Rates of Neoadjuvant Chemotherapy and Oncoplastic Surgery for Breast Cancer Surgery: A French National Survey.

BACKGROUND: The current retrospective study was intended to obtain up-to-date and comprehensive data on surgical practice for breast cancer throughout France, including neoadjuvant chemotherapy (NAC) and the more recent surgical techniques of oncoplastic surgery (OPS). METHODS: In June 2011, e-mail surveys were sent to 33 nationally renowned breast cancer surgeons from French public or private hospitals. The questionnaire focused on all the new cases of breast cancer treated in 2010. It included questions regarding surgical practices, with special emphases on NAC and OPS and other surgical characteristics. RESULTS: The overall response rate for the survey was 72.7 %. The total number of breast cancer cases from the survey was 13,762, which constitutes 26.2 % of the total incidence in 2010. Breast-conserving surgery (BCS) was performed for 71.0 % of the patients, and the results were similar throughout the types of practices. Of these patients, 13.9 % received OPS, either upfront or after NAC. Mastectomy was performed for 29.0 % of the patients, which is consistent with French official numbers. Among all patients, 16.3 % underwent surgery after NAC. CONCLUSION: To the authors' knowledge, there are no publications of national figures on NAC or OPS rates to date. They are convinced that this study offers real-life surgical care information on a large population and covers France's breast cancer surgical landscape. Mastectomy rates in France remain stable and consistent with those in other European countries. However, additional large-scale retrospective studies are required to confirm these figures and further explore NAC and OPS rates as well as surgical practice characteristics.

Validation of an immunohistochemical signature predictive of 8-year outcome for patients with breast carcinoma.

We recently reported that standardized quantitative immunohistochemical (IHC) assays allowed prediction of an adverse outcome among 572 node negative (N-) patients with breast carcinoma (BrCa). To further validate our prior findings, we repeated the IHC stains including a second series of BrCa diagnosed at Yale University. Tissue microarrays (TMAs) of two cohorts of patients with BrCa (418 Marseille University and 303 Yale University) were respectively investigated for IHC expression of 15 markers (HIF-1α, PI3K, pAKT, pmTOR, moesin, P21, 4(E) BP-1, P27, Ker5-6, pMAPKAPK-2, SHARP2, claudin-1, ALDH, AF6 and CD24). Quantitative measurements of immunoprecipitates densitometry assessed with an image analyzer were correlated with 8-year patients' outcome and compared in the two cohorts. The best predictive signature consisted of a combination of five markers that included HIF-1α, PI3K, claudin-1, AF6 and pAKT in N- BrCa. This combination permitted an accurate prediction of outcome in 92.34% (386/418) of N- patients in the first set (Marseille) and 89.8% (158/176) in the second set (Yale). The close results in both cohorts confirmed the validity of this original IHC signature predictive of prognosis in node negative BrCa. This validation suggests that in clinical practice, it would be possible with standardized kits (i) to identify patients with poor prognosis at diagnosis time, particularly in the N- BrCa subset, who would require more aggressive adjuvant therapy and (ii) to avoid useless expensive therapies and their side effects in N- patients with favorable prognosis.

A nomogram predicting the probability of primary breast cancer survival at 2- and 5-years using pathological and biological tumor parameters.

PURPOSE: Our objective was to develop a nomogram to predict individual overall survival (OS) for primary breast cancer, based on pathological and biological tumor parameters. METHODS: A retrospective study in a cohort of 180 patients with primary breast cancer was used to build the nomogram. Pathological factors and tumor proteases measured prospectively in primary tumors were used. A multivariate Cox proportional hazards model was used to explore the relationship with OS, and regression coefficients were used to build the nomogram. The nomogram was internally validated with 200 bootstrap re-samples. RESULTS: The final variables included in the nomogram comprised tumor size (P = 0.04), nodal pathological status (P = 0.01), estrogen receptor status (P = 0.04), urokinase plasminogen activator inhibitor-1 (PAI-1; P = 0.02), thymidine kinase (P = 0.03), and cathepsin D (P = 0.004). The predictive accuracy of the nomogram at estimating the probability of OS, at both 2 and 5 years, was respectively 0.874 and 0.832 before and after calibration. CONCLUSION: A nomogram to predict 2- and 5-year OS in BC, using histological and biological parameters was successfully developed. This prognostic tool should prove useful in decision-making and therapeutic research.

Hypoxia inducible factor 1alpha gene (HIF-1alpha) splice variants: potential prognostic biomarkers in breast cancer.

BACKGROUND: Hypoxia-inducible factor 1 (HIF-1) is a master transcriptional regulator of genes regulating oxygen homeostasis. The HIF-1 protein is composed of two HIF-1alpha and HIF-1beta/aryl hydrocarbon receptor nuclear translocator (ARNT) subunits. The prognostic relevance of HIF-1alpha protein overexpression has been shown in breast cancer. The impact of HIF-1alpha alternative splice variant expression on breast cancer prognosis in terms of metastasis risk is not well known. METHODS: Using real-time quantitative reverse transcription PCR assays, we measured mRNA concentrations of total HIF-1alpha and 4 variants in breast tissue specimens in a series of 29 normal tissues or benign lesions (normal/benign) and 53 primary carcinomas. In breast cancers HIF-1alpha splice variant levels were compared to clinicopathological parameters including tumour microvessel density and metastasis-free survival. RESULTS: HIF-1alpha isoforms containing a three base pairs TAG insertion between exon 1 and exon 2 (designated HIF-1alphaTAG) and HIF-1alpha736 mRNAs were found expressed at higher levels in oestrogen receptor (OR)-negative carcinomas compared to normal/benign tissues (P = 0.009 and P = 0.004 respectively). In breast carcinoma specimens, lymph node status was significantly associated with HIF-1alphaTAG mRNA levels (P = 0.037). Significant statistical association was found between tumour grade and HIF-1alphaTAG (P = 0.048), and total HIF-1alpha (P = 0.048) mRNA levels. HIF-1alphaTAG mRNA levels were also inversely correlated with both oestrogen and progesterone receptor status (P = 0.005 and P = 0.033 respectively). Univariate analysis showed that high HIF-1alphaTAG mRNA levels correlated with shortened metastasis free survival (P = 0.01). CONCLUSIONS: Our results show for the first time that mRNA expression of a HIF-1alphaTAG splice variant reflects a stage of breast cancer progression and is associated with a worse prognosis.See commentary: http://www.biomedcentral.com/1741-7015/8/45.

A signature predictive of disease outcome in breast carcinomas, identified by quantitative immunocytochemical assays.

Quantitative immunocytochemical assays of 1,200 breast carcinomas were assessed after construction of tissue microarrays. A total of 42 markers were evaluated for prognostic significance by univariate log rank test (mean follow-up, 79 months), using quantitative scoring by an image analysis device and specific software. Complete data were obtained for 924 patients, for whom 27 of the 42 markers proved to be significant prognostic indicators. Analysis of these 27 markers by logistic regression showed that 18 (cMet, CD44v6, FAK, moesin, caveolin, c-Kit, CK14, CD10, P21, P27, pMAPK, pSTAT3, STAT1, SHARP2, FYN, ER, PgR and c-erb B2), and 15 when ER, PgR and c-erb B2 were excluded, were 80.52% and 78.9% predictive of disease outcome, respectively. The immunocytochemical assays on 4 micron thick sections of fixed tissue are easy to handle in current practice and are cost-effective. Quantitative densitometric measurement of immunoprecipitates by computer-assisted devices from digitized microscopic images allows standardized high-throughput "in situ" molecular profiling within tumors. It is concluded that this 15 marker immunohistochemical signature is suitable for current practice, since performed on paraffin sections of fixed tumor samples, and can be used to select patients needing more aggressive therapy, since this signature is about 80% predictive of poor clinical outcome. Also, the markers included in the signature may be indicative of tumor responsiveness to current chemotherapy or suggest new targets for specific therapies.

Quantitative immunocytochemical profile to predict early outcome of disease in triple-negative breast carcinomas.

We aimed in this study at identifying prognostic immunohistochemical molecular signatures indicative of disease outcome, also relevant for development of new specific therapies, in triple-negative (ER, PR, c-erbB2- negative) breast carcinoma subtypes. We evaluated 42 markers in tissue micro-arrays from a series of 924 breast carcinomas including 184 triple-negative tumors using standardized quantitative immunocytochemical assays and correlated the data with patients' outcome (mean follow-up of 79 months). When 27/42 markers including basal-like markers first found to be individually significant for prognosis in a univariate analysis (log-rank test) in 924 tumors, were secondly evaluated in the triple-negative tumor subtype (184/924), eleven including maspin, P21, P27, PTEN, caveolin, EGFR, FAK, P38, pMAPK, STAT1 and CD10 were 89.2% predictive of disease outcome in logistic regression. When markers reported in the literature as expressed in basal-like subtype were evaluated in the 924 series, only eight (EGFR, CK14, moesin, caveolin, cMet, ckit, CD44v6, C10) were prognosis predictive in univariate analysis (log-rank test) and in logistic regression were predictive of disease outcome in 66.3% independently of ER, PR and c-erbB2 expression and in 72% in triple-negative tumor subset. The results suggest that the category of 'triple-negative' breast carcinomas does not exactly overlap the basal-like subtype, and that immunoprofiling of triple-negative tumors (not similar to that of basal-like tumors) may be helpful to select patients for more aggressive treatment and provides a basis for development of tailored therapy.

Overexpression of c-Met and of the transducers PI3K, FAK and JAK in breast carcinomas correlates with shorter survival and neoangiogenesis.

c-Met is responsible for cell motility and tumour spreading. c-Met expression and signal transducers reflecting c-Met functionality were investigated in breast carcinomas, in correlation with patient outcome and tumour vasculature. Tissue microarrays of 930 breast carcinomas were constructed, categorised according to patients' follow-up (4- to 10-year follow-up; median, 6.5 years). Standardised immunocytochemical procedures were performed using anti-c-Met, -PI3K, -FAK, -JAK, and -CD146, -FYN and an automated autostainer (Ventana). High-throughput densitometry measuring the extent of immunoprecipitates was assessed by image analysis (SAMBA). c-Met overexpression correlated with poor survival along with PI3K and FAK reflecting c-Met functionality and CD146 and FYN expression in endothelial cells. Automated quantification of immunocytochemical precipitates using image analysis was shown to provide an objective means of measuring cellular proteins that are potentially relevant for current practice in pathological diagnosis and for specific therapy combining inhibitors of both c-Met and downstream transducer pathways, and of tumour angiogenesis.

Poor prognosis in breast carcinomas correlates with increased expression of targetable CD146 and c-Met and with proteomic basal-like phenotype.

Genomic studies have led to new taxonomic classifications of breast carcinomas. Proteomic investigations using tissue microarrays have yielded complementary results and are useful in identifying potential molecular targets for specific therapies. Searching for new drug targets is particularly important for tumors of poor prognosis, such as breast tumors that lack estrogen receptors and HER2 amplification; in these tumors, certain molecules probably play a significant role in tumor spreading through the stromal microvasculature. We investigated 930 breast carcinomas categorized according to patients' survival (range of follow-up = 4-10 years; median follow-up = 6.5 years) using (1) automated immunohistochemical procedures (Ventana, Cedex, France) with tissue microarrays (Alphelys, Plaisir, France) and (2) quantification of immunoprecipitates assessed by automated image analysis densitometry (SAMBA, Meylan, France). Expression of c-Met and CD146 and that of signaling transducers PI3K, FAK, and FYN were compared in living and deceased patients. Expression of some proteins recently reported to be characteristic of basal cell carcinomas was also assessed, namely, CK5-6, caveolin-1, carbonic anhydrase IX, p63, and CD117; these also constitute potential targets for therapies for aggressive tumors. Overexpression of these proteins was observed in deceased or metastatic patients (P < .01 to P < .00001), particularly node-negative patients (except for FYN, p63, and CD146). c-Met and CD146 are involved in tumor spreading, and our results suggest that they probably play an important role in patients' death, along with other proteins involved in hypoxia (carbonic anhydrase IX) and other cell functions or structures (caveolin-1, CD117, CK5-6, and p63) that are expressed in an aggressive subtype of basal cell carcinoma for which no specific therapy is available.

[High-throughput quantification of tissue microarrays: identification of candidate target proteins in inflammatory breast cancer]. / La lecture automatisée à haut débit des micro-biopsies en pathologie: mise en évidence de la surexpression de c-Met et PI3K dans les cancers du sein inflammatoire.

Inflammatory breast carcinoma (IBC) is a rare but very aggressive tumour phenotype. Increased c-Met protein expression correlates with reduced survival and a higher metastatic risk in many human malignancies, including breast cancer Several studies have shown that c-Met protein is targetable by specific drugs. Here we compared c-Met expression in IBC (n = 41) and non IBC (n = 480). Two microarrays of IBC and non IBC tissues were constructed and standardized. C-Met, P13K and E-cadherin were immunodetected (Ven-tana Benchmark Autostainer) on serial sections. The results were quantified with an automated image analysis device (SAMBA Technologies) by immunoprecipitate densitometry of each core section (0.6 microns thick). We found that (i) c-Met is significantly overexpressed in IBC compared to non IBC (p < 0. 001), (ii) P13K is also overexpressed (p < 0.001) in IBC, suggesting that overexpressed c-Met is functionally active, at least through the PI3K signal transduction pathway ; and (iii) E-cadherin is paradoxically overexpressed in IBC. We conclude that c-Met may constitute a target for specific therapy in patients with poor-prognosis malignancies like IBC Automated image analysis of TMA is a valuable tool for high-throughput quantification of the immunohistochemical expression of the tumor proteome.

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.

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.

Conservative treatment of cervical intraepithelial neoplasia using a cold-knife section technique.

OBJECTIVE: The purpose of this study was to evaluate a conservative cold-knife section technique for treatment of cervical intraepithelial neoplasia (CIN). This procedure can be adapted to patient age, preservation of childbearing potential and extent of dysplasia. DESIGN: Prospective study. SETTING: Gynecological Oncology Department in French Public Hospital. POPULATION: A total of 460 women treated for CIN between 1985 and 1999 were included. METHODS: A conservative cold-knife cervical section followed by blanket suture reconstruction was used in all cases. MAIN OUTCOME MEASURES: Immediate operative results, recurrence and reproductive function were assessed. RESULTS: The mean length of the cervical specimen was 11.4 mm (range, 4-22 mm). Mean specimen thickness was strongly correlated with age: 10.6 +/- 4.1 mm in women <40 years versus 12.1 in women >40 years; p < 0.001. Complete excision was achieved in 395 cases (85.8%). Post-operative bleeding was observed in 5 cases (1.1%). The mean duration of follow-up was 62 months (range, 12.3-156.5 months). Recurrences developed in 26 patients (6.6%) including CIN 1 in 9 cases, CIN 2 in 9 and CIN 3 in 8. No patient developed carcinoma. The actuarial risk of recurrence was 2.4% (+/- S.D., 0.9) at 24 months and 7.8% (+/-S.D., 1.9) at 60 months. A total of 52 pregnancies were observed in 39 patients. No case of de novo infertility was reported post-operatively. Amenorrhea was noted in 1 patient (0.1%) and dysmenorrhea in 1 patient (0.1%). CONCLUSIONS: This conservative cold-knife section technique is effective for treatment of CIN with low morbidity and little adverse effect on childbearing potential. Exposure of the squamocolumnar junction (SCJ) greatly facilitates follow-up.

Outcome of Epstein-Barr virus-associated primary breast cancer.

The presence of the Epstein-Barr-virus (EBV) has been reported to be a pathogenic factor in breast cancer (BC). We previously demonstrated the aggressiveness of EBV-positive BC. The purpose of the present study was to evaluate the effect of EBV on the prognosis of BC according to the BC phenotype. A total of 117 patients with primary BC previously tested for the presence of EBV were evaluated. The presence of the virus was evaluated in breast specimens using quantitative PCR (qPCR). Disease-free survival (DFS) and overall survival (OS) were evaluated for 4 molecular subtypes, namely luminal A and B (lumA and lumB, respectively), human epidermal growth factor receptor 2 (HER2) and triple-negative (TN) subtypes and according to the EBV status. EBV positivity was observed in 32.5% of the cases. TN, HER2 and lumB tumours were more frequent among EBV-BC cases (P=0.02). The DFS rates were different between BC subtypes (P=0.002), but the differences were not statistically significant when the cases were stratified according to the EBV status (P=0.08 for EBV-negative and 0.06 for EBV-positive cases). The OS rates were similar for BC subtypes (P= 0.50) and when the cases were stratified according to the EBV status (P=0.16 and P=0.67 for EBV-positive and -negative cases, respectively). EBV was not associated with DFS or OS, in contrast to BC phenotypes, tumour size or nodal status. Therefore, EBV positivity was found to exert no effect on survival, despite its association with aggressive BC phenotypes.

Post-operative nomogram for predicting freedom from recurrence after surgery in localised breast cancer receiving adjuvant hormone therapy.

PURPOSE: To develop a prognostic nomogram to predict freedom from recurrence for patients treated with adjuvant hormonal therapy (HT) for localised breast cancer (BC). METHODS: We performed a retrospective analysis of 142 patients treated with adjuvant HT between 1996 and 2000. Clinical and pathological parameters were analysed. RESULTS: A nomogram that predicts the probability of remaining free of recurrence for 5 years after surgery with adjuvant HT was developed using a Cox proportional hazards regression model. The progesterone receptor status (p < 0.001), nodal status (p = 0.008) and cathepsin-D (p < 0.001) were retained to construct the nomogram (C-index 0.734). CONCLUSIONS: The nomogram we developed may be useful for estimating the probability of successful treatment 5 years after surgery for localised BC.

Prognostic significance of angiogenesis evaluated by CD105 expression compared to CD31 in 905 breast carcinomas: correlation with long-term patient outcome.

Our purpose was to determine the respective prognostic significance of CD105 and CD31 immunoexpression in node negative patients with breast carcinoma, since angiogenesis induces blood borne metastases and death in carcinomas. CD105 (endoglin) has been reported as expressed by activated endothelial cells and consequently should better reflect neoangiogenesis in malignant tumors. Comparison of CD31 and CD105 immunocytochemical expression was undertaken in a series of 905 breast carcinomas. Results were compared to patients' long-term (median = 11.3 years) outcome. Univariate (Kaplan-Meier) analysis showed that the number of CD105+ microvessels (cut-off 15 vessels) correlated significantly with poor overall survival (p=0.001). This correlation was less significant in node negative patients (p=0.035). The number of CD31+ microvessels (cut-off 25 vessels) similarly correlated with poor survival (p=0.032) but not in the subgroup of node negative patients. Marked CD105 expression also correlated with a high risk for metastasis in all patients (p=0.0002) and in the subset of node negative patients (p=0.001). Similarly metastasis risk in node negative patients correlated with marked CD31 immunocytochemical expression (p=0.02). Multivariate analysis (Cox model) identified CD105, but not CD31 immunoexpression, as an independent prognostic indicator. Our results suggest that: i) in breast carcinomas, immunoselection of microvessels containing activated CD105 labelled endothelial cells is endowed with a stronger prognostic significance, as compared to CD31 vessels labelling; ii) the CD105 immunoexpression may be considered as a potential tool for selecting node negative patients with a poorer outcome and higher metastasis risk; iii) in these patients specific antiangiogenic therapy targeted by anti-CD105 conjugates can be further developed.

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.

Long-term prognostic significance of neoangiogenesis in breast carcinomas: comparison of Tie-2/Tek, CD105, and CD31 immunocytochemical expression.

The immunocytochemical detection of Tie-2/Tek, CD105, and CD31 was assessed in a large series (n = 905) of breast carcinomas on frozen sections. Results were correlated with patients' long-term outcome (median, 11.7 years) to define the respective prognostic significance of these markers. Univariate (Kaplan-Meier) analysis demonstrated that higher expression of CD31 (P = 0.032), CD105 (P = 0.001), and Tie-2/Tek (P = 0.025) correlated with poorer survival. However, only greater CD105 expression could significantly (P = 0.035) identify node-negative patients with poorer survival. Moreover, in multivariate analysis, CD105 and Tie-2/Tek, but not CD31, expression proved to be independent significant prognostic indicators. Marked expression of CD31 (P = 0.024), CD105 (P = 0.001), and Tie-2/Tek (P = 0.01) also correlated with higher risk of metastases in node-negative patients. It is concluded that CD105 immunoexpression in breast carcinomas is an independent prognostic indicator in node-negative patients, better in terms of overall survival than Tie-2/Tek and CD31. Also, Tie-2/Tek expression proved more sensitive than CD31 expression in terms of prognostic significance. Compared with CD31, CD105 and Tie-2/Tek have more clinical relevance for patient monitoring and also can serve as targets for specific therapy, such as CD105 immunotoxins or Tie-2/Tek pathway blockade, as recently suggested in experimental studies.

CD105 expression is a marker of high metastatic risk and poor outcome in breast carcinomas. Correlations between immunohistochemical analysis and long-term follow-up in a series of 929 patients.

CD105 (endoglin) is expressed significantly in activated endothelial cells in culture and in tumor microvessels. Quantification of CD105 immunocytochemical expression that may be clinically relevant has not been accurately evaluated. We studied CD105 expression on frozen tissue sections by using immunohistochemical assays in a series of 929 patients and correlated the findings with long-term follow-up (median, 11.3 years). Univariate (Kaplan-Meier) analysis showed that the number of CD105+ microvessels (cutoff, 15 vessels) correlated significantly with poor overall survival among all patients (P = .001). This correlation was less significant in node-negative patients (P = .035). Marked CD105 expression also correlated with a high risk for metastasis among all patients (P = .006) and among node-negative patients (P = .001). Multivariate analysis (Cox model) identified CD105 immunodetection as an independent prognostic indicator. Our results suggest that immunohistochemical expression of CD105 has practical clinical relevance for identifying node-negative patients with a poor prognosis. Moreover, immunodetection of CD105 also may be considered a potential tool for selecting patients who could benefit from specific antiangiogenic therapy, using anti-CD105 conjugates.

[Antecedents of cytological screening among patients treated for invasive cervical neoplasm]. / Antécédents de dépistage cytologique chez les patientes traitées pour cancer infiltrant du col de l'utérus.

OBJECTIVE: The aim of this study is to evaluate if the seriousness of invasive neoplasms of the uterin cervix actually observed is related to the apparition of rapid onset cases. POPULATION: 219 invasive cancers of the cervix treated from 1988 to 1999 in a gynecological oncologic department. METHODS: prognostic factors of cancers have been studied and compared to those of cases treated between 1975 and 1980 in the same department. The existence of cytological screenings has been searched and results have been analysed. RESULTS: Cervical cancers treated during the last 12 years have more serious prognostic factors than those treated during the former period. This evolution is shown by a progression of advanced stages of + 10.2%, an increase of lymph node invasion in proximal stages of + 13,4% and the doubling of number of adenocarcinomas. Though no change of the natural history of cancers has been proved. Only 42% of patients had profited of a cervical screening and cancers diagnosed at "stage I" are statistically more numerous in this group. Improvement should be brought up in the quality of samplings and of the care of abnormal results of cytological screening.

[Accuracy of intraoperative frozen section diagnosis in non palpable breast lesions: a series of 791 cases]. / Efficacité de l'examen peropératoire des lésions infracliniques mammaires: études sur une série de 791 cas.

The aim of this study is to estimate the accuracy and reliability of intraoperative frozen section of nonpalpable breast lesions. In fact, frozen section of palpable breast lesions has proven to be valid, but its use in breast infraclinic lesions has been discussed recently, with the publication of European recommendations. Diagnosis on frozen section was routinely performed in a serie of 791 patients with nonpalpable mammographically detected abnormalities breast lesions from January 1990 through July 2000. The initial frozen section diagnoses with known mammographic pattern were compared with the diagnoses obtained on permanent paraffin sections to estimate the accuracy of frozen sections. Frozen section diagnosis was delayed until final diagnosis assessed on permanent paraffin sections in only 8 cases (1%). Frozen section diagnoses were accurate in 744 of 783 cases (95%). The diagnosis was modified on the basis of permanent sections in 39 cases; consisting of 39 false negative. No false positive diagnosis was noted. Sensitivity and specificity of frozen section diagnoses were 87,69 and 100, respectively. When the comparison between frozen and permanent section was analyzed according to the mammographic pattern, the sensitivity among patients with microcalcifications was lower (75,23) than among patients with opacities (93,86). When frozen section and permanent section diagnoses were related according to the mammographic size ( 10 mm) the sensitivity among patients with opacities measuring less than 10 mm was lower (91,75) than among patients with opacities larger than 10 mm (95,65) and the sensitivity among patients with microcalcifications larger than 10 mm was greater (77,14) than among patients with microcalcifications size less than 10 mm (74,28). This results are similar to those obtained on palpable breast lesions, and show that frozen section is a feasible and reliable procedure in nonpalpable breast lesions, particularly more relevant in mammographic opacities than in microcalcifications, whatever the lesion size.