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J Jacquemier

Publications and source records attributed to J Jacquemier.

At least 91 records · Page 5Linked to original sources

Expression of FGF and FGF receptor genes in human breast cancer.

The family of FGF growth factors is involved in several biological processes and might play an important role in tumorigenesis. We have studied the respective expression of 8 of the 9 characterized FGF genes, and of the 4 known FGF receptor genes, in a panel of 10 tumor-cell lines and 103 breast-tumor samples, using RT-PCR and Northern-blot analyses. FGF1 and FGF2 were expressed in almost all samples, while expression of FGF5, FGF6, FGF7, and FGF9 was more restricted. FGFR1, FGFR2 and FGFR4 were expressed at high levels in respectively 22%, 4% and 32% of tumors. FGFR3 expression was not detected. The transcript encoding an FGFR1 isoform with 2 immunoglobulin-like domains was the most prevalent.

Base Sequence↗

Characterization of the region of the short arm of chromosome 8 amplified in breast carcinoma.

Chromosomal region 8p11.2-p12 is consistently amplified in human breast cancer. We have constructed a 2.8 Mb YAC contig of this region, centered on the human Fibroblast Growth Factor Receptor 1 (FGFR1) locus and encompassing the Adrenergic beta 3 Receptor (ADRB3) locus. A smaller centromeric YAC contig spanning 1.4 Mb was also assembled, and included the Ankyrin 1 (ANK1) and Tissue-type Plasminogen Activator (PLAT) genes. Results from mapping of the contigs showed physical linkage of the ADRB3 and FGFR1 genes, which were colocalized within the same YAC clone and separated by about 900 kb, FGFR1 being in centromeric position. It also showed physical linkage of ANK1 and PLAT genes, which appear to be separated by a maximum of 700 kb. In parallel, several loci were mapped according to their amplification status in a large panel of breast tumor samples. The overall amplification pattern suggested a continuous amplicon with a core around FGFR1. Data from both the detailed physical map and the amplification status allowed to establish the following gene order, from telomere to centromere: ADRB3-D8S105-FGFR1-ANK1-PLAT-POLB. The precise localization and YAC cloning of the core of the amplicon will allow to isolate a putative oncogene involved in mammary carcinogenesis.

Base Sequence↗

Patterns of loss of heterozygosity at loci from chromosome arm 13q suggests a possible involvement of BRCA2 in sporadic breast tumors.

Loss of heterozygosity (LOH) at loci from chromosome 13 is frequently observed in breast cancer. Chromosome 13 contains at least two cancer genes, the well-characterized RB1 gene located at 13q14 and the breast cancer-susceptibility gene, BRCA2, recently localized to 13q12. To investigate the possible involvement of BRCA2 in sporadic breast tumors, we looked at LOH at eight microsatellite (CA)n markers distributed along chromosome 13 in a panel of 59 primary breast carcinomas. We show that some LOH does not include the RB1 locus and is associated with the BRCA2 gene region.

Alleles↗

[Conservative treatment of sub-clinical noninfiltrating cancers of the breast (102 EOA in situ, TONO)].

102 patients with sub-clinical intra ductal non invasive breast cancer (T0N0) treated by limited surgery and curative radiation therapy. Follow-up ranged from 2 to 10 years with a median follow-up of 59 months. The long term survival rate of this therapeutic approach, consisting of simple excision without any adjuvant treatment and radical mastectomy was close to 100%. The actuarial local recurrence rate was only 8.6% at 10 years (confidence interval: 4.6 to 12.6%), which strongly suggests that radiation therapy is active on multicentric foci. Salvage surgery could be performed in every case of local recurrence. The survival rate of in situ breast cancer (T0N0) treated by conservative radio-surgery is comparable to that of radical mastectomy, while cosmetic results and psychological impact appear to be better for the conservative technique (breast preservation rate = 91 to 96%).

Breast Neoplasms↗

Expression of the FGFR1 gene in human breast-carcinoma cells.

Fibroblast growth factors (FGF) constitute a family of at least 9 members which act through high-affinity tyrosine-kinase receptors encoded by 4 distinct genes. In humans, the FGFR1 gene is located in chromosomal region 8p12. Its amplification and expression were examined in a panel of 110 breast carcinoma samples by Southern- and Northern-blot analyses. FGFR1 was amplified in 9% and overexpressed in about 15% of the tumors studied. In situ hybridization experiments were performed on tissue sections of normal breast and tumors with a high level of FGFR1 expression. In both normal and tumoral tissues, FGFR1 RNA was detected in the epithelial cells. Overexpression of FGFR1 seems to be associated with small, well-differentiated diploid tumors.

Blotting, Northern↗

The Heregulin gene can be included in the 8p12 amplification unit in human breast cancer.

The Heregulin (HGL) gene, encoding a ligand for a member of the ERBB receptor family, is located at 8p12-p22, in or close to a region frequently amplified in breast carcinoma. Amplification of HGL was detected in three of 83 (3.6%) cases of breast tumors. No overexpression of the gene was observed in the amplified tumors. This and the low incidence of amplification suggest that HGL is not the key gene of the 8p12 amplification but may be used as a marker of large amplification units.

Breast Neoplasms↗

Optimization of immunohistochemical detection of ERBB2 in human breast cancer: impact of fixation.

In an attempt to standardize the immunohistochemical detection of ERBB2, we evaluated six normal breast samples and 58 breast carcinomas for (1) the effect of four different fixatives (Bouin's fluid, buffered formalin, alcoholic formalin, and methacarn), and (2) the sensitivity and specificity of eight commercially available antibodies. ERBB2 gene copy numbers and RNA transcripts were measured by Southern and Northern blot analysis in all samples. The BT-474 and MCF7 cell lines were processed in the same way as the tissue samples and used a s references of activation or the normal state of the ERBB2 gene, respectively. Complete concordance between immunohistochemistry and molecular biology was observed in 43/58 cases (74 per cent). However, fixation and processing protocols significantly affected the reactivity of the antigenic determinants. The most consistent results were obtained with NCLCB11 on frozen sections and with Tab250 on paraffin-embedded sections. For prospective studies, the use of alcoholic formalin in association with a highly specific antibody (Tab250, 9G6, NCLCB11, or OA-11-854) gave the best results. Methacarn appears to be a reliable fixative, but was studied in only 28 cases. For retrospective studies, the most important parameter to take into account is the sensitivity of the antibody. Thus, with Bouin's fixation, 3B5 was the only reliable antibody, whereas with buffered formalin, Tab250 gave the most consistent results. This study will help inter-laboratory comparisons, and in determining the prognostic significance of ERBB2 expression in breast carcinomas using a standardized methodology.

Antibodies, Monoclonal↗

Pelvic staging of advanced and recurrent gynecologic cancers: contribution of endosonography.

From January 1988 to December 1992, 106 patients with advanced gynecologic cancer were preoperatively explored by clinical examination (CE) and endosonography (ESG) under anesthesia and by computed tomography (CT). Sixty-one tumors were primary and 45 recurrent; the main locations were cervical (73 cases), ovarian (10 cases), and endometrial (8 cases). All the patients were operated. This prospective study compares the data from clinical and imaging examinations with the histologic findings and the surgical reports. Accuracy of the CE, ESG, cytoscopy, and CT was respectively 79, 90, 82, and 80% for vesical involvement (ESG versus CT: P < 0.05). For vesicovaginal septum extension, accuracy of ESG (92%) was statistically better than that of CE (80%) and CT (77%). Accuracy of the CE, ESG, and CT was respectively 93, 97, and 89% for rectal involvement (ESG versus CT: P < 0.02). For rectovaginal septum extension, accuracy of ESG (96%) was statistically better than that of CE (85%) and CT (85%). Endosonography is valuable in the assessment of regional staging of advanced gynecologic cancers. Since it is realized during the clinical examination under anesthesia, this low-cost procedure is easily performed and provided no discomfort to the patients.

Adult↗

p53 immunohistochemical analysis in breast cancer with four monoclonal antibodies: comparison of staining and PCR-SSCP results.

The expression of p53 protein was examined in a series of 136 primary breast carcinomas, 106 of which were analysed with a panel of four monoclonal antibodies (MAbs 1801, 240, DO7 and DO1). p53 expression was detected with at least one antibody in 40 tumours (38%), whereas only 15 tumours (14%) were positive with all four antibodies. Some variability in the immunostaining could be observed depending on the antibody used. This was noticeable both for the number of positive cells within a section and for the intensity of staining. We therefore selected a panel of 17 tumour sections (nine were highly positive, three with medium to low staining and five with low to negative staining), which we analysed by polymerase chain reaction-single-strand conformation polymorphism analysis (PCR-SSCP) for the presence of a p53 mutation at the molecular level. Mutations were identified in 15 cases. Therefore the proportion of p53-stained cells does not seem to be an exact representation of the number of cancer cells bearing a mutation within a tumour. A statistically significant correlation was observed between p53 expression, regardless of the number of positive antibodies, and grade III disease (P < 0.0001), oestrogen (P < 0.0001) or progesterone receptor negativity (P = 0.0061), increased Ki 67 index (P = 0.0018), epidermal growth factor receptor (EGFR) positivity (P = 0.0076) and aneuploidy (P = 0.037). No correlation was observed with tumour size or lymph node involvement. In univariate analysis p53 expression was not correlated with disease-free survival, in contrast to the classical prognostic parameters, which were statistically correlated. In this series p53 expression was not a marker of early recurrence.

Antibodies, Monoclonal↗

Unrestricted T-cell receptor V-region gene repertoire in tumor-infiltrating lymphocytes from human breast carcinomas.

BACKGROUND: Several lines of evidence indicate that a more favorable prognosis is correlated with the degree of lymphocyte infiltration within breast carcinomas. The characterization of these T-cell infiltrates appears necessary to explore the possible existence of an in situ immunologic response of the host against neoplastic cells. Previous studies have indeed suggested that the T-cell receptor (TCR) repertoire of tumor-infiltrating T-lymphocytes (TIL) should be restricted if they act specifically against tumor-related antigens. METHODS: To address this question, the expression of variable (V) region genes of the TCR-alpha and beta chains in intratumoral lymphocytes from five breast carcinoma biopsy specimens and one normal mammary gland specimen was analyzed using the polymerase chain reaction (PCR). The neoplastic samples included one medullary carcinoma and four ductal infiltrating carcinomas selected on the basis of a rich lymphoid stromal component. Primers specific for 18 different V alpha and 21 V beta families were used for PCR. RESULTS: In every case, TIL showed an unrestricted pattern of TCR V-region gene expression, similar to the repertoire observed in peripheral blood lymphocytes and in the normal breast tissue. CONCLUSIONS: According to these nonquantitative PCR experiments, the apparent lack of selection of a limited number of T-cell specificities in the affected tissues does not favor the existence of an in vivo lymphoid recruitment based on TCR recognition of neoplastic antigenic determinants. Further studies, however, leading to an accurate quantification of immunologically relevant T-cell clones and including larger series of cases still are necessary before it will be possible to draw a final conclusion.

Blotting, Southern↗

FGFRI and PLAT genes and DNA amplification at 8p12 in breast and ovarian cancers.

Several chromosomal regions are found to be consistently amplified in human breast cancers. For two of these regions, 8p12 and 10q26, we previously reported the amplification of genes encoding FGF receptors, FGFRI/FLG and FGFR2/BEK, in about 12% of breast tumors. The PLAT gene, encoding the tissue-type plasminogen activator, is also located close to or within the 8p12 region. In the present study, we show that both FGFRI and PLAT can be amplified in breast as well as ovarian carcinomas. FGFRI amplification was detected in 14.5% of breast and 7.8% of ovarian tumors, whereas PLAT was found to be amplified in 15.6% and 19.4% of the tumors, respectively. Each gene could be amplified independently of the other. These data raised the question of which gene is selected for amplification at 8p12. In most cases, the levels of expression of FGFRI and PLAT in breast tumors were comparable to their level of expression in normal mammary tissue. However, FGFRI was expressed above the normal level in a certain number of cases. This gene could be a good candidate as "driver" of the 8p12 amplification, but it cannot account for all complex molecular events taking place in this region.

Breast Neoplasms↗

Medullary carcinoma of the breast. A multicenter study of its diagnostic consistency.

Nine pathologists from different institutions reviewed in a double-blind study 16 breast tumors previously indexed as typical medullary carcinoma, atypical medullary carcinoma, or infiltrative ductal carcinoma. A set of 16 slides was circulated two times among the nine pathologists. The diagnoses of typical and atypical medullary carcinomas were based on a definition given by Ridolfi et al. The interobserver and intraobserver agreement was low, with a kappa value of less than .50. The only histological criterion that had more than 50% agreement was the presence or absence of an in situ component in the tumor, assuming that the disagreement of one pathologist is accepted. This study is a snapshot of the problems encountered in the diagnosis of typical medullary carcinoma in a routine context and it shows high levels of variations in diagnostic consistency.

Breast Neoplasms↗

Results of a prospective study with comparison of clinical, endosonographic, computed tomography, magnetic resonance imaging and pathologic staging of advanced gynecologic carcinoma and recurrence.

Between January 1988 and April 1991, 57 patients with advanced gynecologic carcinoma were preoperatively evaluated by gynecologic examination and endosonography (ESG) using general anesthesia. Abdominopelvic computed tomography (CT) was performed in 49 patients and magnetic resonance imaging (MRI) in 21 patients. There were 34 primary tumors and 23 instances of recurrence. Causes of gynecologic carcinoma were 38 carcinomas of the cervix uteri (26 primary and 12 recurrences), eight carcinomas of the ovary (four primary and four recurrences), three recurrences of carcinoma of the endometrium, five sarcomas of the uterus (one primary and four recurrences) and three primary carcinomas of the vagina. All of the patients were operated upon. This perspective study compares the data from clinical and imaging examinations to the data obtained from histologic examination of surgical sections. According to anterior or posterior tumor extension, the accuracy of clinical evaluation and preoperative imaging were studied for the posterior vesical wall and the vesicovaginal septum and the anterior rectal wall and the rectovaginal septum. Histologic examination revealed vesical involvement in 17 patients and of the involvement of vesicovaginal septum in 21 patients. The accuracy of the clinical examination, ESG, cystoscopy, CT and MRI was 83, 88, 87, 75 and 81 percent, respectively, for vesical extension. Cystoscopy was not taken into account for evaluation of extension to the vesicovaginal septum--accuracy was 80, 90, 67 and 86 percent for clinical examination, ESG, CT and MRI. Histologic examination showed involvement in the rectum in 14 patients and involvement in the rectovaginal septum in 19 patients. Rectoscopy was performed 13 times. The accuracy of clinical examination, ESG, CT and MRI was 91, 98, 89 and 71 percent, respectively, for extension to the anterior rectal wall. Rectoscopy was not taken into account for evaluation of extension to the rectovaginal septum--accuracy was 80, 96, 75 and 57 percent for clinical examination, ESG, CT and MRI. Endosonography would seem to be useful to complete examinations for regional extension of advanced gynecologic carcinomas. Its accuracy is superior to that of other examinations. Because it is performed using general anesthesia, there is no discomfort for the patient during this low cost procedure.

Cystoscopy↗

[Departmental compilation of histoprognostic data in senology. Apropos of campaign screening in Bouches-du-Rhône].

In January 1990 a registry for cases of breast cancer occurring in the Bouches-du-Rhone area was set up in conjunction with a screening programme for women over 50 years of age. The aim of this study was to compare histoprognostic findings of unscreened patients (A) with a palpable lesion, screened patients (B) with or without a palpable lesion and self screened patients (C) registered for clinically occult mammary carcinoma. The histoprognostic criteria studied were: histological type, tumor size, prognostic grade and axillary lymph node involvement. Of the 2,478 surgical procedures registered, 1,125 involved women over 50 years of age including 47% with malignant disease. Only 3.7% of screened patients presented intraductal carcinoma compared with 1.17% to 18.2% of unscreened A or self-screened C patients. The incidence of minimal infiltrating breast cancer smaller than 10 mm varied widely from 17.3% in A patients to 33.7% in B patients and 51.4% in C patients (P < 0.001). The incidence of histoprognostic grade III tumors ranged from 17.9% in A patients to 10% in B patients and 4.3% in C patients (P < 0.007). Lymph node involvement decreases from 41% in A to 28% in B patients and 23% in C patients (P = 0.01). Based on our data, 41.9% of screened patients were in the most favorable prognostic category, ie intraductal carcinoma or infiltrating carcinoma less than 10 mm or grade I and no lymph node involvement, versus only 26.1% of A patients and 60.9% of C patients (P < 0.0001). Information of the incidence, pathology of interval tumors in previously screened women will be evaluated in the future. This first study underscores the necessity for this kind of registry to evaluate the histoprognostic profile year by year of a breast cancer screening campaign.

Aged↗

Inflammatory carcinoma of the breast.

Inflammatory breast carcinoma has to be defined by accurate clinical and pathological criteria. The prognosis is very poor and improvements made by chemotherapy are limited to the increase in the disease-free period and overall survival for a few months.

Adult↗

Is breast conservation after local recurrence feasible?

The feasibility of conservative salvage surgery was addressed in a clinicopathologic study of the results of wide excision for 50 selected parenchymal intramammary recurrences after standard breast conserving treatment. After median follow-up of 51 months, 16 (32%) second local failures were observed (5-year local control 62%). Cox multivariate analysis of 18 parameters indicated that only disease-free interval and resection margins significantly influenced local control. 5-year local control was 92% for recurrences occurring after 5 years vs. 49% for shorter intervals, and 73% for negative vs. 36% for positive or indeterminate margins. Local control appeared independent of morphologic features, initial tumour stage, patient age, recurrent tumour size and location. Median survival after second local failure was 33 months; tertiary therapy obtained ultimate local-regional control in 8 of 16 cases. The authors conclude that wide excision is a particularly satisfactory alternative to salvage mastectomy for late recurrences. Negative margins are essential. Further study will be required to establish additional guidelines allowing improved patient selection.

Adult↗