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J Jacquemier

Publications and source records attributed to J Jacquemier.

At least 73 records · Page 4Linked to original sources
PubMed1998

Consistency achieved by 23 European pathologists in categorizing ductal carcinoma in situ of the breast using five classifications. European Commission Working Group on Breast Screening Pathology.

The increased detection of ductal carcinoma in situ (DCIS) by mammographic screening, the greater use of breast-conserving surgery, and the recognition that certain histological subtypes are associated with a greater risk of local recurrence has led to the formulation of several new classifications of DCIS in recent years. There are, however, no data concerning the degree of consistency with which these schemes can be applied by reasonable numbers of pathologists. Thirty-three cases of DCIS were thus examined by a working group of 23 European pathologists who categorized them using five recently published classifications: (1) that of the European Pathologists' Working Group based on differentiation (a combination of nuclear grade and cell polarization) with categories of poorly, intermediately, and well differentiated; (2) one based entirely on nuclear grade with categories of high, intermediate, and low, currently in use in the UK national and EC-funded breast screening programs; (3) the same classification in which only two categories, high nuclear grade and other, were used; (4) the Van Nuys system in which lesions are divided into high grade, non-high grade with necrosis and non-high grade without necrosis; and (5) a two-category classification based entirely on the presence or absence of comedo necrosis. Of the three systems with three categories, Van Nuys gave the highest overall kappa statistic of 0.42. Others gave similar values of 0.37 and 0.35 showing that assessing cell polarization in addition to nuclear grade neither improves nor worsens consistency. In all three systems, the middle category was associated with the lowest value for kappa. Of the two systems with two categories, that based on nuclear grade gave the highest overall kappa of 0.46 and that based on comedo necrosis the lowest of 0.34. The most robust histological features were thus high- and low-grade nuclei and necrosis as long as the latter did not involve the recognition of a comedo growth pattern. These values probably represent the maximum achievable, at least by reasonable numbers of pathologists in everyday practice. They are better than those previously reported for classification based entirely on architecture, but further improvement is needed.

Breast Neoplasms↗
PubMed1998

[Reproducibility of histoprognostic grades of invasive breast cancer].

In the framework of the quality assurance of the pathologists involved in the screening campaign it was proposed to test the reproducibility of the classical SCARFF, BLOOM and RICHARDSON (SBR) grade and the ELSTON-ELLIS grade (E-E) mentioned in the recent European recommendations. Twenty-four cases of invasive carcinoma were analyzed by 21 pathologists. Sixty-eight per cent agreement was obtained for the SBR grade and 69% for the E-E grade in the first round and vice versa in the second round. The mean value of the kappa test was 0.54 with SBR and 0.53 with E-E. The differentiation of the carcinoma was found to be the most reliable index (kappa score greater than 0.5), followed by the mitotic index (kappa score = 0.39 for SBR and 0.36 for E-E), and the nuclear polymorphism obtained the lowest score (kappa score ranging from 0.33 to 0.38). In our hands, the use of the E-E grade did not improve the reproducibility particularly for the mitotic index. Our results suggest however that the reproducibility may be improved by training.

Breast Neoplasms↗
PubMed1997

Genome-wide search for loss of heterozygosity shows extensive genetic diversity of human breast carcinomas.

Deletions of genomic regions involving tumor suppressor genes are thought to be important in the initiation and progression of breast cancer. We conducted a genome-wide search for deleted regions in a series of 75 human breast carcinomas by studying the allelic patterns of 184 microsatellite markers distributed over all chromosomes and looking for loss of heterozygosity (LOH). We identified 56 regions of consistent LOH. Strikingly, every tumor had a different set of deletions. To study this complexity, we applied a phylogenetic-like type of analysis. Each region was involved in a certain proportion of tumors, ranging from 20 to 62%; the most frequently involved regions were on chromosome arms 8p, 11q, 16q, and 17p. There was a correlation (P = 0.005) between the level of LOH and the size of the tumors. Tumors with a high level of LOH were also highly proliferative and had a high mitotic index.

Alleles↗
PubMed1997

Loss of heterozygosity in human breast carcinomas in the ataxia telangiectasia, Cowden disease and BRCA1 gene regions.

To appreciate the involvement of known or potential susceptibility genes in sporadic breast tumors, we have searched for chromosomal deletions by studying loss of heterozygosity (LOH) at 43 microsatellite (CA)n markers from human chromosomes 10, 11 and 17, in 115 unselected consecutive samples of breast carcinoma with particular emphasis on specific regions. No site of consistent LOH was identified on chromosome 10. Five regions of LOH were contained within bands q22-24 of chromosome 11 for which nearly 50% of the tumors had LOH at at least one marker. This region is thus a major site of deletion in breast cancer and several tumor suppressor genes seem to be involved. One of them may be the ataxia telangiectasia (ATM) gene which is located in one of the affected regions. Five regions of LOH, one of which is within the BRCA1 gene area, were recognized along chromosome 17. LOH at three of these regions were found in highly proliferative tumors. When combined with a previous study of chromosome 13 with emphasis on BRCA2 and Rb1 genes, this work allowed to distinguish a total of 12 regions of LOH, variably affected in breast tumors and correlated with prognostic parameters.

Alleles↗
PubMed1997

Predictive factors for complete removal in soft tissue sarcomas: a retrospective analysis in a series of 592 cases.

BACKGROUND AND OBJECTIVES: In order to specify the indications for conservative surgery and preoperative therapeutic approaches of soft tissues sarcomas (STS), we looked for the clinico-pathological parameters associated with the failure to obtain a complete removal (CRm) of the tumor. METHODS: We retrospectively analyzed a series of 592 cases of primary non-metastatic STS. Surgery was performed in 495 cases as a primary treatment and in 88 cases after chemo- or radiotherapy. Nine patients were treated by chemotherapy-radiotherapy. In a univariate analysis, 20 parameters were tested for their association with CRm. A multivariate analysis was then used to define the independent parameters linked to the achievement of a CRm. RESULTS: In the univariate analysis, 15 parameters were found to be linked to the achievement of a CRm. Three of them proved to be independent in the multivariate analysis: T in the TNM classification, tumor location, and tumor necrosis. By the combination of these risk factors, four groups of patients were defined, with respective rates of CRm of 97% (no factor), 95% (one factor), 70% (two factors), and 48% (three factors). CONCLUSIONS: The achievement of a CRm after surgery of STS depends not only on the accessibility of the lesion, but also on tumor aggressiveness, a reflection of which is necrosis. The detection of necrosis by imaging procedures may thus help predicting the resectability of tumors and defining the indications for neoadjuvant therapies, likely to broaden the use of conservative surgery.

Adolescent↗
PubMed1997

Variation of bcl-2 expression in breast ducts and lobules in relation to plasma progesterone levels: overexpression and absence of variation in fibroadenomas.

Some women with benign breast disease eventually develop breast cancer. The mammary gland undergoes tissue remodelling according to hormonal influences, involving a balance between quiescence, proliferation, and mechanisms of cell death. Proliferation and/or apoptotic events could therefore be investigated to help understand the mechanisms of benign lesion formation and identify mastopathies with a poor prognosis. bcl-2 expression was analysed by immunohistochemistry in 75 benign mastopathies. Protein levels were quantitated with an image analyser in various epithelial structures on frozen sections, including adenoses, fibroadenomas, ductal epithelial hyperplasias, cysts, and apparently normal surrounding lobules and ducts. bcl-2 levels were equivalent in apparently normal lobules and ducts, as well as in cysts and ductal hyperplasias. bcl-2 staining was significantly higher in fibroadenomas, known to be of lobular origin [mean = 10.1, quantitative immunochemistry score (QIC) arbitrary units (AU), n = 19], than in normal lobules (mean = 5.1 AU, n = 43, P = 7 x 10(-5). bcl-2 levels in normal lobules and ducts varied according to the menstrual cycle, being higher during the follicular than the luteal phase (P = 1.8 x 10(-2) and P = 1.7 x 10(-2), respectively). This was further supported by a statistical link (P = 5 x 10(-3) between high levels of circulating progesterone and weak bcl-2 staining in lobules and ducts. This progesterone-dependent variation was absent in fibroadenomas. No statistical correlation was found between bcl-2 expression and circulating levels of oestradiol, and follicle-stimulating or luteotrophic hormones. Although these are only preliminary results, they suggest an influence of progesterone on bcl-2 expression which might be lost in fibroadenomas. A hypothesis is proposed concerning the potential involvement of altered regulation of the apoptotic process in the formation of such benign lesions.

Breast Neoplasms↗
PubMed1997

Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma.

PURPOSE: Several histologic grading systems have been validated in soft tissue sarcomas (STS), but no system is currently accepted worldwide. The National Cancer Institute (NCI) and French Federation of Cancer Centers Sarcoma Group (FNCLCC) systems were examined comparatively in the same population of patients with STS to determine which system is the best prognosticator with regard to metastasis development and tumor mortality. PATIENTS AND METHODS: Four hundred ten adult patients with nonmetastatic STS were examined. Histologic grade was established according to the NCI and FNCLCC systems in each case. The prognostic value of both systems was examined using univariate and multivariate (Cox's model) analyses, and special attention was devoted to tumors with discordant grades. RESULTS: In univariate analysis, both the NCI and FNCLCC systems were of prognostic value to predict metastasis development and tumor mortality. In multivariate analysis, high-grade tumors, irrespective of the system used, size > or = 10 cm, and deep location were found to be independent prognostic factors for the advent of metastases. Tumor grade had a higher predictive value than size or depth, and higher prognostic weight was assigned to the FNCLCC grading system in Cox models. Grade discrepancies were observed in 34.6% of the cases. An increased number of grade 3 STS, a reduced number of grade 2 STS, and a better correlation with overall and metastasis-free survival within subpopulations with discordant grades were observed in favor of the FNCLCC system. CONCLUSION: The FNCLCC system showed slightly increased ability to predict distant metastasis development and tumor mortality. The use of this system to evaluate STS aggressiveness might be favored.

Adolescent↗
PubMed1997

[Modalities of reading of detection mammographies of the programme in the Bouches-du-Rhône. Results and costs 1990-1995].

In the Bouches du Rhône breast cancer screening programme, mammograms are read by two separate radiologists of different levels of training. All women with at least one positive reading are recalled for further assessment. During the first round, 3,477 of the 95,967 screenees were recalled by the first reader and 2,321 by the expert reader. The expert increased cancer detection by 15% and 45% of cancers detected by the expert were smaller than 11 mm. The marginal cost of double reading was 21,838 Francs per additional cancer detected. Double reading thus allowed for the detection of cancers of good prognosis which would have gone undetected by a single reader. Its cost seems justified by its impact on the effectiveness of the screening programme.

Aged↗
PubMed1997

[Intensive chemotherapy with autologous stem cell transplantation in ovarian cancers: analysis of 67 patients treated at the Paoli-Calmettes Institute and a review of the literature].

Despite important initial chemosensitivity, advanced ovarian cancer has a bad prognosis with a median survival of 20 to 30 months. These results might be better with intensive chemotherapy. We analysed 67 patients treated by intensive chemotherapy with autologous stem cell transplantation for advanced ovarian cancer at Institute Paoli-Calmettes between 1980 and 1994. Population was divided in two groups: salvage group (n = 30) for initial chemotherapy-refractory patients and consolidation group (n = 37) for sensitive patients. Several successive conditioning regimens were used, all based on alkylating agents. Principal toxicities were severe aplasia and mucositis. Four patients died from toxicity related to infection during strong immunosuppression. In salvage group, 9 out of 21 evaluable patients responded (43%), but duration of responses was short (median range of 5 months) and 2-year overall survival rate was 8% after transplantation. In consolidation group, 19 patients are alive and 15 are without disease progression with a median follow-up of 42 months (17, 161) after diagnosis. Five-year disease-free survival rate is 28% (median range of 35 months) and 5-year overall survival rate is 48% (median range of 41 months). Intensification does not seem to be long term beneficial for initial chemotherapy refractory patients, despite objective responses rate better than classical treatment. On the other hand, results seem better than conventional treatments in case of chemosensitive disease and should be confirmed prospectively in larger cohort of patients. Moreover, other research directions are open like intensification supported by hematopoietic growth-factors and peripheral stem cells, definition of best conditioning regimen, use of taxanes, and intensification in first line chemotherapy after initial surgery.

Adult↗
PubMed1996

Truncation at conserved terminal regions of BRCA1 protein is associated with highly proliferating hereditary breast cancers.

The existence of two subgroups of BRCA1-associated breast cancer (BC) families has been recently posited: the first with highly proliferating tumors, and the second composed of cases with a low proliferation rate. Our aim was to test whether the proliferation rate of BRCA1-associated breast cancers was affected by the site of the germ line mutation in the BRCA1 gene. We analyzed the distribution of the mitotic index, a histoprognostic grade component shown to segregate in families, matching for germ line mutation location in a series of 28 breast cancers from 20 kindreds. We observed a prevalence of highly proliferating tumors when the mutation occurs in the two terminal conserved domains of the BRCA1 protein, ie., in the amino and carboxyl termini (P = 0.0024). Our data provide evidence for a genotype-phenotype correlation and along with their strong conservation during evolution argue for the importance of these two regions in the control of mammary cell growth.

Alleles↗
PubMed1996

Germ line mutation at BRCA1 affects the histoprognostic grade in hereditary breast cancer.

Histoprognostic grade is a determinant parameter to select the initial therapeutic strategy in breast cancer. Our aim was to analyze the grade repartition in BRCA1-associated breast cancer (BC) and to explore the possible connections between grade and the BRCA1 gene function. We first compared 27 BRCA1-associated BCs from 14 families with 4,461 cases from an administrative district registry and 242 cases from a hospital-based registry, matching for grade and constitutive elements, and then considered their repartition in families. We observed a prevalence of grade 3 (P < 0.0001) in BRCA1-associated BC. This was attributed mainly to nuclear polymorphism (P < 0.0001), mitotic activity (P < 0.0001), and tubular differentiation (P = 0.0004), implying that BRCA1-associated BCs are highly proliferating tumors. Moreover, it is suggested that grade segregates as a genetic trait within families (P = 0.0015), and this was attributed to the mitotic index segregation only (P = 0.0005). Therefore grade, through its components, could be interpreted as the morphological translation of the BRCA1 germ line mutation. Thus, a genotype-phenotype correlation may exist between the type of mutation and the aggressiveness of the disease. These findings are bound to have an important impact in the care management of hereditary breast cancer at the individual and at the familial level and in the comprehensive approach of breast cancer development.

Adult↗
PubMed1996

Prognostic factors in adult patients with locally controlled soft tissue sarcoma. A study of 546 patients from the French Federation of Cancer Centers Sarcoma Group.

PURPOSE: To define the prognostic factors in adult patients with locally controlled soft tissue sarcoma (STS) and to determine which patients should be considered for adjuvant treatment. PATIENTS AND METHODS: Five hundred forty-six patients with a nonmetastatic and locally controlled STS, collected in a cooperative data base by the French Federation of Cancer Centers (FNCLCC) Sarcoma Group from 1980 and 1989, were studied. Histologic slides of all patients were collegially reviewed. Initial treatment consisted of complete tumor resection with amputation in only 4% of the patients. Adjuvant radiotherapy was administered to 57.9% and adjuvant chemotherapy to 31%. Relationships between tumor characteristics were analyzed, and univariate and multivariate analyses were performed using Cox models for the hazards rate of tumor mortality, development of distant metastasis, and strictly local recurrence. RESULTS: Unfavorable characteristics with an independent prognostic value for tumor mortality were: grade 3 (P = 3 x 10(-10)), male sex (P = 1.5 x 10(-5)), no adjuvant chemotherapy (P = 5.4 x 10(-5)), tumor size > or = 5 cm (P = 3.8 x 10(-3)), and deep location (P = 4.6 x 10(-3)). Unfavorable characteristics for the development of distant metastasis were: grade 3 (P = 4 x 10(-12)), no adjuvant chemotherapy (P = 6.4 x 10(-4)), tumor size > or = 10 cm (P = 9.8 x 10(-4)), and deep location (P = 1.3 x 10(-3)). For the development of local recurrence, the unfavorable characteristics were: no adjuvant radiotherapy (P = 3.6 x 10(-6)), poor surgery (local excision) (P = 2 x 10(-4)), grade 3 (P = 7.6 x 10(-4)), and deep location (P = 10(-2)). Grade, depth, and tumor size were used to define groups of patients according to the metastatic risk. Adjuvant chemotherapy was beneficial in terms of overall survival and metastasis-free survival in grade 3 tumor patients only. Despite worse characteristics concerning tumor depth, tumor-node-metastasis (TNM) and American Joint Committee (AJC)/International Union Against Cancer (UICC) classifications and grade in patients with adjuvant radiotherapy, the latter experienced significantly fewer local recurrences than patients with no radiotherapy. CONCLUSION: Grade, tumor depth, and tumor size could be used to select patients with a high metastatic risk, for which adjuvant chemotherapy could be beneficial.

Adolescent↗
PubMed1996

[Recommendations for the immunohistochemical evaluation of hormone receptors on paraffin sections of breast cancer. Study Group on Hormone Receptors using Immunohistochemistry FNCLCC/AFAQAP. National Federation of Centres to Combat Cancer/French Association for Quality Assurance in Pathology].

These recommendations regard the immunohistochemical evaluation of estrogen and progesterone receptors in paraffin sections of breast cancers. All the components of the procedure are dealt with: fixation, antigen retrieval, antibodies, controls, analysis and interpretation of immunostaining, report and quality assurance parameters. The purpose of these guidelines is to serve as a basis for standardization of techniques and results and to improve quality control.

Breast Neoplasms↗
PubMed1995

ras, p53 and HPV status in benign and malignant prostate tumors.

To study the role of ras, p53 genes and HPV virus (16 and 18) in the development of prostate cancer, we analyzed tissue sections from 27 patients affected with carcinomas (stages A to D) and from 24 patients with adenomas. Mutations of H, K and N-ras and p53 (exons 2-9) were studied by SSCP and DNA sequencing. Accumulation of p53 protein was studied by immunohistochemistry on tissue sections. Tumors were also analyzed for the presence of HPV16 and -18 sequences by PCR and DNA hybridization with sequence-specific oligonucleotides. No mutation was found in the three ras genes studied, either in carcinomas or adenomas. By SSCP analysis we identified p53 mutations in only 2 of 19 carcinomas studied, both in exon 7. Immunohistochemical results strongly correlate with the SSCP results: p53 protein was positive in tumors with p53 mutation but not in others; 32% of studied adenomas had detectable HPV16 DNA, while 53% of carcinomas were HPV16+. Among these I presented a p53 mutation. No HPV18 E6 sequence could be detected. Our data show that in prostate tumors from France, mutations of p53 and ras are rare events but that these tumors display detectable HPV16 DNA at a high frequency. The low incidence of p53 mutation, associated to a significant proportion of tumors showing HPV16 DNA, could suggest that in prostate cancer HPV16 infection could participate in p53 inactivation by E6.

Adenoma↗