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X Sastre-Garau

Publications and source records attributed to X Sastre-Garau.

At least 19 recordsLinked to original sources
PubMed1996

Decreased frequency of HLA-DRB1 13 alleles in Frenchwomen with HPV-positive carcinoma of the cervix.

Specific types of human papillomaviruses (HPV) are associated with most cases of pre-invasive and invasive neoplasia of the uterine cervix. HLA phenotype influences susceptibility and resistance to viral infections and may therefore influence the course of HPV-associated tumors. Some data suggest that specific HLA class-II alleles may be associated with protection from or susceptibility to papillomavirus-associated lesions, but these results are still controversial. Using molecular probes, we looked for associations between specific DQA1, DQB1, DRB1 HLA class-II alleles, HPV types and cervical cancer. The analysis was performed on a population of 126 patients with invasive cervical cancer. For HLA typing, 165 healthy individuals were taken as controls. The DRB1 1301/02 allele frequency significantly decreased in patients (11%) as compared to controls (29%). This difference in frequency was dependent on the HPV-positive status of tumors and was no longer significant in the group of HPV-negative lesions. The same trends were observed with the DRB1 1301/02-DQA1 0103-DQB1 0603 haplotype frequency. An increase in the frequency of the DRB1 1401/07 and DRB1 03 alleles was observed in patients under 40. Contrary to what has been reported in the literature, no increase in the DRB1 15 allele frequency was observed in our series and only a slight increase in the DQB1 03 frequency was found in patients (70%) compared to controls (58%). In our study, no positive correlations between cervical cancer in Frenchwomen and specific HLA DR-DQ haplotypes has been found. In contrast, a negative correlation between DRB1 1301/ 02 alleles and HPV-positive tumors has been observed. This may suggest a protective effect of DR13 against HPV-associated lesions of the cervix.

Adult↗
PubMed1996

Infiltrating lobular carcinoma of the breast. Clinicopathologic analysis of 975 cases with reference to data on conservative therapy and metastatic patterns.

BACKGROUND: The clinicopathologic features of infiltrating lobular carcinoma (ILC), which represents 5% to 15% of all breast cancers, are still controversial. In particular, the high frequency of multicentric lesions has led to questioning of the effectiveness of conservative treatment for this type of cancer. By studying a large number of cases, we aimed to compare the clinicopathological features of ILC with those of nonlobular infiltrating carcinoma (NLIC) and to assess the advisability of conservative therapy in the management of ILC. METHODS: The population analyzed included 726 cases of ILC, 249 cases of mixed ILC/invasive ductal carcinoma (ILC/IDC), and 10,061 cases of NLIC. The age of patients, TNM status, estrogen- and progesterone-receptor status (ER, PR), and histologic grades of the 3 groups were compared. The follow-up was carried out on a subgroup of 5846 cases. RESULTS: At diagnosis, ILC tumors were found to be larger on average and were detected in patients older than those with NLIC, but the degree of lymph node involvement was lower in patients with ILC than in NLIC. In ILC, tumors are more frequently grade I and ER-positive than in NLIC. Multicentric lesions were not significantly more frequent in ILC than in NLIC. The overall survival, locoregional control, disease free interval, and metastatic spread rates were not different among the three groups neither by univariate nor multivariate analysis, but the pattern of metastatic dissemination was different. In 480 cases of ILC considered for conservation therapy, the local recurrence and overall survival rates were similar to those observed for IDC. CONCLUSIONS: Our analysis specifies the clinicopathological features of ILC and confirms that conservation therapy may be an appropriate treatment for this type of cancer.

Breast Neoplasms↗
PubMed1996

[Precancerous and cancerous involvement of the uterine cervix. Results of a survey conducted by the "Genital Cancers" group of Ile-de-France, May 1990-May 1992, based on 8,805 biopsies].

Results of a study conducted by the "cervix cancer group" of PETRI, in Ile-de-France, from May 1990 to May 1992, and based on 8,805 biopsy specimens. In the absence of Cancer Registry in the Ile de France, no reliable data on invasive and preinvasive neoplasia of the cervix are available concerning this area. The aim of this survey, performed between May 15th, 1990 and May 15th, 1992 in 62 laboratories of pathology under the aegis of the Petri Association (Prévention et épidémiologie des tumeurs en Ile-de-France), was to obtain a better knowledge of this pathology, in which one of the major risk factors is the infection of the cervical epithelium by specific types of human papillomavirus. Over the course of these two years, 8,805 biopsy specimens, taken from neoplastic lesions of the cervix, were analyzed. Intra epithelial neoplasia represented more than 90% of the registered lesions. The average age at the time of the diagnosis was 32.4 years for the cases of condyloma, 32.7 years for CIN I, 33.8 years for CIN II, 36.3 years for CIN III, 45.7 years for micro-infiltrative carcinoma and 50.8 years for infiltrative squamous cell carcinoma. The breakdown of the different histological types of lesions is presented for three characteristic age groups (20-25, 30-35, and 60-70 years old). Differences observed in the eight departments belonging to the Ile-de-France are discussed.

Adult↗
PubMed1996

Frequent association of human papillomavirus 16 and 18 DNA with anal squamous cell and basaloid carcinoma.

Human papillomaviruses (HPVs) play a major role in the development of genital neoplasia. Their role in anal carcinogenesis is less clear, and the rate of HPV genome detected in invasive anal carcinoma varies considerably in the different reports. Moreover, the relationship of HPV to basaloid carcinoma, claimed to represent a histologic type different from the common squamous cell carcinoma, is still controversial. By use of both polymerase chain reaction and Southern blot hybridization on DNA extracted from frozen tissue specimens, we looked for HPV sequences in 12 cases of squamous cell carcinoma, in 9 cases of basaloid invasive carcinoma, in 1 case of carcinoma in situ, and in 1 case of Paget's disease of the anal canal. We have looked for correlations between virologic data and histologic types of tumors, and analyzed the clinical characteristics of HPV-positive and HPV-negative lesions. In our series, 20 (74%) of 27 cases of invasive anal carcinoma were positive for HPV DNA by Southern blot hybridization and/or polymerase chain reaction. HPV 16 DNA was found in 17 cases, HPV 18 in 2 cases, and in 1 case, the type of the HPV sequences detected remained undetermined (HPV X). Histovirologic correlations showed that 12 of 18 squamous cell carcinomas were associated with HPV 16 and that 8 of 9 cases of basaloid carcinoma were HPV positive; 5 case corresponded to HPV 16, 2 cases to HPV 18, and 1 case to HPV X. The carcinoma in situ case and the Paget's disease case were negative. An analysis of these data within the framework of the literature indicates that approximately 75% of cases of invasive anal carcinoma can actually be considered associated with HPV sequences. Basaloid carcinoma is also frequently associated with HPV genomes and is more likely to represent a histologic variant of squamous cell carcinoma than a separate entity. No clinical characteristics related to the HPV status of the tumors were observed in our series. Epidemiologic data on cervical, anal, and vulvar neoplasia are compared and their relation to the oncogenic properties of HPV in these different tissues are discussed.

Adult↗
PubMed1995

[Metastatic process].

The metastatic dissemination is one characteristic property of malignant tumors. It represents a crucial step in the progression of the disease. Multiple cellular and molecular mechanisms are involved in the dissemination of cancer cells and their proliferation at secondary sites. The metastatic process requires the transient or permanent acquisition of invasive properties mediated in part by diverse families of proteases. Numerous growth factors control the autocrine or paracrine growth of the tumor. These factors can also act as motogens and may contribute to the maintainance of the loss of the differentiated state of tumors. Angiogenesis of newly formed primary tumors is required for further growth and dissemination. Malignant cells modulate their adhesive status throughout the different steps of dissociation from the primary tumor and their intravasation and extravasation from lymph and blood vessels. Proteases, adhesion molecules, growth factors, angiogens and their cognate receptors may constitute markers to assign a metastatic phenotype and could serve as targets for the management of patients.

Animals↗
PubMed1995

A recurrent human papillomavirus integration site at chromosome region 12q14-q15 in SW756 and SK-v cell lines derived from genital tumors.

The SW756 cell line, derived from an invasive cancer of the uterine cervix, harbours integrated human papillomavirus (HPV) 18 DNA sequences which have been located in chromosome band 12q13. By in situ hybridization experiments with tritiated and digoxigenin-labelled HPV18 probes on R-banded chromosomes, we now localize the integrated viral sequences in 12q14-q15. Interestingly, we have previously localized integrated HPV16 sequences in the same chromosomal region in SK-v cells, derived from a pre-invasive vulvar neoplasia. The chromosomal region 12q14-q15 could thus correspond to a preferential site for the integration of HPV DNA in genital tumors.

Cell Line↗
PubMed1994

Analysis of interleukin 6 gene expression in cervical neoplasia using a quantitative polymerase chain reaction assay: evidence for enhanced interleukin 6 gene expression in invasive carcinoma.

Interleukin 6 (IL-6) is a multifunctional cytokine which has recently been shown to act in vitro as a growth factor for cervical carcinoma cell lines. This prompted us to measure IL-6 gene expression using a new quantitative polymerase chain reaction assay in 13 invasive cervical cancers, 5 cases of cervical intraepithelial neoplasia, and 2 normal cervix. A significant increase in the expression of the IL-6 gene in invasive cervical carcinoma as compared to cervical intraepithelial neoplasia and normal cervix was demonstrated (P < 0.05). Unlike IL-6, the expression of other cytokine genes such as gamma-interferon was not correlated with any particular cervical histological lesion. Immunohistochemical analysis identified IL-6 protein only on stroma cells which, based on morphological criteria, most likely belong to the macrophage lineage. This was reinforced by the correlation observed between IL-6 gene expression and macrophage tumor infiltration (P < 0.007). No IL-6 immunostaining of cervical tumor cells was shown. Therefore this study confirms, in vivo, that IL-6 may play a role in the pathogenesis of carcinoma of the uterine cervix since its increased expression is associated with advanced neoplastic cervical lesions. In contrast to in vitro studies, the stromal origin of IL-6 suggests that this cytokine may modulate tumor cell proliferation by a paracrine rather than an autocrine mechanism.

Base Sequence↗
PubMed1994

Mammographically-detected ductal in situ carcinoma of the breast analyzed with a new classification. A study of 127 cases: correlation with estrogen and progesterone receptors, p53 and c-erbB-2 proteins, and proliferative activity.

The new histologic classification proposed by Holland et al was applied to 127 cases of mammographically-detected ductal carcinoma in situ (DCIS). The relationship between histologic types and tumor cell expression of estrogen and progesterone receptors, p53 protein, c-erbB-2 oncoprotein, and proliferative activity markers was evaluated. There were 38 (30%) well differentiated, 39 (31%) intermediately differentiated and 50 (39%) poorly differentiated DCIS. Immunohistochemistry showed that 81% of the tumors were estrogen-receptor positive and 73% progesterone receptor positive. p53 protein and c-erbB-2 oncoprotein expression was identified in 40% and 57% of the cases, respectively. Growth-fraction determination with the Ki-67 antibody showed that 52% of the tumors had high proliferative activity. A highly significant association was found between the histologic types of DCIS and p53 protein, c-erB-b2 oncoprotein, and proliferative activity marker expression: these biological markers were more frequently overexpressed in less differentiated DCIS. No significant relationship with estrogen or progesterone receptor expression was noted. A strong relationship with the amount of tumor necrosis was also found. The clinical significance of these results should, however, be determined by long-term follow-up studies of patients with DCIS.

Adult↗
PubMed1992

Nucleoside diphosphate kinase/NM23 expression in breast cancer: lack of correlation with lymph-node metastasis.

The product of the nm23-H1 gene, reported to be a metastatic suppressor gene, was recently identified as the nucleoside diphosphate (NDP) kinase A, and was found to be overexpressed in several types of malignant tumors as compared with normal tissues. In order to determine whether NDP-kinase expression serves as a marker for metastatic potential and whether hyperproliferation of neoplastic cells would correlate with expression, we analyzed NDP-kinase levels and activity by immunohistochemical staining and by an enzymatic assay in 13 benign and 98 malignant breast-tissue specimens. Our results confirm that NDP-kinase expression increases in malignant cells of breast carcinomas, but cannot be considered as a biological marker of metastatic dissemination. No correlation was found between NDP-kinase activity and S phase, taken as an index of cell proliferation. Moreover, no correlation was observed between NDP-kinase activity and tumor size, histoprognostic index, estrogen receptors or progesterone receptors. The mechanism of over-expression of NDP in malignant cells and its role in tumor progression remain to be determined.

Breast Neoplasms↗
PubMed1992

[Ultrastructural immunocytochemical localization of diphosphate kinase/Nm23 in human cancer cells].

Nucleoside diphosphate (NDP) kinase/Nm23 is highly expressed in certain malignant tissues, as compared with the rate found in normal or hyperplastic tissues. The potential role of this overexpression in tumor progression and the mechanisms involved in it remain to be determined. We studied the ultrastructural localisation of the NDP kinase, and in particular looked for an association of this enzyme with the microtubules or cytoplasmic membrane. Using immunocytochemical methods with an antiserum raised against NDP kinase A, we analysed tissue sections of breast carcinomas and cells in culture derived from a cervical cancer. In malignant cells, a strong labeling of the cytoplasm, related to ribosomes, was observed. No labeling of microtubules, or other intracytoplasmic components was found. No labeling of the nucleus was noted. In contrast, a strong labeling of the cytoplasmic membrane of most malignant cells was observed. In the cytoplasm of non-malignant stromal cells, a slight labeling of ribosomes was observed. These results must be taken into account with regard to the different existing hypotheses relative to the role of the NDP kinase in tumor progression, and in particular relative to its activation function on the GTP-binding proteins involved in membrane signal transduction.

Breast Neoplasms↗
PubMed1992

[Ewing's sarcoma of bone in adults: an anatomic-clinical study of 30 cases].

The records of 30 adult patients with Ewing's sarcoma (ES) of bone treated between 1980 and 1990 at the Institut Curie were studied retrospectively; the diagnosis was reevaluated by histological and immunohistochemical analysis, using HNK and anti-neuron specific enolase (NSE) antibodies. The immunohistological analysis disclosed a significant staining of neoplastic cells in only few of our cases and is therefore of limited interest in the diagnosis of ES. Three groups of patients have been considered according to their clinical presentation: axial, peripheric and initial metastatic disease. The global prognosis is poor: the survival rate is 70% after a follow-up period of one year, and 23% after three years. The evolution was severe for patients with pelvic localization and/or initial metastatic disease. In contrast, five of six patients who are currently free of disease after a mean follow-up period of 42 months presented initial peripheric lesion. Four of these six patients were treated by a combination of surgical, chemical and radiation therapies.

Adolescent↗
PubMed1992

[Soft tissue angiosarcoma in a child. Immunohistochemical and ultrastructural features].

This observation reports the case of a soft tissue tumor occurring in a 11 years-old boy. On standard histologic staining, this tumor corresponded to an undifferentiated sarcoma of high grade of malignancy. Immuno-histochemical features (laminin, vimentin, UEA I and Factor VIII R-ag) and ultrastructural analysis (presence of Weibel-Palade bodies) led us to the diagnosis of angiosarcoma. This tumor is rarely reported in children and its prognosis remains unknown. Soft tissue angiosarcoma must be differentiated from Kaposi's sarcoma, epithelioid hemangioendothelioma, hemangiopericytoma and spindle cell hemangioendothelioma. This case stresses the importance of immunohistochemical and ultra-structural features in the diagnosis of poorly differentiated vascular neoplasms.

Cell Differentiation↗
PubMed1991

Overexpression of nucleoside diphosphate kinase (Nm23) in solid tumours.

The product of the nm23-H1 gene, reported to be related to the metastatic potential of tumour cells, was recently identified as the nucleoside diphosphate (NDP) kinase A (Gilles et al., 1991, J Biol Chem, 266, 8784-8789). An analysis of the enzyme by activity measurement and immunological techniques using polyclonal antibodies raised against the NDP kinase A purified from human erythrocytes, was performed on 39 human tissue specimens. Markedly increased activity and higher level of the protein were observed in extracts of solid tumours as compared to the corresponding normal tissues (P less than 0.01). An intense immunolabelling of tumoral cells was observed in sections of the malignant tumours and of some but not all benign neoplasia. The staining is observed in noninvasive and invasive ductal breast carcinomas with or without lymph node involvement as well as in colon and cervix carcinomas and in a case of metastatic melanoma. Therefore, NDP kinase A level is increased in neoplastic tissues but no correlation with metastatic potential could be demonstrated.

Blotting, Western↗
PubMed1991

Integration of papillomavirus DNA near myc genes in genital carcinomas and its consequences for proto-oncogene expression.

DNA sequences of specific human papillomavirus (HPV) types are found integrated in the cell genome in most invasive genital carcinomas. We have determined the chromosomal localization of integrated HPV type 16 (HPV-16) or HPV-18 genomes in genital cancers by in situ hybridization experiments. In three cancers, HPV sequences were localized in chromosome band 8q24.1, in which the c-myc gene is mapped, and in one cancer HPV sequences were localized in chromosome band 2p24, which contains the N-myc gene. In three of the four cases, the proto-oncogene located near integrated viral sequences was found to be structurally altered and/or overexpressed. These data indicate that HPV genomes are preferentially integrated near myc genes in invasive genital cancers and support the hypothesis that integration plays a part in tumor progression via an activation of cellular oncogenes.

Blotting, Northern↗
PubMed1990

Human papillomavirus type 16 DNA is integrated into chromosome region 12q14-q15 in a cell line derived from a vulvar intraepithelial neoplasia.

The SK-v cell line, established from a precancerous lesion (a vulvar intraepithelial neoplasia), contains 10 to 20 copies of the human papillomavirus type 16 (HPV16) genome, and was previously shown to derive from a clone of cells present in the patient's lesions. By in situ hybridization the integrated HPV16 DNA sequences were localized to a single site in chromosome region 12q14-q15. The localization of viral sequences to a single nonrearranged chromosome 12 suggests that integration occurred at this site in the patient's premalignant lesions. The INT1 and GLI protooncogenes are located in this chromosomal region. No detectable modification of the structure and expression of these genes was observed by blot hybridization experiments.

Carcinoma in Situ↗