advanced age. Tumor budding was identified as an independent risk factor in overall and disease-free survival analysis.ConclusionTumor budding is a prognostic parameter that can be easily evaluated in all centers since it does not cause additional cost to routine pathological examinations. We think it may be helpful to establish a standard methodology in evaluating tumor bud in breast carcinomas and including it in regular pathology reporting.  相似文献   

20.
C J Howard  P Sopp    K R Parsons 《Immunology》1992,77(2):228-234
L-selectin (LECAM-1, LAM-1) was expressed by a high proportion of CD4+ and CD8+ T cells, as well as almost all of the gamma delta T-cell receptor (TcR)+ (WC1+) T cells, isolated from blood, lymph nodes or tonsils. CD4+ T cells in the lamina propria of the gut villi and CD8+ T cells in the villous epithelium as well as the majority of WC1+ T cells in the gut mucosa were L-selectin-. The proportion of T cells from Peyer's patches that synthesized the molecule was intermediate between the value for blood and gut mucosa. Expression of L-selectin therefore marks T cells in cattle with a distinct tissue distribution that correlates with its function as the peripheral node homing receptor. The proportion of CD4+ and CD8+ T cells in the circulation that were L-selectin+ decreased with age. Unlike CD45R, expression of L-selectin was not related to CD4 T-cell memory as judged by proliferation in transformation assays to soluble antigen. Three-colour immunofluorescent staining demonstrated four subpopulations of CD4 and CD8 T lymphocytes in peripheral blood mononuclear cells (PBMC) that were CD45R+, L-selectin+; CD45R+, L-selectin-; CD45R-, L-selectin+; CD45R-, L-selectin-. CD4(4) memory cells were CD45R- and L-selectin+ or L-selectin-. Taken with earlier studies the reported observations demonstrated that only one of the four phenotypes of the CD4+ T cells in blood is present in the lamina propria of the gut villi and these are CD45R-, L-selectin-. Two of the four phenotypes of CD8+ T cells were present in the gut epithelium; these were CD45R+, L-selectin- or CD45R-, L-selectin-. Expression of the bovine molecule was not rapidly down-regulated on T cells following activation by exposure to phorbol myristate acetate.  相似文献   

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