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J Jacquemier

Publications and source records attributed to J Jacquemier.

At least 37 records · Page 2Linked to original sources
PubMed2001

WNT pathway and mammary carcinogenesis: loss of expression of candidate tumor suppressor gene SFRP1 in most invasive carcinomas except of the medullary type.

Secreted Frizzled-related protein 1 (SFRP1) encodes a member of a protein family that contains a cysteine-rich domain similar to the WNT-binding site of Frizzled receptors and regulates the WNT pathway. The WNT pathway is frequently altered in human cancers. We have defined the pattern of SFRP1 mRNA expression in the progression of breast cancer. We show that SFRP1 is expressed in the epithelial component of normal breast, in the in situ component of ductal carcinomas and is lost in more than 80% of invasive breast carcinomas except the medullary type. Loss of SFRP1 expression is correlated with the presence of hormonal receptors. Conversely, the maintenance of SFRP1 in carcinomas is correlated with the presence of lymphoplasmocytic stroma. No significant association was observed between SFRP1 status and the level of apoptosis in tumoral cells.

Adult↗
PubMed2001

Prognostic factors in localized primary synovial sarcoma: a multicenter study of 128 adult patients.

PURPOSE: To identify most significant and therapeutically relevant prognostic factors in adults with localized primary synovial sarcomas (SS) and to confirm the usefulness of the French Federation of Cancer Centers (FNCLCC) grading system, the prognostic impact of which has been already proven in soft tissue sarcomas. PATIENTS AND METHODS: Data on 128 patients with nonmetastatic SS collected from a cooperative database by the FNCLCC Sarcoma Group between 1980 and 1994 were studied retrospectively. Immunohistochemistry was performed at diagnosis in 77 cases (61%). The tumors were classified as biphasic (n = 45), monophasic fibrous (n = 72), and poorly differentiated (n = 10) subtypes. Histologic grade was determined according to the FNCLCC method, and vascular invasion was assessed in every case. RESULTS: The 5-year disease-specific survival (DSS) rate for this series of patients with localized SS was 62.9% (+/- 9.6% [SD]) with a median follow-up time of 37 months (range, 8 to 141 months). In multivariate analysis, the adverse risk factors associated with decreased DSS were International Union Against Cancer/American Joint Committee on Cancer stage III/IVA disease, male sex, and truncal tumor locations. For metastasis-free survival (MFS), disease stage III/IVA, tumor necrosis, and monophasic subtypes were the major factors associated with a less favorable prognosis. Separately, when not using disease stage, tumor necrosis, and mitotic activity, histologic grade became the most significant prognostic factor for both DSS and MFS. In addition, larger tumors and older patients become associated with a significantly worse prognosis. Independent adverse risk factors for local recurrence-free survival included histologic grade 3 and truncal tumor location. CONCLUSION: These data confirm that not all SS present the same severe outcome. High-risk patients identified on the basis of these parameters may qualify for an aggressive treatment approach.

Adult↗
PubMed2001

Tamoxifen and breast cancer risk in women harboring a BRCA1 germline mutation: computed efficacy, effectiveness and impact.

The management of breast cancer prone women remains a tough issue despite the release of institutional guidelines. Currently, only the anti-estrogen agent Tamoxifen and prophylactic surgery are claimed to decrease breast cancer incidence. However, efficacy of Tamoxifen, particularly in BRCA1 gene carriers, remains controversial and acceptability of prophylactic surgery is low. To evaluate the expected impact of Tamoxifen in preventing hereditary breast cancers, a modelling was made according to the efficacy of the treatment with respect to biological predictors of response: estrogen receptor (ER) and pS2 status of a series of 33 BRCA1-related breast cancers (BRCA1-BCs), and using data on BRCA1-BCs penetrance, as well as compliance and acceptability of the strategy. Although, 88% of BRCA1-BCs are ER negative in our series, 30% of cases are pS2 positive, implying a potential hormonal sensitivity of a proportion of these cancers. From our modelling, the expected impact of Tamoxifen in BRCA1 gene carriers is a reduction of breast cancer incidence of about 10% according to acceptability and compliance, close to that of 5% and of 13.5% for prophylactic mastectomy, according to acceptability rates from US and French surveys respectively. Since autonomy of choice is the root of western ethics, cancer prone women should be informed about the low but valuable expected reduction of incidence of breast cancer using Tamoxifen preventive therapy.

Antineoplastic Agents, Hormonal↗
PubMed2001

[Molecular typing of breast cancer: transcriptomics and DNA microarrays].

Breast cancer is the most frequent and deadly cancer of women. Its great heterogeneity makes prognosis and response to current treatments highly variable and difficult to predict. Mammary oncogenesis remains poorly understood. These issues should benefit from recent development of techniques capable of large-scale molecular analyses. The use of cDNA array techniques allows for the simultaneous analysis of the mRNA expression levels of thousands of genes in mammary tumor cell lines and breast tumors. Expression profiles will help classify tumors and provide new prognostic tools and potential therapeutic targets. They will also boost our knowledge of the molecular events responsible for the development and progression of this cancer.

Breast Neoplasms↗
PubMed2001

[Mammary carcinoma arising in microglandular adenosis: a case report].

Microglandular adenosis is an uncommon benign breast entity considered as a variant form of adenosis. The diagnosis is frequently made by the pathologist as it is often clinically asymptomatic. Carcinoma arising in microglandular adenosis is very uncommon. We report a case of carcinoma arising in microglandular adenosis in a 54-year-old woman. The immunohistochemical profile, especially S100 protein expression and absence of epithelial membrane antigen, was useful to recognize the microglandular adenosis and the carcinoma of alveolar architecture, while invasion was suggested by the basement membrane disruption highlighted with anti-collagen IV immunostaining. The good prognosis of carcinoma associated with microglandular adenosis points out the importance of distinguishing this lesion from other breast carcinomas.

Basement Membrane↗
PubMed2000

Gene expression profiling of primary breast carcinomas using arrays of candidate genes.

Breast cancer is characterized by an important histoclinical heterogeneity that currently hampers the selection of the most appropriate treatment for each case. This problem could be solved by the identification of new parameters that better predict the natural history of the disease and its sensitivity to treatment. A large-scale molecular characterization of breast cancer could help in this context. Using cDNA arrays, we studied the quantitative mRNA expression levels of 176 candidate genes in 34 primary breast carcinomas along three directions: comparison of tumor samples, correlations of molecular data with conventional histoclinical prognostic features and gene correlations. The study evidenced extensive heterogeneity of breast tumors at the transcriptional level. A hierarchical clustering algorithm identified two molecularly distinct subgroups of tumors characterized by a different clinical outcome after chemotherapy. This outcome could not have been predicted by the commonly used histoclinical parameters. No correlation was found with the age of patients, tumor size, histological type and grade. However, expression of genes was differential in tumors with lymph node metastasis and according to the estrogen receptor status; ERBB2 expression was strongly correlated with the lymph node status (P < 0.0001) and that of GATA3 with the presence of estrogen receptors (P < 0.001). Thus, our results identified new ways to group tumors according to outcome and new potential targets of carcinogenesis. They show that the systematic use of cDNA array testing holds great promise to improve the classification of breast cancer in terms of prognosis and chemosensitivity and to provide new potential therapeutic targets.

Adult↗
PubMed2000

Local and distant failures after limited surgery with positive margins and radiotherapy for node-negative breast cancer.

PURPOSE: To determine the outcome of patients with positive margins after lumpectomy for breast cancer and to address the issue of the relationship between local recurrences and distant metastasis in the absence of chemotherapy. METHODS AND MATERIALS: Among 3697 patients with primary breast cancer, we retrospectively analyzed 152 patients who had undergone conservative surgery with axillary dissection, had infiltrating carcinomas with positive margins, were node-negative, and received radiotherapy without chemotherapy. One-third received hormonal therapy. Endpoints were local failure and distant metastasis. Median follow-up was 72 months. RESULTS: Five- and 10-year recurrence-free survival were 0.80 and 0.71 respectively for local recurrences, and 0.85 and 0.73 respectively for metastasis. Infiltrating carcinoma on the margins was associated with early local relapse as opposed to intraductal carcinoma. Local and distant recurrences had similar patterns of yearly-event probabilities. Hazard of relapsing from metastasis was 2.5 times higher after a local recurrence. In the multivariate analysis, negative estrogen receptors (ER-)(p = 0.0012), histologic multifocality (p = 0.0028), and no hormonal therapy (p = 0.017) predicted local relapses, while ER- (p = 0.004) and pathologic grade (p = 0.009) predicted metastasis. Hormonal therapy did not prevent early local recurrences. CONCLUSION: In this population, reexcision is advisable for local purposes and because the data support the hypothesis that local and distant recurrences are tightly connected.

Adult↗
PubMed2000

VEGFc and VEGFR3 expression in human thyroid pathologies.

In vertebrates, vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are major determinants of angiogenesis. In adults, the interaction between VEGFc and VEGFR3 (previously FLT4) is more specifically involved in the biology of lymphatics. Using PCR amplification of reverse-transcribed mRNA, we studied the expression of the VEGFR3 (including its short and long forms) and VEGFc genes in 38 samples of various human thyroid pathologies. VEGFR3 mRNA was detected in all samples of adenomas, nodular goiters and focal goitrogenic alterations; in all samples of thyroid tissue from patients with auto-immune diseases; and in some samples of adenocarcinomas. VEGFc mRNA was detected in most samples. We studied expression of the VEGFR3 and VEGFc proteins in thyroid tumors using appropriate antibodies. Co-expression of VEGFR3 and VEGFc was observed in most samples.

Adenocarcinoma↗
PubMed2000

Major improvement in the efficacy of BRCA1 mutation screening using morphoclinical features of breast cancer.

A family history of breast and/or ovarian cancer is the main criterion used in screening BRCA1 gene carriers. However, ascertaining a patient's family history is a difficult task, which significantly restricts the use of this parameter in clinical practice. Alternative individual criteria that can be used to identity BRCA1 gene carriers would, therefore, be of great value. In this context, it was recently established that BRCA1-associated breast cancers (BRCA1-BCs) show a specific morphoclinical pattern. In multivariate analyses, the two most discriminant morphoclinical parameters available for establishing the BRCA1 status, in addition to an early age at onset, are estrogen receptor negativity (ER-) and poor tumor differentiation (TD3). Here we tested the efficacy of these two morphological parameters as BRCA1 mutation indicators and investigated their economic impact, in a population-based survey on a series of women who developed invasive breast cancer by the age of 35 years, regardless of their family history. A high rate of 28.6% of BRCA1 mutations was found to have occurred in the group of tumors with both ER- and TD3 versus only 3.6% in tumors with other profiles (P = 0.007; odds ratio, 10.8). When the sole criterion used was early onset by the age of 35 years, the mutation rate was found to be 8.6%. The resulting cost of testing only women with ER- and TD3 tumors worked out at 30% that of testing the whole population of women with cancer by the age of 35 years, and the sensitivity was found to be of 66%. Lastly, the family history of ER- and TD3 cases with a BRCA1 mutation was investigated retrospectively, and none of these cases was found to have a particularly extensive family history of breast and/or ovarian cancer. The use of these morphological features of BRCA1-BCs that are currently typed in clinical practice, therefore, provides a helpful and cost-effective tool for those making decisions about genetic screening. This strategy makes it possible to identify gene carriers who would be overlooked using current criteria.

Adult↗
PubMed2000

Prognosis of breast-carcinoma lymphagenesis evaluated by immunohistochemical investigation of vascular-endothelial-growth-factor receptor 3.

Very few studies have yet addressed the question of the existence and role of lymphagenesis in tumor growth; it is generally overshadowed by the greater emphasis placed on the blood vascular system. Monoclonal antibodies against vascular endothelial-growth-factor receptor 3 (VEGFR3) have been shown to provide a specific antigenic marker for lymphatic endothelium. By comparison with the microvascular count (MVC), we investigated the prognostic value of the microlymphatic count (MLC) in a series of 60 cases of 2-cm-diameter breast carcinomas. The mean value of MVC was 72.5 and of MLC, 40.5. There was no quantitative correlation between these 2 parameters. The MVC but not the MLC had a prognostic value in overall survival. Neither the MLC nor the MVC had any correlation with axillary-lymph-node invasion.

Biomarkers↗
PubMed2000

Causes of inconsistency in diagnosing and classifying intraductal proliferations of the breast. European Commission Working Group on Breast Screening Pathology.

It is now widely recognised that classifying ductal carcinoma in situ (DCIS) of the breast and diagnosing atypical ductal hyperplasia are associated with significant interobserver variation. Two possible reasons for this inconsistency are differences in the interpretation of specified histological features and field selection where morphology is heterogeneous. In order to investigate the relative contribution of these two factors to inconsistent interpretation of intraductal proliferations, histological sections of 32 lesions were sent to 23 European pathologists followed 3 years later by images of small parts of these sections. Kappa statistics for diagnosing hyperplasia of usual type, atypical ductal hyperplasia and ductal carcinoma in situ were 0.54, 0.35 and 0.78 for sections and 0.47, 0.29 and 0.78 for images, respectively, showing that most of the inconsistency is due to differences in morphological interpretation. Improvements can thus be expected only if diagnostic criteria or methodology are changed. In contrast, kappa for classifying DCIS by growth pattern was very low at 0.23 for sections and better at 0.47 for images, reflecting the widely recognised variation in the growth pattern of DCIS. Higher kappa statistics were obtained when any mention of an individual growth pattern was included in that category, thus allowing multiple categories per case; but kappa was still higher for images than sections. Classifying DCIS by nuclear grade gave kappa values of 0.36 for sections and 0.49 for images, indicating that intralesional heterogeneity has hitherto been underestimated as a cause of inconsistency in classifying DCIS by this method. More rigorous assessment of the proportions of the different nuclear grades present could lead to an improvement in consistency.

Breast↗
PubMed2000

Translocation and coamplification of loci from chromosome arms 8p and 11q in the MDA-MB-175 mammary carcinoma cell line.

Rearrangement and coamplification of the 8p12 and 11q13 chromosomal regions occurs in a significant proportion of breast cancers. It usually involves a complex hybrid structure in which the FGFR1 and CCND1 genes are amplified. We report here a different type of 8p12-11q13 rearrangement in the MDA-MB-175 mammary carcinoma cell line. This amplification contains the NRG1/HGL (from 8p12-21) and DOC4 (from 11q13) genes, encoding respectively a ligand for ERBB receptors and a stress-induced protein which is a mammalian ortholog of Drosophila Tenm/Odz. It has been shown previously (Wang et al, Oncogene 18: 5718-5721, 1999) that these two genes are rearranged and fused by a translocation event. This type of event was not found in 30 tumors tested that showed coamplification of the 8p12 and 11q13 regions.

Breast Neoplasms↗
PubMed2000

The pathology of familial breast cancer: histological features of cancers in families not attributable to mutations in BRCA1 or BRCA2.

Breast cancers arising in carriers of mutations in the breast cancer susceptibility genes, BRCA1 and BRCA2, differ histologically from each other and from breast cancers unselected for a family history. However, a substantial proportion of families with multiple cases of breast cancer is not attributable to these two genes (non-BRCA1/2 families). We have now characterized the pathology of 82 breast cancers from non-BRCA1/2 families. Breast cancers in non-BRCA1/2 families were of lower grade (P = 0.0018), showed fewer mitoses (P < 0.0001), less nuclear pleomorphism (P = 0.0014), less lymphocytic infiltrate (P < 0.0001), a lesser extent of the tumor with a continuous pushing margin (P = 0.004), a lesser extent of the tumor composed of solid sheets of cells (P = 0.0047), less necrosis (P = 0.002), and wereparison with BRCA2 tumors, non-BRCA1/2 tumors were lower grade (P = 0.017) and exhibited less pleomorphism (P = 0.01) and more tubule formation (P = 0.05). In comparison with control breast cancers unselected for a family history of the disease, non-BRCA1/2 tumors were of significantly lower grade (P = 0.001), showed less pleomorphism (P = 0.0002), and had a lower mitotic count (P = 0.003). The results indicate that non-BRCA1/2 breast cancers differ histologically from both BRCA1 and BRCA2 breast cancers and are overall of lower grade. They also suggest that non-BRCA1/2 breast cancers differ from nonfamilial breast cancers, but these differences may be attributable to various types of bias.

BRCA2 Protein↗
PubMed1999

Histological type and syncytial growth pattern affect E-cadherin expression in a multifactorial analysis of a combined panel of sporadic and BRCA1-associated breast cancers.

E-cadherin is a prominent factor in maintaining the epithelial architecture, and loss of its normal function is considered to be a key element in cancer invasion. In breast cancer, correlation between alteration of E-cadherin expression and histological type has been reported, but associations with other parameters remain uncertain. To refine these findings and to explore the biological significance of features thought to result from alterations of cell-to-cell adhesion systems, rare in sporadic cases but more frequent in BRCA1-associated breast cancers (BRCA1-BCs), we investigated E-cadherin expression by immuno-histochemistry in a combined panel of 214 breast cancers enriched in hereditary cases (176 sporadic cases and 38 BRCA1-BCs). Following multivariate statistical analysis using a logistic regression model, only 2 parameters were significantly associated with loss of E-cadherin expression: lobular histological type (p < 0.0001), in agreement with previous results, and syncytial growth pattern (SGP) (p = 0.01). The latter result provides a biological basis for SGP, the cardinal feature of medullary breast carcinoma.

BRCA1 Protein↗
PubMed1999

Novel indications for BRCA1 screening using individual clinical and morphological features.

Since there is a lack of common family profile among BRCA1-gene carriers, and since the risk of being a mutation carrier is not limited to women with a family history of breast or ovarian cancer, multivariate statistical analysis using the logistic-regression model was carried out, to discriminate between sporadic cases and BRCA1-breast cancers (BRCA1-BCs), especially when information about the family history of breast/ovarian cancer and ethnicity are irrelevant or unavailable, in order to offer specific medical treatment to this population. We examined 32 BRCA1-BCs selected at cancer genetic clinics and 200 consecutive controls without family history of breast cancer for age at onset and current morphological parameters. Following the multivariate analysis, 3 parameters only, namely, early age at cancer onset [odds ratio (OR) for each year = 1.16; p < 0.0001], estrogen-receptor negativity (OR = 5.7; p = 0.01) and poor differentiation (OR = 5; p = 0.03) were found significant factors for predicting BRCA1-carrier status. The expected impact in BRCA1 screening of our model was estimated using data on 5700 breast-cancer cases from a hospital-based registry. Only 50 and 15% of tumours with early age at onset below 35 years present one or the other 2 discriminant parameters respectively. Consequently, whereas the probability of finding a BRCA1 mutation is rated low (6.2%) when the sole criterion of early onset up to the age of 35 years is used, based on our model, in the sub-group of women with a tumor that is both estrogen-receptor-negative and poorly differentiated the mutation-detection rate is predicted to be above the 10% chance level recommended by the ASCO guidelines. This sub-group of women, representing about 1% of all breast-cancer cases in Western countries, consequently deserves to be tested.

Adult↗