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F Spyratos

Publications and source records attributed to F Spyratos.

At least 73 records · Page 4Linked to original sources
PubMed1992

Sequential cytopunctures during preoperative chemotherapy for primary breast carcinoma. II. DNA flow cytometry changes during chemotherapy, tumor regression, and short-term follow-up.

Between May 1986 and May 1987, 35 primary noninflammatory breast carcinomas (T3N0-N1M0) were studied by means of DNA flow cytometry (FCM-DNA) before and after each of three courses of preoperative chemotherapy (doxorubicin, vincristine, cyclophosphamide, methotrexate, and 5-fluorouracil) to assess initial nuclear DNA content, initial S-phase fraction (SPF), and the impact of chemotherapy on these parameters. Correlations were sought with objective regression and short-term follow-up. Four sequential cytopunctures were performed for cytologic examination and FCM-DNA analyses. Ten tumors were diploid and 25 aneuploid. No significant changes in FCM-DNA parameters during chemotherapy were observed in diploid tumors, and no regression was seen in nine of the ten cases. Among the 25 aneuploid tumors, 10 showed changes in DNA content and/or kinetic parameters. A significant correlation was observed between objective regression and initial FCM-DNA content (P = 0.008), initial SPF (P = 0.004), and changes in FCM-DNA patterns observed during chemotherapy (P = 0.00005). During the follow-up period (range, 27 to 41 months), 13 patients had relapses. Patients with aneuploid tumors were more likely to have relapses (n = 11) than patients with diploid tumors (n = 2), and patients with high SPF were more likely to have relapses than patients with low SPF, but the differences were not significant. Similarly, changes in FCM-DNA parameters were observed more often in patients who had relapses, but, again, the difference was not significant. In 5 of the 13 patients who had relapses, FCM-DNA analyses were performed on cytopunctures of the recurrences: patterns were identical to those observed before treatment even when the primary tumor regressed or showed changes in FCM-DNA parameters during chemotherapy.

Adult↗
PubMed1992

Evaluation of breast carcinoma chemosensitivity by flow cytometric DNA analysis and computer assisted image analysis.

Flow cytometric (FCM) DNA and S-Phase (S%) analyses were compared to computerized image analysis (SAMBA 2005) in 27 breast carcinomas (T3, N0-N1, M0) treated by 3 cycles of preoperative Adriamycin, vincristine, cyclophosphamide, methotrexate, 5-fluorouracil (AVCMF) chemotherapy (CT). Twelve carcinomas had shown objective regression and 15 no regression. Samples studied were obtained by sequential fine-needle cytopunctures. Comparing DNA profiles obtained by both methods before and after the first cycle, it appears that tumors can be divided into 3 groups. In the first group (10 cases), no changes were observed after the first cycle of CT. These tumors before treatment had either single DNA peak without cells in S% and G2M or a major peak with a small S% and G2M peak. The second group (9 cases) showed some changes in DNA profiles with an increased G2M peak but no additional values; these tumors before treatment had a small S% and a G2M peak. In the third group (8 cases), before treatment, all were non-diploid with high S% and high G2M. After the first cycle, all showed obvious changes in DNA profiles with a decrease of the G0/G1 peak and an increased S% and G2M with dispersed additional values along the scale in (G2M) x 2 and (G2M) x 4 regions. When changes were compared to tumor regression in the 1st and 2nd groups, 1/10 and 3/9 cases, respectively, were evaluated as objective regression. In the third group, all had objective regression (p less than 0.001). In most cases, a good correlation was observed with both methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

[Optimal sampling for diagnostic and prognostic purposes before first-line chemotherapy of breast cancer].

Non-surgical first-line treatments of operable breast cancer raise the problem of pre-therapeutic collection of diagnostic and prognostic data. The advantages and limitations of cytopuncture and microbiopsy are discussed. The authors consider that the safest procedure is cytopuncture as part of diagnostic evaluation, completed by cutting-needle biopsy for information on tissues.

Biopsy, Needle↗
PubMed1991

Parathyroid hormone related protein (PTHrP) and breast cancer.

PTHrP, a newly characterized peptide is responsible for humoral hypercalcemia of malignancy in squamous cancers. It is also expressed by a variety of normal tissue and might have growth factor propriety. It is expressed by lactating breast and is frequently present in breast cancer. Although it is responsible for humoral hypercalcemia in an animal model of breast cancer its role in breast cancer hypercalcemia is still putative. The possibility that it might be one of the autocrine growth factors implicated in breast cancer cell proliferation has been suggested.

Animals↗
PubMed1991

[Reevaluation of indications for adjuvant hormone therapy in primary breast cancer with high metastatic risk].

This study concerns the correlation between ER and PR status, menopausal status and the effect of adjuvant hormonotherapy in high risk primary breast cancer patients. We have compared the results obtained in a randomized trial (Institut Paoli-Calmettes, Marseille) with those of a historic series (Centre René Huguenin, Saint-Cloud). The patients presented the same clinical and histological criteria and received identical therapeutic protocols (chemotherapy and/or hormonotherapy). Compared with patients receiving no adjuvant treatment, it appeared that: 1) in post-menopausal patients, a significant detrimental effect of tamoxifen was found in ER-negative patients, while in ER-positive patients hormonal treatment was well correlated with both the presence and level of steroid receptors; 2) in pre-menopausal patients, hormonal therapy (oophorectomy + tamoxifen) appeared to be mediated by a complex mechanism involving more than an ER-positive cell population. In the light of the published results, the present findings underline the importance of reevaluating the indications of hormonotherapy in terms of hormone receptors and menopausal status. They also indicate the importance of biological factors in the evaluation of response to therapy. They can identify, subsets of patients in whom a given therapeutic protocol is detrimental, even though it may be beneficial for the overall population. heterogeneity in response to therapy among patient subsets is one of the most important problems which confronts medical statisticians and clinical investigators.

Adult↗
PubMed1990

[Epidemiologic and prognostic factors of cancer of the breast].

Breast cancer is the most common of all cancers affecting women in France; its frequency increases in countries with a high standard of living. A family history and certain types of mastosis are unquestionable risk factors, although their weight has not yet been well established, but there is no absolute proof that feeding habits (notably fats and alcohol), which have been blamed by some authors, play a role in the genesis of breast cancer. Among the classical prognostic factors, which are necessary for surgical decisions, the size of the tumour, its histological grade and above all the number of axillary lymph nodes involved are the most important. However, a better knowledge of breast cancer biology has yielded factors that seem to be more promising than hormonal receptors, notably the DNA content of tumoral cells and the presence or absence of a protease, procathepsin 52 K, which reflects tumoral aggressiveness. As for the study of oncogens described elsewhere in this monograph, it will provide a better definition of high risk subjects and more precise information on the progress of the cancer.

Adenocarcinoma↗
PubMed1990

Flow cytometric analysis of DNA content and keratins by using CK7, CK8, CK18, CK19, and KL1 monoclonal antibodies in benign and malignant human breast tumors.

We have used a double-labelling flow cytometry analysis of keratin (CK) and DNA in breast cancer. Five monoclonal anti-keratin antibodies were tested: KL1 recognizing Mr 55,000-57,000 keratins, and "anti-glandular epithelia," LE41, RGE-53, and LP2K specific for CK n. 7, 8, 18, and 19 of Moll's classification, respectively. Flow cytometric (DNA-CK) analysis was performed on 10 benign and 19 malignant human breast tumors. All the benign tumors were diploid and 63% of the malignant tumors were aneuploid. This technique permits the analysis of DNA in the epithelial fraction alone. In aneuploid tumors, gating the DNA-keratin-positive population allowed accurate DNA analysis without interference due to debris background and non-epithelial cells. Moreover, double-labelling using the CK19 antibody gave a better identification of near-diploid tumors. An enhancement of keratin expression in malignant tumors was observed with CK 19 (P less than 0.001), KL1 (P less than 0.01), CK 8 (P less than 0.05), and CK18 (n.s.) compared to benign tumors. The comparison of keratin expression in aneuploid and diploid malignant tumors revealed reduced CK8, CK18, and CK19 in the former.

Antibodies, Monoclonal↗
PubMed1990

Epidermal growth factor receptors and prognosis in primary breast cancer.

A retrospective study was performed on 109 human breast tumors stored in liquid nitrogen in order to assess the prognostic value of epidermal growth factor receptor (EGF-R) (median patient follow-up 5 years). A significant inverse relationship was observed between EGF-R and both estrogen (ER) and progesterone receptors (PR). Univariate analysis showed a trend towards a shorter metastasis-free survival both in the overall population and in node-negative patients with EGF-R positive tumors. Multivariate analysis of the overall population showed that lymph-node involvement and PR status were the only significant variables in predicting metastasis-free survival. However, in patients receiving no adjuvant treatment (hormone therapy or chemotherapy). EGF was the only significant variable in the multivariate Cox analysis. No c-erbB-1 amplification was detected in these tumors.

Adult↗
PubMed1989

Cathepsin D: an independent prognostic factor for metastasis of breast cancer.

122 patients with primary breast cancer were followed-up for a median of 4.6 years after surgery. The concentration of cathepsin D in tumour cytosol was strongly related to both metastasis-free survival and disease-free survival and was independent of nine conventional prognostic indices. Cathepsin D assay may prove particularly useful in identifying women who, though without lymph node involvement at presentation, are at high risk of metastatic disease.

Adult↗
PubMed1989

Prognostic value of histologic grade nuclear components of Scarff-Bloom-Richardson (SBR). An improved score modification based on a multivariate analysis of 1262 invasive ductal breast carcinomas.

We did a multivariate analysis of 1262 patients with operable, invasive ductal breast carcinoma to assess the prognostic value of the Scarff-Bloom-Richardson (SBR) histologic grading system. Nodal metastasis and SBR were the two most important factors for metastasis-free survival (MFS), P = 10-9 and P = 10-5, respectively, for total study time. In patients who were node negative, the SBR and International Union Against Cancer (UICC) stages were the most important for MFS (P = 4 X 10-4 and P = 0.03). In order to try to improve the SBR prognostic value, we first studied the three components of the SBR separately: ductoglandular differentiation proved the least predictive and nuclear pleomorphism and mitotic index the most predictive. A rearrangement of the two nuclear scores alone produced higher risk values and better risk separation of patient subpopulations than SBR, and eliminated the SBR from the multivariate model. This rearrangement, modified SBR (MSBR), defined five new risk subgroups with statistically different risk ratios for MFS (P = 3 X 10-8). SBR grade II (55% of patients) was separated into three MSBR groups significantly different according to MFS (P = 0.008). In the patients who were node negative, MSBR replaced the SBR and was the most important factor for prediction of relapse of MFS (P less than 0.00001). The MSBR is more accurate and predictive than the standard SBR grade and is particularly useful when the nodal status of the patient is negative or unknown.

Adult↗
PubMed1989

Sequential cytopunctures during preoperative chemotherapy for primary breast carcinoma. Cytomorphologic changes, initial tumor ploidy, and tumor regression.

Thirty-five patients with large but operable breast carcinoma (T3, N0-N1, M0) received before surgery three cycles of preoperative Adriamycin (doxorubicin), vincristine, cyclophosphamide, methotrexate, 5-fluorouracil (AVCMF) chemotherapy (CT). All patients had sequential cytopunctures for both cytologic examination and flow cytometric DNA analysis (FCM): one before treatment and the three others after each cycle of CT. At cytologic examination, 20 carcinomas showed CT-induced cytomorphologic changes. These changes in malignant cells were also evaluated on histologic sections after surgery. A significant relationship was found between cytomorphologic changes in cytopunctures and in the corresponding tumor tissue. The lobular carcinomas did not reveal changes either on cytologic or on histologic study. At FCM analysis before treatment, ten carcinomas were diploid and 25 were nondiploid. When initial tumor ploidy was compared to cytomorphologic changes, none of the diploid carcinomas showed changes. An objective tumor regression was observed in 12 of 20 tumors with cytomorphologic changes and in four of 15 tumors without changes on cytologic examination. But, a significant relationship appeared only when cellular changes were evaluated on histologic analysis. When tumor regression was compared to ploidy before treatment, the rate of objective regression was significantly higher in nondiploid tumors (15/25) than in diploid tumors (one of ten). From these findings, initial tumor diploidy could be a predictor of tumor chemoresistance, whereas cytomorphologic changes during chemotherapy could be an indicator of tumor cell chemosensitivity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Cell-cycle studies by multiparametric automatic scanning of topographically preserved cells in culture.

The authors have developed a new methodology for characterizing in situ the cell cycle of human mammary epithelial cell lines. Using a SAMBA 200 cell image processor (scanning cytometry), 15 densitometric and textural parameters were computed on each Feulgen-stained nucleus. Parameters computed from the grey level cooccurrence and run-length section matrices allowed assessment of the chromatin pattern. Multiparametric analysis of data defined: 1) the relative position of each cell; 2) the relative positions of groups of cells, each group corresponding to a definite phase of the cell cycle; and 3) the function of these parameters best separating these phases. Files then were constructed for each phase: G0/G1, S, G2/ and M. Using these three files as a reference to classify cells, it was possible to ascertain the phase of the cell cycle for each cell of a population. The MDA AG human cell line synchronized by mitotic selection was used as a model to develop this method. The criteria used to assign cells to G0/G1, S, or G2 was DNA content. Classification in M phase was achieved by visual identification of mitotic cells. This method was checked on unsynchronized MDA AG and then applied to other human cell lines (MDA MB231, MCF-7, T47D C111). Comparison of results obtained by scanning cytometry and flow cytometry showed the proportion of cells assigned to G0/G1, S, and G2/M by the two methods to be similar. This new method removes some of the limitations of flow cytometry by 1) allowing visual verification of each cell analyzed; 2) lowering the number of cells required for study; 3) discriminating between G2 and M; and 4) preserving cell topography.

Breast Neoplasms↗
PubMed1989

Prognostic value of estrogen and progesterone receptors in primary infiltrating ductal breast cancer. A sequential multivariate analysis of 1262 patients.

Nine prognostic variables were evaluated for their significance in predicting the overall survival (OS), the length of disease-free survival (DFS) and the length of metastasis-free survival (MFS) of 1262 patients with primary breast cancer. The variables studied were: UICC clinical stage; menopausal status; histologic grade; number of involved nodes; anatomic tumor size; estrogen and progesterone receptors; local and adjuvant therapies. Three sequential multivariate analyses, at 2, 5 and 10 years, using the Cox proportional hazard regression model, were carried out to identify those variables most highly related to the criteria studied (overall, disease-free, metastasis-free survivals) and especially to fully evaluate the effects of hormonal receptors on prognosis and their stability over time. Our results showed that number of involved nodes and histologic grade were the most significant prognostic factors for all periods of time and whatever the criterion studied; ER had no predictive value while PR was an independent prognostic factor for metastasis-free survival at 2 years (P = 0.01) and 5 years (P = 0.02) but lost its significance at 10 years (P = 0.06). In the subgroup of 261 patients who received prolonged post-operative adjuvant chemotherapies, PR was the main prognostic factor for MFS at 2 years (P = 0.03) and the second at 5 years (P = 0.05) just after number of involved nodes. In the 1001 patients who did not receive prolonged post-operative adjuvant chemotherapies ER was significant for MFS at 5 and 10 years. The present data urge the need for a periodic redefinition of prognostic factors in primary breast cancer.

Adult↗
PubMed1989

Cytokeratin analysis of breast and leukemia tumor cell lines by flow cytometry.

Using four human tumor cell lines, MCF-7 and T47-D from breast tumors, MOLT-4 and K-562 from leukemia, flow cytometric DNA analysis of pure and mixed cell population was performed using monoclonal antibodies to cytokeratin to distinguish cytokeratin-containing carcinoma cells from leukemia cells which do not contain cytokeratins. Surprisingly, on pure or mixed K-562 cells, we found positive labeling with KL1, CK8, and CK18 antibodies (results confirmed by immunocytology). This preliminary study has allowed a DNA analysis on epithelial cells of human breast tumors.

Adenocarcinoma↗
PubMed1989

Immunocytochemical staining of progesterone receptor in paraffin sections of human breast cancers.

Monoclonal antibodies (mAB) against progesterone receptor (PR) and the peroxidase-antiperoxidase (PAP) method to visualize PR in paraffin sections from 68 human breast cancers were used. Ten mAB, which recognize human PR on frozen sections, were tested. Six could detect PR in paraffin sections, with Li 417, LET 456, and LET 126 giving the best results. LET 126 antibody was used for most further studies. The effects of fixation with picric acid-formaldehyde (PAF), buffered-formalin, or with Bouin solution were investigated; all fixation methods allowed PR immunolabeling, although PAF or buffered formalin usually gave the best results. Positive staining was seen in the nucleus of carcinoma cells. Variations in intensity and extent of immunoreactivity were observed in all sections and among different regions of the same specimen. These were probably related to the heterogeneity of the tumor cell population. Results were compared with the PR content in the respective tumor tissues, determined by steroid-binding assay, and with immunocytochemistry on frozen sections. It was shown that there were correlations between the immunocytochemical staining (positive or negative) and the steroid binding assay (80%) and between the immunocytochemical staining on paraffin sections and on frozen sections (78%). Weaker intensity and fewer number of PR-positive cells were found for paraffin-embedded tumors. Estrogen receptors were also detected on adjacent sections from the same paraffin-embedded tissues by use of monoclonal anti-ER antibodies (ERICA-kit[Abbott Laboratories, Chicago, IL]) and DNase pretreatment. In conclusion, this immunocytochemical method for detection of PR and ER on paraffin sections offers an alternative to frozen tissue. It allows histologic and immunocytochemical studies on the same sample and retrospective studies on stored tissue blocks.

Antibodies, Monoclonal↗
PubMed1987

Immunocytochemical study with monoclonal antibodies to progesterone receptor in human breast tumors.

Mouse hybridomas secreting monoclonal antibodies against rabbit uterine progesterone receptor (PR) have been prepared. Several of these immunoglobulins exhibited high affinity towards human progesterone receptor and two (LET 126 and LET 64) were selected as giving the best immunoperoxidase staining of human progesterone target organs. Using the indirect peroxidase-antiperoxidase method of Sternberger, optimal conditions for demonstrating PR involved brief fixation of frozen sections with formaldehyde-containing fixatives, among them picric acid-paraformaldehyde. This method allowed us to detect the receptor in breast carcinoma epithelial cells, T47D cell line, and uterine endometrium and myometrium. No staining was observed in intestine and muscle. Specific staining for PR was confined to the nucleus, irrespective of the concentration of progesterone in the blood of the patient. In a preliminary study of 27 human breast cancers by the immunocytochemical method, the presence or absence of nuclear staining for PR correlated well with the concentration of cytosolic progesterone receptor determined by a steroid-binding assay on tumor extracts. Differences in the intensity and distribution of staining within a section were observed, suggesting heterogeneity of the PR content of breast cancer cells. In 19 tumors, the immunocytochemical method for PR localization was also used in combination with a slightly modified Abbott ER-ICA staining for estrogen receptor to compare the distribution of both receptors within the same biopsy on adjacent frozen sections. Various combinations of estrogen receptor and PR contents that have been determined by steroid-binding assay have also been detected by the double immunocytochemical assay.

Antibodies, Monoclonal↗