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M G Daidone

Publications and source records attributed to M G Daidone.

At least 73 records · Page 4Linked to original sources
PubMed1995

Detection of P53 expression and S-phase cell fraction in paraffin-embedded tissue by a double-labeling technique.

TP53 is a gene that normally regulates cell growth and division. Alterations to it may induce a proliferative advantage and confer an aggressive phenotype. In breast cancer, we observed a poor correlation (rs = 0.17) between P53 expression and proliferative activity evaluated as [3H]-thymidine ([3H]-dT) labeling index and an independent prognostic relevance of the two variables. We used a double-labeling technique to simultaneously evaluate the fraction of P53-positive and [3H]-dT-labeled cells to analyze the degree of association between the two markers on individual cells in order to understand their biological significance. The study was performed on a series of 44 P53-positive (P53+) breast cancers. Histological sections were immunostained for P53 with monoclonal antibody (MAb) PAb1801 and then processed for autoradiography. A weak direct relation between P53 positivity and [3H]-dT incorporation (rs = 0.4) was observed on the overall series of P53+ tumors and was maintained in subgroups defined by several biological and pathological features, except for estrogen receptor-negative tumors. The simultaneous presence of P53 expression and [3H]-dT incorporation was directly and significantly proportional to the fraction of S-phase cells of the tumor (rs = 0.7). Conversely, the fraction of cells expressing only P53 was inversely related to cell proliferation (rs = -0.66). These findings support the hypothesis that P53 has biological functions other than cell cycle regulation.

Antibodies, Monoclonal↗
PubMed1995

Biologic and clinicopathologic factors as indicators of specific relapse types in node-negative breast cancer.

PURPOSE AND METHODS: We evaluated, in 1,800 patients with node-negative tumors treated with locoregional therapy until relapse, the competitive risks for different types of metastasis by cell proliferation (3H-thymidine labeling index [3H-dT LI]), estrogen receptors (ERs), and progesterone receptors (PgRs), and by the integration of biologic and clinicopathologic information. RESULTS: Hormone receptor status and proliferative activity of the primary tumor were not indicative of contralateral failures. Hormone receptors failed to predict the 8-year incidence of locoregional recurrence, but they were significant indicators of distant metastasis and overall survival. The latter finding was confirmed even in multivariate analysis. Conversely, cell proliferation predicted both locoregional and distant metastases and survival, regardless of patient age, tumor size, and ER and PgR status. Recursive partitioning and amalgamation analysis ascribed to cell proliferation an important prognostic role for locoregional recurrence together with patient age and tumor size. CONCLUSION: Biologic markers, in particular cell proliferation, provide information for the different types of relapse and could complement the predictive role of pathologic staging.

Adult↗
PubMed1994

The Bcl-2 protein: a prognostic indicator strongly related to p53 protein in lymph node-negative breast cancer patients.

BACKGROUND: The bcl-2 gene (also known as BCL2) encodes for a mitochondrial protein thought to prevent apoptosis of normal cells. The protein has been detected by immunohistochemical procedures in hormonally regulated epithelia. PURPOSE: We analyzed the predictive relevance of Bcl-2 expression on 6-year relapse-free and overall survival in lymph node-negative breast cancers in relation to pathologic (tumor size) and biologic ([3H]thymidine-labeling index, p53 protein expression, and estrogen receptor [ER] status) features. METHODS: The expression of Bcl-2 and p53 was detected by immunohistochemistry on paraffin-embedded sections from 283 node-negative resectable breast cancers treated with local-regional therapy alone until relapse. The [3H]thymidine-labeling index was evaluated on histologic sections after incubation of fresh tumor tissue with [3H]thymidine, and ER content was determined by the dextran-coated charcoal absorption technique. RESULTS: A significantly higher fraction of Bcl-2-positive cells was observed in small, ER-positive, slowly proliferating, and p53-negative tumors than in large, ER-negative, rapidly proliferating, and p53-positive tumors. A stronger association was observed between Bcl-2 and p53 expression than between these variables and [3H]thymidine-labeling index. In univariate analysis, Bcl-2 and p53 expression, [3H]thymidine-labeling index, tumor size, and ER status were indicators for relapse-free and, with the exception of tumor size, overall survival within 6 years of surgery. In multivariate analysis, Bcl-2 failed to maintain its prognostic role for relapse-free and overall survival in the presence of p53 expression, whereas the [3H]thymidine-labeling index was still statistically significant as a predictor for both events. CONCLUSION: The predictive role of Bcl-2 expression on 6-year relapse-free and overall survival was mainly dependent on p53 expression.

Breast Neoplasms↗
PubMed1994

Expression of P-glycoprotein and in vitro or in vivo resistance to doxorubicin and cisplatin in breast and ovarian cancers.

The expression of P-glycoprotein (P-gp) was studied by immunocytohistochemistry, using the C219 monoclonal antibody, in 39 locally advanced breast cancers and 20 ovarian cancers from previously untreated patients. P-gp was expressed in 46 and 35% of breast and ovarian tumours, respectively. A significant association was observed in both tumour types between P-gp expression and in vitro resistance to doxorubicin. We also observed a higher clinical response rate to doxorubicin +/- vincristine in patients with breast cancers not expressing P-gp. Conversely, no correlation was found between P-gp expression and in vitro resistance to cisplatin or in vivo response to cisplatin +/- cyclophosphamide treatment in ovarian cancers. Our results support the relevance of P-gp expression as a specific indicator of resistance to certain drugs, such as doxorubicin and vincristine, involved in the phenomenon of multidrug resistance in breast and ovarian cancer cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

p53 as an independent prognostic marker in lymph node-negative breast cancer patients.

BACKGROUND: At present, most decisions concerning the use of adjuvant therapy in lymph node-negative breast cancer patients are made on the basis of traditional factors such as tumor size, nodal status, and histopathologic features. However, prognostic factors are being investigated that could identify high-risk groups and that could better address treatment efforts for those patients. Identification of more accurate prognostic markers, such as the expression of the mutant p53 protein encoded by the p53 (also known as TP53) tumor suppressor gene, that are reproducible, easily assessable, and independent in predicting clinical outcome would have a beneficial impact on cancer treatment decisions. PURPOSE: Our purpose was to analyze the predictive relevance of mutant p53 protein expression on 6-year relapse-free and overall survival in node-negative breast cancer patients in relation to menopausal status, tumor size, cell kinetics, and estrogen receptor status. METHODS: Expression of mutant p53 protein was detected by an immunohistochemical technique using a 1:50 dilution of PAb1801 monoclonal antibody on paraffin-embedded tumor specimens obtained from 256 axillary lymph node-negative breast cancer patients, with long-term follow-up (median, 72 months). The [3H]thymidine labeling index, a measure of cell kinetics, was evaluated on histologic sections after fresh tumor tissue was labeled with [3H]thymidine. Estrogen receptor status was determined by the dextran-coated charcoal absorption technique. Statistical comparisons were made for levels of p53 protein expression, [3H]thymidine labeling index, estrogen receptor status, tumor size, and menopausal status with respect to 6-year relapse-free survival and overall survival. RESULTS: Overexpression of the p53 protein, defined as the presence of more than 5% positive cells, was detected in 113 (44%) of 256 tumors. Odds ratios (ORs) for multiple regression analysis of 6-year relapse-free survival were significantly higher for p53 (OR = 3.24; 95% confidence limits [CL] = 2.01-5.23) and [3H]thymidine labeling index (OR = 1.92; 95% CL = 1.19-3.12), both of which appeared to be the most relevant indicators of relapse, than for tumor size (OR = 1.49; 95% CL = 0.94-2.38) and estrogen receptor status (OR = 0.91; 95% CL = 0.55-1.51). Overexpression was found to be unrelated to menopausal status. CONCLUSIONS: Immunohistochemically detected p53 overexpression is an independent marker for shortened 6-year relapse-free and overall survival in node-negative patients with resectable breast cancers. Based on these findings, p53 overexpression should be used with other established prognostic factors, such as [3H]thymidine labeling index and estrogen receptor status, to further refine the prognostic assessment of node-negative breast cancer.

Adult↗
PubMed1993

Combined analysis of ploidy and cell kinetics on fine-needle aspirates from breast tumors.

BACKGROUND: DNA ploidy and cell kinetics determined by flow-cytometric (FCM) analysis have provided relevant information on the natural history of breast cancer. These highly feasible and evaluable assays are particularly appropriate for small samples from fine-needle aspirates (FNA) to complement cytologic information for diagnosis of breast lesions. METHODS: DNA content and the percentage of cells in the cell cycle phases were evaluated on FCM DNA histograms from 281 consecutive FNA of benign and malignant breast lesions. RESULTS: FCM analysis was possible in 93% of FNA. Qualitative concordance in DNA content between FNA and surgical specimens was observed in 82% of the patients. Of the 145 aneuploid FNA, 144 (99%) were histologically diagnosed as carcinomas. The presence of only diploid clones was observed in 115 FNA: rapidly proliferating (S+G2M > 12%) diploid lesions proved to be histologically malignant in 67% of patients, and slowly proliferating diploid lesions were histologically benign in 79% of patients. False-positive results of ploidy and cell kinetics were observed in 1 and 10 patients, respectively. Of the 163 cancers evaluable for cytology and FCM, 158 were positive at cytology. The presence of aneuploid or of diploid rapidly proliferating clones in cytologically false-negative aspirates resulted in the detection of four additional cancers. CONCLUSIONS: Flow cytometric analysis of ploidy and cell kinetics on FNA could be a valuable tool complementary to cytology for breast cancer diagnosis.

Biopsy, Needle↗
PubMed1993

Quantitative immunohistochemical determination of cathepsin-D and its relation with other variables.

The expression of cathepsin D was evaluated by immunohistochemistry on histologic sections from formalin-fixed samples in a series of 436 primary breast cancers. The fraction of cathepsin D-positive tumor cells was not related to tumor size or hormone receptor status, and only weakly related to proliferative activity, evaluated as the 3H-thymidine labeling index. Conversely, a higher fraction of positive cells was observed in node-positive than in node-negative tumors (p = 0.05). A matched comparison between immunohistochemical and immunoradiometric results on individual tumors was carried out on 100 cases and showed a significant association but with a correlation coefficient of 0.46. The agreement of results from the two assays was higher in ER- than in ER+ tumors, which sometimes showed an immunostaining limited to macrophages and normal epithelial cells. In situ evaluation has the main advantage of being specifically applicable to detection in tumor cells and allows the simultaneous determination of different biologic aspects for a more complete understanding of breast cancer biology.

Breast Neoplasms↗
PubMed1993

Prognostic significance of proliferative activity and ploidy in node-negative breast cancers.

BACKGROUND: Cell kinetics and DNA ploidy have provided relevant information on the natural history of breast cancer. We assessed the prognostic role of proliferative activity and ploidy, alone and in association with tumor size, estrogen (ER) and progesterone (PgR) receptors. PATIENTS AND METHODS: In a series of 340 women with resectable node-negative breast cancers given local-regional therapy alone until relapse, proliferative activity was determined as the 3H-thymidine labeling index (3H-dT LI) and flow-cytometric S-phase cell fraction (FCM-S), as quantified by using different modeling systems. DNA ploidy, ER and PgR content were determined on frozen samples by FCM and by the dextran-coated charcoal absorption technique, respectively. RESULTS: FCM-S estimates obtained by the different models were weakly associated with one another and to the corresponding 3H-dT LIs. Four-year relapse-free survival was significantly predicted by 3H-dT LI, ploidy and tumor size but not by FCM-S. Multiple regression analysis showed that 3H-dT LI, ploidy and tumor size retained their prognostic significance and that 3H-dT LI was the most significant indicator of relapse (p = 0.009). CONCLUSIONS: The finding that 3H-dT LI and ploidy are weakly related and provide independent prognostic information could allow a more accurate identification of patients at different risk of relapse.

Breast Neoplasms↗
PubMed1993

Cell kinetics as a predictive factor in node-positive breast cancer treated with adjuvant hormone therapy.

PURPOSE: The fraction of cells that incorporate 3H-thymidine (3H-dT labeling index [3H-dT LI]) proved to be a prognostic indicator in patients with node-negative and node-positive resectable breast cancers treated with locoregional treatment alone or with adjuvant combination chemotherapy. In this study, we assessed the prognostic role of 3H-dT LI alone and in association with other pathologic and biologic variables in a series of 249 women with node-positive breast cancers treated with adjuvant endocrine therapy. PATIENTS AND METHODS: All patients were postmenopausal, had resectable estrogen receptor-positive (ER+) tumors, and had received tamoxifen for at least 1 year after radical or conservative surgery plus radiotherapy. The median follow-up duration was 48 months. RESULTS: The 4-year relapse-free survival (RFS) rates were significantly lower for patients with large tumors (> 2 cm), with more than three positive lymph nodes, with low (< 150 fmol/mg proteins) ER content, without progesterone receptors (PgRs), or with rapidly proliferating tumors. 3H-dT LI provided prognostic information independent of axillary node involvement, ER content, PgR status, and tumor size, with an estimated odds ratio (OR) higher than that of tumor size, lymph node involvement, or ER concentration. In addition, 3H-dT LI and PgR in association were able to identify patients with different risks of relapse within subsets of tumors with less or more than three positive nodes. CONCLUSION: 3H-dT LI provides prognostic information complementary to PgR, tumor size, lymph node involvement, and ER content in the prediction of RFS of postmenopausal patients with node-positive, ER + resectable tumors treated with adjuvant hormone therapy.

Aged↗
PubMed1992

Biological characterisation of primary and metachronous lesions in breast cancer patients.

Proliferative activity, evaluated as [3H]thymidine labelling index ([3H]dT LI), and hormone receptors were determined on 97 primary breast cancers and on metachronous lesions from the same patient. Overall, the [3H]dT LI of metachronous lesions was significantly higher than that of the primary tumour (P = 0.003). Hormone receptor profiles of the two lesions were similar in about 75% of the cases; disagreements were mainly due to a disappearance of hormone receptors in metachronous lesions. In contralateral tumours, [3H]dT LI and hormone receptors were unrelated to those of the relative primary lesion. In this series of relapsing patients, [3H]dT LI was unrelated to hormone receptor status in the primary tumour, but it was higher in the metachronous lesions from patients with hormone receptor-negative primary tumours. For patients given no systemic therapy between surgery and relapse, the time to develop local-regional recurrences or contralateral tumours was inversely related to the [3H]dT LI of the metachronous lesions.

Breast Neoplasms↗
PubMed1992

Potentials of cell kinetics in the management of patients with ovarian cancers.

The relevance of 3H-thymidine labeling index (3H-dt LI) on clinical outcome was evaluated on 85 patients with advanced ovarian cancers treated with carboplatin or cisplatin alone (39 cases) or cisplatin in association with doxorubicin and/or cyclophosphamide (46 cases). 3H-dT LI of the primary tumour was significantly related to the 3-year probability of survival in patients treated by monochemotherapy (low LI, 63%; high LI, 21%; P = 0.013) but not in those treated with polychemotherapy. Analysis of the relation between cell kinetics and clinical outcome as a function of treatment showed that in patients with rapidly proliferating tumours the 3-year survival was significantly higher following polychemotherapy than monochemotherapy (51 vs. 21%; P = 0.04). In patients with slowly proliferating tumours no significant difference in survival was observed following the two types of treatment for the overall series, whereas in patients not achieving a complete response survival was significantly higher following monochemotherapy than polychemotherapy (61 vs. 9%; P = 0.008).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Adjuvant CMF for node-negative and estrogen receptor-negative breast cancer patients.

From December 1980 to September 1985, a total of 90 eligible patients with stage T1-3a, node-negative, and estrogen receptor-negative (less than or equal to 10 fmol/mg of cytosol protein) tumors were entered into a randomized study to assess the effectiveness of adjuvant intravenous (IV) cyclophosphamide, methotrexate, and fluorouracil (CMF) in a subset of patients at high risk of early disease relapse. High values of [3H]thymidine labeling index were documented in two thirds of 62 assessed specimens from the patient population, and one half of the patients had histologically undifferentiated tumors. Patients were allocated to either local-regional modality alone (control group, 45 women) or to CMF (45 patients) after surgery. A full dose of CMF (600 mg/m2 each of cyclophosphamide and fluorouracil, and 40 mg/m2 of methotrexate) was administered IV on day 1, and then repeated every 3 weeks for a total of 12 treatments. After a median follow-up of 80 months, the 7-year results confirmed the superiority of adjuvant CMF compared to local-regional modality alone (relapse-free survival 85% vs 42%, P = .0001; total survival 86% vs 58%, P = .006). A benefit from adjuvant CMF was observed in all subgroups, and the rates of both local-regional and distant failure were decreased. Treatment was fairly well tolerated and devoid of life-threatening toxicity. Present results confirm our previous observation concerning the dismal prognosis of node-negative and estrogen receptor-negative breast cancer patients as well as the beneficial effect of adjuvant chemotherapy in this selected subset.

Adult↗
PubMed1991

Laminin receptors, collagenase IV and prognosis in node-negative breast cancers.

In 187 node-negative breast cancers, the expression of laminin receptors and collagenase IV was directly related in 52% of cases, independently of pathological (tumor size and histology) and biological (estrogen receptors and proliferative activity) features. Moreover, the presence of laminin receptors and collagenase IV did not appear to influence tumor proliferative activity, evaluated as 3H-thymidine labelling index. In this case series, relapse-free survival and overall survival at 6 years were significantly affected by tumor size, hormone receptor status and proliferative activity. Conversely, high levels of laminin receptors and collagenase IV failed to influence relapse-free or overall survival, whereas they were strong indicators of local-regional diffusion of the disease.

Biomarkers, Tumor↗
PubMed1991

Changes in cell kinetics induced by primary chemotherapy in breast cancer.

Changes in the 3H-thymidine labelling index (3H-TdR LI) of primary tumor induced by cytoreductive chemotherapy were evaluated in 26 patients with locally advanced breast cancer subjected to mastectomy after different systemic therapies. A significant reduction of 3H-TdR LI by primary chemotherapy was observed in 11 cases. Changes in cell kinetics were related to the pretreatment proliferative activity: significant increases were observed in 70% of tumors with a very low 3H-TdR LI (less than 25%) and significant decreases in 100% of tumors with a very high 3H-TdR LI (greater than 7.0%). There was no correlation between pretreatment 3H-TdR LI and the objective clinical response, which was conversely related to posttreatment cell kinetics. The 2-year progression rate was lower for patients whose residual tumors after treatment had remained (2/7) or become (1/8) slowly proliferating than for patients whose tumors had remained (5/7) or become (4/4) rapidly proliferating.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

3H-thymidine labeling index, hormone receptors, and ploidy in breast cancers from elderly patients.

Breast cancers from 476 elderly patients, 70 years and older, operated on since 1972, were analyzed for proliferative activity, hormone receptors, and DNA content. Tumor proliferative activity, expressed as 3H-thymidine labeling index (3H-TdR LI), had a median value of 3.4%, which progressively increased from 1972 to 1990. Estrogen and progesterone receptors were present respectively in 83% and 61% of the cases; the positivity for estrogen receptors slightly increased with time. Aneuploid clones were detected in 74% of the cases, and this incidence was relatively stable during the time of observation. 3H-TdR LI, hormone receptors, and ploidy were generally unrelated to the local-regional extension of the disease in these elderly patients, in agreement with observations on cancer from younger patients. However, the absence of hormone receptors and the presence of aneuploidy were markedly indicative of fast cell proliferation. As in younger patients, these biologic findings in elderly patients could be considered as a complement to clinico-pathologic features in a 'risk-factor profile system' for treatment planning.

Age Factors↗
PubMed1991

Comparing core needle to surgical biopsies in breast cancer for cell kinetic and ploidy studies.

The evaluability and reliability of proliferative activity (expressed as 3H-thymidine labeling index, 3H-TdR LI) and ploidy determinations on core needle biopsies were compared with those obtained on surgical material from the same breast cancers. The evaluability of 3H-TdR LI on core needle biopsies was markedly lower than that on surgical material (53% vs 100%), and the association between 3H-TdR LI values in the 16 cases with both evaluable determinations was poor (rs = 0.45). Conversely, determinations of ploidy on core needle biopsy and surgical material provided superimposable results, in terms of evaluability (91% vs 100%) and reliability (rs = 0.99). Further efforts are needed to improve sampling procedures for a reliable assessment of biological markers.

Biopsy↗
PubMed1991

New developments in breast cancer research.

The last few years have shown an extraordinary development of laboratory and clinical research in breast cancer. The areas which appear particularly important for possible clinical application are many and diversified. In this review we will update the present knowledge regarding four major issues: 1) biologic and molecular tests of prognostic significance in operable breast cancer patients; 2) detection of breast cancer cells in the bone marrow; 3) the endocrine aspects of breast cancer treatment; and 4) the indication of conservative treatments.

Breast Neoplasms↗