Prognostic value of Ki 67/MIB1 automated and quantitative immunolabelling in primary operable breast carcinomas

The prognostic significance of Ki 67/MIB1 immunohistochemical assays (ICAs) was investigated in optimal technical conditions in 139 breast carcinomas. Automated ICAs (immunoperoxidase/Ventana device) was performed on frozen sections. Immunoprecipitates were quantified by computerized analysis (SAMBA) of digitized microscopic images. Mean positive surfaces (%) and quantitative immunocytochemical (QIC) index were correlated to the patients survival (8-year survival). The results showed that Ki 67/MIB1 large surfaces (cutpoint, 20%) and high QIC index (cutpoint, 12) correlated with poor overall survival (Kaplan Meier, log rank test, p=0.011 and p=0.037, BMDP software). In node positive, but not in node negative patients, large Ki 67/MIB1 surface (cutpoint, 20%) and high QIC index (cut-off 12) correlated with the overall patient survival (p=0.0037 and p=0.049). Also large Ki 67/MIB1 positive surface (cut-off, 20%) correlated with disease-free survival in all patients and node positive patients (p=0.022 and p=0.0057) but not in node negative patients. It is concluded that in optimal technical conditions (automated and quantitative immunohistochemical assays on frozen sections) Ki 67 antigen immunohistochemical expression in breast carcinomas tissue has a prognostic significance in node positive patients but not in node negative patients.     

Tumor neoangiogenesis by CD31 and CD105 expression evaluation in breast carcinoma tissue microarrays.

PURPOSE: The aim of the study was to evaluate CD31 and CD105 immunohistochemical expressions in tissue microarrays from 360 breast carcinomas. STUDY DESIGN: Computerized (ACIS/Chromavision) assisted image analysis was performed to compare immunoreactions in tissue microarrays with those in current paraffin and frozen sections. We also aimed to determine the CD105 and CD31 prognostic significance and relevance in routine practice by correlating results of immunodetections with patients' (n = 360) outcome (14.3-year follow-up). RESULTS: The results show (a) that in tissue microarrays, the CD31 and CD105 expression quantified by image analysis device did not correlate with the measurements assessed on routine paraffin sections; (b) that CD105 expression is endowed of a prognostic significance in paraffin sections in terms of overall survival (P < 0.01), whereas in contrast, CD31 on paraffin sections did not correlate with patients overall survival; (c) that semiquantitative analysis of CD105 expression correlated with the image analysis measurements in frozen sections (rho = 0.671, P < 0.01) and paraffin (rho = 0.824, P < 0.01) sections. However, paraffin sections were less immunostained than frozen ones. CONCLUSIONS: It is concluded (a) that CD105 may be suitable in paraffin sections to evaluated neoangiogenesis; and (b) that tissue microarrays are not suitable substrates for neoangiogenesis evaluation as a prognostic indicator in breast carcinomas, in contrast to current tissue sections.     

Prediction of metastasis risk (11 year follow-up) using VEGF-R1, VEGF-R2, Tie-2/Tek and CD105 expression in breast cancer (n=905)

Neoangiogenesis in tumours contributes to the development of blood-borne metastases, and can be evaluated by markers of activated endothelial cells in preference to panendothelial markers. Our purpose was to document the prognostic significance of VEGF-R1, VEGF-R2, Tie-2/Tek and CD105 immunoexpression in breast carcinoma frozen samples (n=905, follow-up=11.7 years). We observed that: (i). CD105 (P=0.001) and Tie-2/Tek (P=0.025) (but not VEGF-R1 and VEGF-R2) overexpression correlated with a shorter survival, and were (Cox's model) independent histoprognostic indicators; (ii). only CD105 marked expression correlated (P=0.035) with a shorter survival of node-negative patients; (iii). three markers - CD105 (P=0.001), Tie-2/Tek (P=0.01), VEGF-R1 (P=0.001), but not VEGF-R2 - correlated with metastatic risk in node-negative patients in univariate analysis; and (iv). VEGF-R1 (P=0.01) expression correlated with high local recurrence risk. It is concluded that CD105 and to a lesser extent Tie-2/Tek and VEGF-R1, but not VEGF-R2 are endowed with prognostic significance that may be useful for patient monitoring, particularly CD105 expression for selecting node-negative patients for more aggressive postsurgery therapy.     

Comparison of the prognosis indication of VEGFR-1 and VEGFR-2 and Tie2 receptor expression in breast carcinoma

The degree of angiogenesis in breast cancer has previously been shown to be an indicator of prognosis, and tumor microvasculature is a candidate target for new antiangiogenic therapies. The aim of this study was to investigate the prognostic value of vascular endothelial growth factor (VEGF) receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1), and Tie2/tek receptor tyrosine kinase in breast carcinoma. VEGF receptors and Tie2 expression was investigated using immunohistochemical assays with monoclonal antibodies on frozen sections in a series of 918 and 909 patients respectively. VEGFR-1 and VEGFR-2 and Tie2 were correlated with long-term (median, 11.3 years) patients' outcome. Univariate (Kaplan-Meier) analysis showed that VEGFR-1 positive tumor surface (cutoff = 5%) was significantly correlated with high metastasis risk (p=0.03) and relapse (p<0.01) in all patients, and in those with node negative tumors (p<0.001 and p<0.01 respectively), but not with overall survival. In contrast Tie2 positive tumor surface (cutoff = 7%) was significantly correlated with poor overall survival (p=0.025) and also with high metastasis risk particularly among node negative patients (p<0.01). Moreover, Tie2 immunoexpression was significantly predictive of relapse (p=0.003) in the node negative subgroup (p=0.02). In multivariate analysis (Cox model), VEGFR-1 and Tie2 immunoexpressions were identified as independent prognostic indicators. In contrast, univariate analysis showed that VEGFR-2 positive tumor surface (cutoff = 10%) was not correlated with survival or with metastasis and relapse risk. Our results suggest that VEGFR-1 and Tie2 immunohistochemical expression permits the identification of patients with poor outcome, and particularly node negative ones with a high risk for metastasis and relapse. VEGFR-1 and Tie2 immunodetection may also be considered as potential tools for selecting patients who could benefit in the future from specific antiangiogenic therapy interfering with VEGFR-1 and Tie2 activation pathways.     

Prognostic value of tumor-infiltrating dendritic cells expressing CD83 in human breast carcinomas

DCs are the most potent antigen-presenting cells that play a major role in initiating the antitumor immune response. Although the clinical significance of TIDCs has been investigated in a variety of human cancers, few studies have focused on the in situ maturation status of DCs. We have analyzed the maturation-specific significance of TIDCs in the prognosis of patients with breast carcinoma. We evaluated 130 breast carcinomas for the presence of TIDCs using immunohistochemistry with an anti-CD1a antibody for immature DCs and an anti-CD83 antibody for mature DCs. Intratumoral expression of immunosuppressive cytokines was also examined. All samples contained CD1a(+) TIDCs, and 82 (63.1%) samples contained CD83(+) TIDCs. The number of CD83(+) TIDCs was inversely correlated with lymph node metastasis and with tissue expression of VEGF and TGF-beta, whereas the number of CD1a(+) TIDCs was not. Kaplan-Meier analysis (log rank statistics) revealed a significant association of increasing number of CD83(+) TIDCs with longer relapse-free (p = 0.002) and overall (p < 0.001) survival. Furthermore, among patients with lymph node metastasis, the survival rate of those with larger numbers of CD83(+) TIDCs was significantly better than that of patients with fewer CD83(+) TIDCs. Multivariate analysis revealed that CD83(+) TIDCs had independent prognostic relevance in breast carcinomas. The infiltration of tumors by mature DCs expressing CD83 may be of great importance in initiating the primary antitumor immune response and is confirmed as an independent, immunologic prognostic parameter for survival in patients with breast cancer.     

Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma.

BACKGROUND: Axillary lymph node status has been the most important prognostic factor in operable breast carcinoma, but it does not fully account for the varied disease outcome. More accurate prognostic indicators would help in selection of patients at high risk for disease recurrence and death who are candidates for systemic adjuvant therapy. Our recent findings indicated that microvessel density (count or grade) in invasive breast carcinoma (a measure of tumor angiogenesis) is associated with metastasis and thus may be a prognostic indicator. PURPOSE: This study was designed to further define the relationship of microvessel density with overall and relapse-free survival and with other reported prognostic indicators in breast carcinoma. METHODS: In a prospective, blinded study of 165 consecutive patients, the microvessels within primary invasive breast carcinoma were highlighted by immunocytochemical staining to detect factor VIII-related antigen. Using light microscopy, we counted microvessels per 200x field in the most active areas of neovascularization and graded microvessel density. These findings were correlated, by univariate and multivariate analyses, with overall and relapse-free survival, axillary node status, and other prognostic indicators (median follow-up, 51 months). RESULTS: There was a highly significant (P < or = .001) association of microvessel density with overall survival and relapse-free survival in all patients, including node-negative and node-positive subsets. All patients with breast carcinomas having more than 100 microvessels per 200x field experienced tumor recurrence within 33 months of diagnosis, compared with less than 5% of the patients with breast carcinoma having 33 or fewer microvessels per 200x field. Moreover, microvessel density was the only statistically significant predictor of overall survival among node-negative women (P < .001). Only microvessel density (P < .001) and histologic grade (P = .04) showed statistically significant correlations with relapse-free survival in the node-negative subset. CONCLUSIONS: Microvessel density in the area of the most intense neovascularization in invasive breast carcinoma is an independent and highly significant prognostic indicator for overall and relapse-free survival in patients with early-stage breast carcinoma (I or II by International Union Against Cancer criteria). IMPLICATIONS: Such an indicator would be useful in selection of those node-negative patients with breast carcinoma who are at high risk for having occult metastasis at presentation. These patients could then be given systemic adjuvant therapy.     

Prognostic significance of vascular endothelial growth factor D in breast carcinoma with long-term follow-up.

PURPOSE: Expression of angiogenic and lymphangiogenic factors by tumors may influence the route of metastatic spread. The angiogenic factor vascular endothelial growth D (VEGF-D) is implicated in the development of lymphatic vessels and promotion of lymphatic metastases. The purpose of this study is to determine whether VEGF-D correlates with lymph node metastasis or prognosis. EXPERIMENTAL DESIGN: We assessed VEGF-D expression using immunohistochemistry in 105 invasive breast carcinomas with long-term follow-up. The relationship among VEGF-D expression, lymph node status, and other established clinicopathological parameters was assessed. Whether VEGF-D expression plays prognostic role in breast cancer was also investigated. RESULTS: VEGF-D expression was identified in 86 cases (81.9%). Positive VEGF-D was significantly correlated with lymph node metastasis (P = 0.0238) and high c-erbB-2 expression (P = 0.0211). Survival curves determined by the Kaplan-Meier method and univariate analysis demonstrated that positive VEGF-D was associated with both disease-free survival (P = 0.0023) and overall survival (P = 0.0222). In multivariate analysis using the Cox regression model, positive emerged as an independent indicator for disease-free survival (P = 0.0452). CONCLUSIONS: VEGF-D expression is associated with lymph node metastasis and may be a novel prognostic factor in breast cancer. VEGF-D may be useful in the treatment of breast cancer as a decision-making biomarker for aggressive treatment after operation.     

The use of Doppler ultrasound in evaluation of breast cancer metastasis to axillary lymph nodes

The formation of microvessels in tumors by angiogenesis is considered to be an important prognostic factor, and closely correlates with lymph node metastasis. We used color Doppler ultrasound to examine the relationship between the amount of blood vessels in tumors and pulsatility index (PI), and tumor size in breast cancers, with and without regional lymph node metastasis. Doppler ultrasound was performed on 80 patients with breast cancer prior to surgery. The concentration of vascular endothelial growth factor (VEGF) within the tumors was measured following surgery in 42 cases chosen at random. In the negative metastatic nodes group, the number of vessels in the tumor correlated positively with tumor diameter. In the positive metastatic nodes group, however, the number of blood vessels in the tumor did not correlate with tumor diameter. Differences in tumor vascularity between node positive and negative groups were useful in determining the status of node metastasis in subsequent analysis. Fifteen of 17 cases of tumors that measured <20 mm, and in which there were no blood vessels, were node-negative. There were no node-negative tumors measuring >20 mm in diameter (p=0.003). Conversely, in nodes with positive metastasis, blood vessels were observed in 5 of 7 tumors that measured <15 mm in diameter (p=0.019). These findings may be useful in estimating the likelihood of metastasis to regional lymph nodes. PI was directly proportional to tumor size in the negative nodes group (r=0.47). There was no such correlation in the positive nodes group. There was no correlation between VEGF concentration in the tumor and the number of blood vessels in that tumor. In conclusion color Doppler analysis of blood vessels appears to be useful in predicting lymph node metastasis, especially for small tumors.     

Tie2/Tek expression in breast carcinoma: correlations of immunohistochemical assays and long-term follow-up in a series of 909 patients

The degree of angiogenesis in breast cancer has previously been shown to be an indicator of prognosis, and tumor microvasculature is at present a candidate target for new antiangiogenic therapies. Tie2/tek receptor tyrosine kinase is a novel marker of microvasculature of solid tumors that appears to play a key role in the angiogenesis process in breast cancer. However the prognostic significance of Tie2 has never been demonstrated in this neoplasm. In order to establish the prognostic value of Tie2 in breast carcinoma, we investigated Tie2 expression in a large series of patients and correlated it with long-term follow-up. Tie2 expression was investigated using immunohistochemical assays with a polyclonal antibody on frozen sections in a series of 909 patients, and was correlated with long-term (median, 11.3 years) follow-up. Univariate (Kaplan-Meier) analysis showed that a large Tie2 positive tumor surface (cut off = 7%) was significantly correlated with poor overall survival (p=0.025). Tie2 expression correlated with high metastasis risk among all patients (p=0.00067) and among node negative ones as well (p=0.01). Tie2 immuno-expression was also significantly predictive of relapse in all patients (p=0.003) and in the node negative subgroup (p=0.02). In multivariate analysis (Cox model) Tie2 immunodetection was identified as an independent prognostic indicator. Our results suggest that Tie2 immunohistochemical expression exhibits practical clinical relevance in terms of prognostic prediction. Tie2 expression permits identification of poor outcome patients, in particular node negative ones with high risk of metastasis and relapse. Tie2 immunodetection may further be considered as a potential tool for selecting patients who could benefit in the future from specific antiangiogenic therapy interfering with Tie2 pathway.     

VHL和CD31-MVD在结肠癌组织中的表达及临床意义

目的:通过检测VHL和CD31标记的微血管密度(CD31-MVD)在结肠癌组织中的表达，探讨两者与结肠癌临床病理特征的相关性，从而了解VHL调控结肠癌发生发展的作用和机制。方法:收集结肠癌手术标本106例作为实验对象，应用免疫组化SP法检测VHL及CD31在结肠癌中的表达，分析VHL表达及CD31-MVD与患者临床病理特征之间的关系并分析二者相关性。结果:VHL在癌组织中的表达阳性率（46.2%）明显低于切缘正常组织（71.7%)(P<0.05）。VHL在结肠癌中的表达，与有无淋巴结转移、TNM分期相关（P<0.05），CD31-MVD在结肠癌中平均值24.50±4.54，与肿瘤最大径、有无淋巴结转移、TNM分期相关（P<0.05），与其他临床病理特征无关，且CD31-MVD与VHL的表达呈负相关。结论:VHL蛋白在结肠癌中呈低表达并和肿瘤转移、分期相关，VHL的表达缺失与结肠癌血管密度相关，并且可能通过调控血管生成影响结肠癌的生长及转移。     

Tumor angiogenesis in node-negative breast carcinomas — relationship with epidermal growth factor receptor,estrogen receptor,and survival

Summary Angiogenesis is essential for tumor growth and metastases. Studies in breast carcinomas suggest that microvessel quantitation as a measure of angiogenesis might be one of the most powerful prognostic tools available. Node negative breast cancer is a particular group for which better prognostic markers would be helpful. We therefore measured microvessel density in a series of well characterised node negative breast carcinomas to evaluate angiogenesis as a prognostic marker and assess its relationship to epidermal growth factor receptor (EGFR) and estrogen receptor (ER), which have previously been reported to be of value. 109 patients with a mean age of 55 years and a median follow-up of 25 months were examined. Vessels were immunohistochemically highlighted using an antibody to platelet endothelial cell adhesion molecule CD31, and microvessel density was quantified using a Chalkley point eyepiece graticule. No significant correlation was observed with patient age, tumor size, grade, ER, or EGFR expression. In a univariate analysis of survival, whereas ER expression was not a significant indicator of either relapse-free (RFS) or overall survival (OS), vascular count (VC) predicted both early RFS and OS (p=0.01 and p=0.028 respectively). Furthermore, in patients with ER positive tumors, a subgroup usually considered to have a good prognosis, there was a significant reduction in RFS and OS if tumors had high VCs (p=0.05 and p=0.002 respectively). A further statistically significant reduction in RFS (p=0.05) was observed for EGFR positive highly vascular tumors. In a Cox proportional hazard model, VC remained a significant prognostic indicator for both RFS and OS (p=0.04 and p=0.01) and conferred a 6.6 and 3.5 times respective increased risk of mortality and relapse. These findings suggest that quantitation of angiogenesis is an independent predictor of survival in node negative breast carcinomas, and due to these high hazard ratios might be more useful than other recently described prognostic markers in selecting patients who would benefit from adjuvant therapy.     

Breast carcinoma: vascular density determined using CD105 antibody correlates with tumor prognosis

Angiogenesis is essential for tumor growth and metastasis. There are conflicting reports as to whether microvessel density (IMD) in breast cancers is associated with prognosis. This could be due to the use of different antibodies to endothelial cell markers, variation in tissue pretreatment protocols, and nonstandardized counting methods. We have assessed the IMD in 106 breast carcinomas using a pan-endothelial marker, CD34, and a recently described mAb to CD105, which preferentially reacts with endothelial cell in angiogenic tissues. IMD values (separated as above or below median) for CD105 expression showed a statistically significant correlation with overall (P = 0.0029) and disease-free survival (P = 0.0362). In contrast, blood vessel counts using a panendothelial marker CD34 did not correlate with overall or disease-free survival (P = 0.2912 and P = 03153, respectively). When IMD values were subdivided into quartiles and assessed for their prognostic values, there was a statistically significant difference in the overall survival across CD105, but not CD34, values (P = 0.0017 and P = 0.7997, respectively) and also disease-free survival (P = 0.0431 and P = 0.5066, respectively). Further analysis of IMD values demonstrated that there were no deaths in the lowest quartile for CD105 and it differed from the other three quartiles. However, examination of clinical details of patients in the lowest quartile failed to reveal clustering of patients known to be associated with low-risk factors. Multivariate analysis confirmed that IMD values using CD105 were an independent prognostic factor. These results suggest that the ability to quantitatively distinguish between tumor neovascularization and preexisting vessels may be important in the assessment of tumor angiogenesis, but requires confirmation in a greater number of patients with a longer follow-up.     

乳腺癌组织中CD105 mRNA的表达及其临床病理意义

目的　探讨CD10 5mRNA在乳腺癌中的表达以及与乳腺癌临床病理特征的关系。方法以β actin基因为参照 ,应用逆转录聚合酶链反应 (RT PCR)技术 ,检测 4 0例乳腺癌患者的肿瘤中心处癌组织、肿瘤边缘癌组织及癌旁正常腺体组织中CD10 5的表达。应用条带密度分析软件TotalLabv2 .0 1,定量分析RT PCR产物电泳带密度。结果　肿瘤中心处癌组织中CD10 5mRNA的表达水平为 0 .4 4± 0 .10 ,明显高于正常腺体组织 (P <0 .0 5 ) ;肿瘤边缘处癌组织中CD10 5mRNA的表达水平为 0 .6 0± 0 .11,明显高于中心处癌组织 (P <0 .0 5 )。CD10 5mRNA高表达与淋巴转移有关 (t=2 .71,P <0 .0 5 ) ,而与患者年龄、癌肿的大小、临床病理分期和病理类型无关 (P >0 .0 5 )。结论　乳腺癌组织中CD10 5mRNA的表达水平明显高于正常腺体组织 ,且肿瘤边缘处癌组织表达最高 ,其表达与乳腺癌的发生、发展及淋巴转移有关。     

Expression and prognostic relevance of the death receptor CD95 (Fas/APO1) in renal cell carcinomas

CD95 (Fas/APO1) is one of the best known members of the death receptor family which can either mediate apoptosis or activate tumor-promoting pathways. Using a tissue microarray we investigated the association between the expression of CD95 and prognosis in 617 patients with renal cell carcinomas (RCCs). CD95 was expressed in the vast majority of RCCs. High CD95 expression was associated with lymph node metastasis and correlated negatively with disease-specific survival. Multivariate Cox regression analysis confirmed CD95 expression as an independent prognostic factor. In conclusion, high CD95 expression is a negative independent prognostic factor in RCCs which could be used to identify high-risk patients with a poor clinical prognosis.     

粘附分子CD44在乳腺癌中的表达及其意义

目的探讨粘附分子CD44在乳腺癌中的表达及其临床意义。方法采用逆转录聚合酶链反应(RT-PCR)方法对30例乳腺癌及1O例乳腺良性肿瘤组织中的CD44基因的表达进行检测。结果①CD44V6在乳腺癌中的表达显著性高于乳腺良性肿瘤;②乳腺癌组织中CD44V6表达率明显高于CD,S及CD44V3;③Ⅲ、Ⅳ期乳腺癌CD44V6表达显著高于Ⅰ、Ⅱ期乳腺癌;④有淋巴结转移的乳腺癌CD44V6的表达明显高于无淋巴结转移者。结论GD44V6在乳腺癌中的表达与乳腺癌的发生发展、浸润转移和预后密切相关,可作为临床判断浸润转移和估计预后的一个有价值的指标。     

Plasma levels of soluble CD105 correlate with metastasis in patients with breast cancer

CD105 (endoglin), a receptor for transforming growth factor (TGF) beta1 and beta3 in vascular endothelial cells, is highly up-regulated in blood vessels of tissues where neovascularisation occurs. It modulates endothelial-mesenchymal signalling and is essential for angiogenesis. Indeed, CD105 knock-out mice die from malvascularisation by 11.5 day p.c. In the present study CD105, TGFbeta1 and CD105/TGFbeta1 complexes were quantified in plasma samples from 77 healthy individuals and 92 patients with early stage breast cancer prior to any treatment. When compared with normal controls, both CD105 and CD105/TGFbeta1 complex levels were significantly elevated in breast cancer patients, whereas TGFbeta1 levels were lower in cancer patients. The most important finding to emerge was that CD105 levels were significantly increased in patients who developed distant metastasis compared with disease-free patients. While there was no significant difference between CD105 levels in controls compared to disease-free patients, it was significantly higher in patients with metastatic disease. Thus patients who had died following local relapse or distant metastases possessed the highest levels of CD105. Neither CD105/TGFbeta1 complex nor TGFbeta1 levels correlated with tumour progression. Our data indicate that CD105 might be a valuable novel angiogenic marker for identifying breast cancer patients who are at high risk of developing metastasis.     

CD151及CD163在乳腺癌组织中的表达及其临床意义

目的:研究乳腺癌组织中CD151与CD163的表达水平同时分析两个指标与乳腺癌临床病理参数及预后的关系。方法:使用免疫组化检测100例乳腺癌和30例正常乳腺组织中CD151及CD163（M2巨噬细胞标记物）的表达水平,使用SPSS统计学软件分别对CD151和CD163与乳腺癌的临床病理参数之间的关系和两者的相关性进行统计学分析。结果:CD151表达在乳腺癌细胞的胞膜及胞质,CD163表达在乳腺癌组织的间质,CD151与CD163的阳性表达率分别为70%（70/100）和67%（67/100）,与正常乳腺组织相比,差异具有统计学意义（P<0.001）。CD151的阳性表达与乳腺癌组织学分级、TNM分期、淋巴结转移、ER（-)、PR（-)、Her-2（+)显著相关（P<0.05）,CD163的阳性表达与肿瘤体积、乳腺癌组织学分级、TNM分期、淋巴结转移、ER（-)、PR（-)、Her-2(+)显著相关（P<0.05）,乳腺癌组织中CD151与CD163的表达呈正相关（r=0.701,P<0.001）,CD151与CD163双阳性乳腺癌患者具有更高的复发转移率（P<0.05）。结论:乳腺癌组织中CD151与CD163表达明显增高,并与不良的乳腺癌行为密切相关。因此,乳腺癌组织中CD151与CD163表达高低对判断乳腺癌的预后具有重要作用。     

Loss of CD55 is associated with aggressive breast tumors.

PURPOSE: CD55 is a complement regulatory protein expressed by cells to protect them from bystander attack by complement. CD55 is overexpressed on some tumor cell lines, and in colorectal carcinomas, it has been shown to be an indicator of poor prognostic. EXPERIMENTAL DESIGN: A large set of samples (480) from patients with primary operable breast cancer followed for 4-192 months were included in the present study. The prognostic significance of CD55 was then investigated in these tumors using an anti-CD55 monoclonal antibody (RM1) that we raised against a synthetic peptide and a standard immunohistochemistry method. RESULTS: Ninety-five percent of the breast carcinomas expressed CD55 (RM1) with intensity ranging from weak (51%) to strong (6%). High expression of CD55 was significantly associated with low-grade (grades 1 or 2; P = 0.001), lymph node negativity (P = 0.031), and good prognosis tumors (Nottingham Prognostic Index < 3.4; P < 0.001). Survival analysis showed CD55 overexpression was associated with a more favorable outcome and loss of CD55 being associated with poor survival (P = 0.001). Intensity of CD55 expression was significantly correlated (P = 0.002) with intensity of CD59 expression (as shown in a previous study) in these series of patients. CONCLUSIONS: In conclusion, we found that loss of both CD55 and CD59 in breast carcinomas is associated with a worse prognosis.