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L Andrac

Publications and source records attributed to L Andrac.

At least 19 recordsLinked to original sources

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.

Adult↗

E-cadherin and beta-catenin expression in breast medullary carcinomas.

The initial step of cancer invasion and metastasis is the escape of tumour cells from the primary site, involving disruption of normal cell-cell adhesion and E-cadherin (E-cad) and beta-catenin (beta-cat) down-regulation, as shown in various types of human malignancies including breast carcinomas. Medullary carcinomas are high grade and poorly differentiated tumours with syncytial typical pattern, and prognosis unexpectedly better than that in high grade breast carcinomas. In a series of 55 breast typical medullary carcinomas diagnosed according to the strict use of Ridolfi et al (Cancer 40: 1365-1385, 1977) criteria, E-cad and beta-cat were investigated using quantitative (SAMBA 2005 system) immunocytochemical assays on frozen sections. Results were compared to that obtained on paraffin sections and in a series (n=55) of grade 3 ductal carcinomas. It was shown that medullary carcinomas significantly (p<0.001) expressed more E-cad and beta-cat than grade 3 ductal carcinomas. E-cad and beta-cat correlated with high expression of P53, of c-erbB, and of Ki-67 antigens, and with lack of hormone receptors antigenic sites (p<0.001). It was concluded that favourable prognosis and syncytial pattern of typical breast medullary carcinomas likely results, at least partly, from a particular expression of cell-cell adhesion molecules, significantly limiting tumour growth and efficiently mastering the tumour cell dissemination, opposing to high proliferative activity (grade 3).

Adult↗

Prognostic significance of Nm23/NDPK expression in breast carcinoma, assessed on 10-year follow-up by automated and quantitative immunocytochemical assays.

The Nm23 gene has been described as an antimetastatic gene; in some studies, disease progression in patients with solid tumours is related to Nm23 protein expression, which can be detected by immunohistochemical procedures. Detection of Nm23-H1 protein in breast cancer may be relevant for the monitoring of patient therapy, provided that the technical procedures are reliable and cost-effective. The aim of the present study was to determine the prognostic significance of Nm23, assessed by quantitative immunocytochemical assays (Nm23 ICAs), under optimal technical conditions. Nm23-H1 ICAs were performed on frozen sections, using an automated immunoperoxidase technique (Ventana) and computer-assisted analysis of digitized colour microscopic images (SAMBA), in a series of 168 breast carcinomas. The results of automated quantitative ICAs were correlated with patients' follow-up (129 months). Nm23-H1 immunocytochemical expression in histological sections of tumours in which more than 3 per cent of the surface area was positively stained was significantly (0.012) correlated with longer metastasis-free survival in both node-positive and node-negative groups of patients (P = 0.032 and P = 0.036, respectively) (Kaplan-Meier log-rank test, NCSS 6.0.1 software). Nm23 expression (cut-point 3 per cent) did not, however, correlate with overall survival, or with the recurrence-free survival. In multivariate analysis (proportional hazards regression, Cox model), the prognostic significance of Nm23 in terms of metastasis-free survival was independent of tumour size and grade, and of histological grade, in the entire cohort of patients. It is concluded that Nm23 immunodetection is only of limited practical clinical relevance in breast carcinoma, even when assessed under optimal technical conditions.

Adult↗

Acute transverse myelitis and primary urticarial vasculitis.

We report the case of a 56-year-old man with severe normocomplementaemic primary urticarial vasculitis for 16 years. Nine and 11 years after the onset of the symptoms, he developed two severe neurological complications, seizure and transverse myelitis, that must be attributed to the vasculitis. Transverse myelitis has been reported in other systemic diseases, particularly lupus erythematosus, but this is the first case of transverse myelitis complicating urticarial vasculitis.

Acute Disease↗

VCAM (IGSF) adhesion molecule expression in breast carcinomas detected by automated and quantitative immunocytochemical assays.

Expression of vascular cell adhesion molecules (VCAM) in tumors is associated with endothelial cell activation and may facilitate adherence of carcinomatous cells to the vessel wall, promoting bloodborne metastases. Expression of VCAM was investigated in 202 breast carcinomas using automated (Ventana System) and quantitative (SAMBA image analyzer) immunoperoxidase staining of frozen sections. Positive VCAM immunoreactivity was observed in 83 tumors (41%) (mean immunostained surface, 12.4%; SD, 10.5). The mean area of immunostaining was correlated with clinical and pathologic prognostic indicators and with the immunohistochemical expression in tissue sections of various indicators of cell proliferation, metastatic potential, and drug resistance or sensitivity, evaluated according to the same method. There was no correlation of VCAM immunoreactivity with tumor size, type, or grade or with nodal status. Also, no significant correlation was observed between VCAM and MIB1/Ki67, p53, Bcl-2, E cadherin, CD44v, cathepsin D, CD31, P-gp, ER, PR, or pS2. However, VCAM immunoreactivity was significantly correlated with ELAM and VLA2 (P = .001) and VLAs (P = .008) expression. The results suggest that VCAM expression in breast carcinoma tissue sections is likely not a prognostic indicator. Its practical clinical relevance, if any, must be established by correlation with patients' outcomes and tumor sensitivity to drugs.

Adult↗

VLA2 integrin expression in breast carcinomas evaluated by automated and quantitative immunohistochemistry.

VLA2 is thought to be involved in the metastatic process in malignant tumours, in particular in carcinomatous cell adhesion to vessel basement membrane. VLA2 expression was immunohistochemically investigated in 204 breast carcinomas. Frozen tissue sections were probed with monoclonal anti-VLA2 using automated (Ventana ES 320 System) and quantitative (SAMBA 2005 image processor) immunoperoxidase. A positive anti-VLA2 immunoreaction was observed in 48 tumours (23.5%), within epithelial carcinomatous cells. The VLA2-positive surface in tumours varied from 3% to 20% (mean 8.75, S.D. 7.17) and was correlated with histoprognostic indicators and tumour expression of various antigens detected using the same method as that for VLA2. The results show that VLA2 immunoexpression was independent of the tumour size, grade, type and aneuploidy, and of the nodal status. VLA2 significantly correlated with ELAM, VCAM, VLA3 and P-glycoprotein (P-gp) (P < 0.01) and inversely correlated with cathepsin D (P < 0.001), but was independent of Ki67/MIB1, p53, bcl-2, c-erbB-2, E cadherin, CD44v, CD31, oestrogen and progesterone receptors' (ER, PR) antigenic sites and pS2. The exact role, if any, of VLA2 in tumour cell dissemination remains to be elucidated and the clinical relevance of VLA2 immunodetection in breast carcinomas requires further investigation of the correlation between VLA2 immunocytochemical expression and patients' outcome and response to chemotherapy.

Adult↗

Reduced E-cadherin immunohistochemical expression in node-negative breast carcinomas correlates with 10-year survival.

E-cadherin immunodetection was performed on frozen sections, using an immunoperoxidase procedure and with computer-assisted analysis of digitized colored microscopic images in a series of 179 breast carcinomas. Quantitative immunocytochemical assays were correlated with follow-up (129 months). The results showed that reduced E-cadherin immunocytochemical expression in tumors (cut point, 4%) significantly correlated with shorter overall survival in node-negative patients (Kaplan Meier log rank test). But E-cadherin immunostained expression (cut point, 4%) did not correlate with metastasis-free or recurrence-free survival. In multivariate analysis (Cox proportional hazards regression model), E-cadherin prognostic significance for overall survival in node-negative patients was independent of the tumor size, grade, and histologic type. The results suggest that reduced E-cadherin expression detected in optimum technical conditions (frozen samples and quantitative immunohistochemistry) is an independent indicator of poor survival in node-negative patients and may be clinically relevant for the treatment of patients with breast carcinomas.

Adult↗

Physiopathogenic investigations in a case of familial stiff-skin syndrome.

BACKGROUND: Stiff-skin syndrome (SSS) is a rare cutaneous syndrome characterized by stony-hard skin and limitation of joint mobility. Its cause is still unknown. OBJECTIVE: Biological investigations were performed in a new case of SSS. METHODS: Collagen production and DNA biosynthesis were studied from fibroblast culture. Proinflammatory cytokines (TNF-alpha, IL-6 and TGF-beta2) were measured in the patient's serum. Results were compared with pathological findings. RESULTS: Collagen production and DNA biosynthesis were normal whereas the level of circulating cytokines was high. Histological examination of the skin showed mild fibrosis in the dermis whereas the fascia was not thickened. CONCLUSION: Our clinical and biological findings suggest that in this case, cutaneous changes may be related to an inflammatory process rather than to a primary fibroblast defect or a fascial abnormality as previously hypothesized.

Collagen↗

bcl-2 automated and quantitative immunocytochemical assays in breast carcinomas: correlation with 10-year follow-up.

PURPOSE: bcl-2 protein is detectable in human cancers and may be involved in the response to antineoplastic drugs or endocrine therapy in breast carcinomas. In a previous study, we had developed optimal technical conditions for bcl-2 immunodetection. The aim of the present report was to determine the prognostic significance of bcl-2 expression in breast carinomas by the use of a similar immunocytochemical procedure. METHODS: bcl-2 immunocytochemical assays were performed on frozen sections by automated immunoperoxidase technique (Ventana) and computer-assisted analysis of digitized colored microscopic images (SAMBA) in a series of 170 breast carcinomas. The results of automated quantitative immunocytochemical assays were correlated with patient follow-up (120 months). RESULTS: Intense bcl-2 immunocytochemical expression in tumors (cutpoint, 15%) significantly correlated with longer disease-free survival and longer recurrence-free survival in the entire cohort of patients (P = .028 and P = .035, respectively) and also in node-negative subgroups of patients (P = .028 and P = .01; Kaplan-Meier long-rank test; NCSS 6.0.1 software). But bcl-2 immunostained surfaces (cutpoint, 15%) did not correlate with overall survival. In multivariate analysis (proportional hazards regression, Cox model), bcl-2 prognostic significance in terms of disease-free survival was only independent of the tumor size and grade and histoprognostic index (Nottingham prognostic index [NPI]). CONCLUSION: bcl-2 immunohistochemical expression is a significant indicator of favorable outcome only in terms of disease-free and local recurrence-free survival. However, bcl-2 expression in tumors is an independent weakly prognostic indicator in breast carcinomas. bcl-2 immunodetection assessed in optimal technical conditions (frozen samples, automation, quantitative analysis, scatter diagram cutoffs) may have some limited practical clinical relevance for the management of patients with breast carcinomas.

Adult↗

Immunoexpression of E-cadherin and beta-catenin correlates to survival of patients with hepatocellular carcinomas.

Expression of E-cadherin (E-cad) and -catenin ( -cat) was investigated immunohistologically in 91 cases of excised hepatocellular carcinomas. Immunodectection was altered in 56% of tumours for E-cad and in 30.8% for -cat. Downregulation of E-cad and -cat correlated with the size of tumours, and high nuclear grade, but only E-cad alteration correlated with the mitotic index. Alterations of E-cad and -cat expression correlated with survival. Although E-cad and -cat immunodetections were independent prognostic factors, their prognostic value was lower than that of current clinicopathological parameters.

Adult↗

ELAM selectin expression in breast carcinomas detected by automated and quantitative immunohistochemical assays.

ELAM is an E-Selectin adhesion molecule involved in the inflammatory process but it is also thought to potentially participate in the development of blood borne metastases, by facilitating tumour cell adhesion to vessels wall. ELAM expression in tumours was immunohistochemically investigated in 203 breast carcinomas. Frozen tissue sections were probed with monoclonal anti ELAM (Clone 1.2B6) using automated and quantitative immunoperoxidase systems. A positive anti-ELAM immunoreaction was observed in 113 tumours (57%). The mean surface of positive tumours varied from 3% to 50% (mean = 11.75%, SD = 8.7) and was correlated with histoprognostic indicators and tumour expression of various antigens detected according to the same method as ELAM. The results showed that ELAM immunoexpression was independent of the tumour size, grade and type and of the nodal status but significantly increased parallel to patients' age (p<0. 01). ELAM expression was independent of Ki-67/MIB1, anti-P53 and anti-Bcl2, anti-CD44v, anti-c-erbB-2, anti-CD31, anti-RE/RP, anti-PS2, and anti-VLA3 immunoreactions. But ELAM expression correlated with that of the VCAM vascular cell adhesion molecule (p=0.0004), VLA2 (p<0.0001), P-glycoprotein (p=0.025), and of Cathepsin D to a lower degree (p=0.06) and inversely correlated with E-cadherin (p=0.03). The results suggest that endothelial cell activation is independent of tumour cell proliferative activity and of stromal angiogenesis and that the precise role and regulation of ELAM in tumours remains to be elucidated. Also the clinical relevance of ELAM immunohistochemical expression requires further investigation and correlation with patients' follow-up.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Polycystic disease of the salivary glands: report of an attack of the submaxillary glands].

Bilateral dysgenetic polycystic disease of parotid glands is an extremely rare pathologic condition in which salivary parenchyma is partially replaced by multiple epithelial-lined cysts arising from intercalated ducts. Review of the fourteen cases published in literature shows that it affects nearly exclusively women with an history of asymptomatic progressive enlargement of almost always both parotid glands. We report here the first case, to our knowledge, of a polycystic disease involving both submandibular salivary gland in a man.

Cysts↗

[Prognostic value of E-cadherin expression in hepatocellular carcinoma].

Expression of E-cadherin (E-cad) was investigated immunohistologically in 91 cases of operated hepatocellular carcinomas. An alteration of E-cad immunodetection was found in 56% of tumours. These alterations were correlated with histopathologic features of prognostic value including tumour size (> 3 cm), high nuclear grade and mitotic index. Patients with down-regulated E-cad expression had statistically significant shorter survival than the others. Although E-cad immunodetection was an independent prognostic factor, the Cox multivariate analysis showed that its prognostic value was low when compared to other prognostic factors.

Adult↗

Diabetic mastopathy, complication of type 1 diabetes mellitus: report of two cases and a review of the literature.

The breast is not classically included among the organs damaged by diabetic complications. The first cases of breast lesions associated with Type 1 diabetes mellitus were only described in 1984. The disease, designated as diabetic or fibrous mastopathy, is benign but may clinically simulate breast carcinoma. Its frequency is difficult to evaluate, and its pathogenesis is not yet clearly understood. We report two cases of diabetic mastopathy, together with a review of the medical literature on this subject and a description of the main characteristics of the disease. Diagnosis is based on the clinical context (premenopausal women with longstanding Type 1 diabetes mellitus who develop a hard, painless, mobile lump on one or both breasts), radiology (dense glandular tissue on mammography and marked acoustical shadowing of sound waves on sonography), and histopathology (fibrosis and perivascular and periductal lymphocytic infiltration).

Adult↗

Automated and quantitative immunocytochemical assays of Nm23/NDPK protein in breast carcinomas.

A series for Nm23-protein immunodetection was investigated in human breast carcinomas. Frozen sections were processed by automated immunoperoxidase procedure, and immunoprecipitates in positive tumors were quantified by processing digitized microscopic images. Nm23 immunohistochemical expression in tumors was correlated with clinicopathological data and with intra-tumoral proteins also detected by automated and quantitative immunohistochemistry. A positive Nm23 immunoreaction was observed in 58% of tumors, within cell cytoplasm. Nm23 expression was independent of the patient's age, and of tumor size, type and grade, but an inverse relationship was observed between Nm23 expression and axillary-lymph-node metastasis. An inverse relationship was also observed between Nm23 and P-53, CD-31, cathepsin D, tenascin and P-gp immunohistochemical expressions. But Nm23 expression was independent of c-erb-B product, growth fraction (MIB1/Ki67), and immunohistochemical expression of hormone receptors/P-S2. The results suggest that the anti-metastatic nm23 gene may partly act upon the regulation of tumor-cell proliferation (correlation with P-53) and may have some effects on epithelial-cell/stroma interactions (regulation of extracellular-matrix protease and of angiogenesis) independently of hormone sensitivity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

E-cadherin quantitative immunocytochemical assays in breast carcinomas.

The reduction of E-cadherin expression, which is involved in the initial step of invasion and metastasis of cancer, was investigated in 218 human breast carcinomas. Quantitative immunohistochemical assays (ICAs) were performed on frozen sections. Quantitation was assessed by processing digitized microscopic images of immunoreactions using a computerized system of image analysis (SAMBA). The results were correlated with clinicopathological data and quantitative immunodetection of other molecules. E-cadherin expression was significantly (P < 0.001) stronger in ductal carcinomas than in lobular carcinomas and stronger (P < 0.01) in low grades than in high grades, but E-cadherin was independent of lymph node status and tumour size. Also an inverse significant (P < 0.01) relationship was observed between E-cadherin expression on tissue sections and positive immunoreactions with anti-P53, MIB1 (growth fraction), and anti-c-erb-B2 product. Conversely, strong positive and anti-E-cadherin immunoreactions correlated with strong positive anti-ER and anti-PR immunoreactions (P < 0.01). No relationship was observed between E-cadherin and the results of quantitative ICAs of cathepsin D, CD31, and P-glycoprotein, assessed on consecutive sections from the same frozen tissue samples. The results show that preserved E-cadherin expression correlates with high degree of tumour differentiation, low proliferative activity, and low expression of prognostic markers. The deregulation of E-cadherin is independent of other steps of tumour invasion, such as protease digestion of extracellular matrix and angiogenesis.

Adult↗

Automated and quantitative immunocytochemical assays of CD44v6 in breast carcinomas.

CD44 variants carrying sequences encoded by exon v6 are preferentially expressed in metastatic animal cancer cell lines. CD44v6 overexpression correlates tumor dedifferentiation and progression in some human carcinomas, but the relationship of CD44v6 overexpression with metastatic behavior of tumor observed in animal models is controversial, particularly in breast carcinomas. The discrepancies probably result from analytical bias. We investigated CD44v6 and CD44s expression in 218 frozen samples of primary breast carcinomas. Immunocytochemical procedure was performed under optimal technical conditions using commercially available 2F-10 monoclonal antibody (MAb), a microprocessor-controlled automated device (Ventana Medical Systems, Tucson, AZ), and quantitative evaluation of results by processing digitized-colored microscopic images (SAMBA, Grenoble, France). CD44v6 expression in tissue sections was shown to be independent of the patient age, tumor size, histological types and grades, and the lymph node status. CD44v6 expression was also independent of the expression of molecules endowed with poor prognostic significance detected by MAbs (anti-p53, anti-c-erb B-2 protein, MIB1) on consecutive sections. No significant relationship could be evidenced either between CD44v6 expression, and CD31 involved stromal angiogenesis and cathepsin D. Finally, CD44v6 was independent of markers of hormone dependence (estrogen and progesterone receptors, pS2) and of multidrug resistance (P-glycoprotein). Similar results were observed with anti-CD44s. We conclude that the true prognostic significance of CD44v6 overexpression still remains to be shown under rigorous technical conditions (frozen samples, well-documented MAbs, and optimal standardization of procedure using automation and quantitative analysis) providing data appropriate for further correlation with long-term patient follow-up.

Adult↗