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  • 1
    ISSN: 1432-1335
    Keywords: Breast cancer ; Progesterone receptor ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immunocytochemical assay (ICA) of the progesterone receptor (PgR) was performed on 152 patients with stage I–II breast cancer. We employed the rat monoclonal antibody KD-68 and a peroxidase/antiperoxidase displaying system. The results obtained by ICA (PgRICA) were compared with those by the biochemical dextrancoated charcoal assay (PgRDCC). Comparing the two methods we found an overall agreement (accuracy) of 77.5%, a PgRICA sensitivity of 83.5% and a specificity of 73%. Both methods were significantly associated with oestrogen receptor expression, detected by DCC (P〈0.001 for PgRDCC andP=0.0014 for PgRICA). No significant association was found between PgRICA or PgRDCC and the other clinicopathological features analysed. After a median follow-up of 36 months, the overall survival probability was 91% in PgRDCC-positive versus 81.5% in PgRDCC-negative patients (log-rank test, χ2=0.91) compared to 87.5% in PgRICA-positive versus 82% in PgRICA-negative ones (log-rank test, χ2=0.93). Disease-free survival probability was 74.5% in both PgRDCC-positive and PgRDCC-negative patients (log-rank test, χ2=0.02) compared to 78% in PgRICA-positive versus 71.5% in PgRICA-negative cases (log-rank test, χ2=0.37). The present study demonstrates that ICA is a reliable method to detect PgR, correlating well with the DCC assay. Moreover, the ICA assay seems to provide clinical information complementary to the biochemical method. The definition of its prognostic value in operable breast cancer needs additional studies, particularly in node-negative patients.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-7217
    Keywords: cell kinetics ; histologic factors ; hormone receptors ; Ki-67 growth fraction ; prognosis ; proliferative rate ; thymidine labeling index (TLI)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Breast cancer tissue samples obtained from 147 Stage I and II patients were tested with the monoclonal antibody Ki-67 and avidin-biotin-peroxidase complex in frozen sections. The percentage of cells with nuclear staining ranged from 5% to 65%. The frequency of Ki-67 positivity was classified in five groups: 0% (45/147 = 31%); 5–9% (38/147 = 26%); 10–19% (15/147 = 10%); 20–39% (24/147 = 16%) and ⩾ 40% (25/147 = 17%). The mean value was 20%, median 18% with standard deviation of 14.5%. A significant positive correlation was observed between the presence of high Ki-67 nuclear staining rate with pathological tumor size (p = 0.003), histologic grading (p = 0.04), and axillary lymph node metastases (p = 0.009). An inverse significant correlation was found between Ki-67 and estrogen receptor expression (p 〈 0.001). No correlation was observed with progesterone receptor expression or menopausal status. The overall picture is of an inverse relationship between high growth fraction determined with Ki-67 antibody and tumor differentiation parameters. These correlations confirm those already reported by thymidine labeling index and flow cytometry methods. The proliferative rate determined with Ki-67 antibody may provide information regarding cell kinetics of breast carcinoma, potentially useful in identifying patients with a different clinical course in order to improve the therapeutic approach, by a rapid, practical and easily performed immunohistochemical method.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-7217
    Keywords: breast cancer ; epidermal growth factor receptor ; immunocytochemistry ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Epidermal growth factor receptor (EGFR) is a potentially useful new biological prognostic and predictive indicator in human breast cancer. Additional research on EGFR is warranted to enhance our information on: i) the method of choice for its detection and quality control issues; ii) its association with novel pathobiological markers of prognosis; iii) its prognostic value in multivariate analysis; and iv) its capability to predict response to hormone therapy and, in the future, to biological treatments using antibodies against the specific receptor or its ligands. In the present study we update previous data on EGFR status, determined immunocytochemically, by prolonging the period of observation up to 5 years and by including, in the multivariate analysis, several new biological indicators. The main results obtained are: i) EGFR is weakly associated with Ki-67 score (p=0.073) and with p53 expression (p=0.06); ii) EGFR is a significant indicator for recurrence (p〈0.01 and odds ratio of 2.82) but not for death (p=0.27 and odds ratio of 1.49); iii) the prognostic power of EGFR is enhanced when combined with the knowledge of S-phase fraction; and iv) in multivariate analysis on relapse-free survival, EGFR and S-phase fraction (likelihood ratio test=26.40; p〈0.01), c-erbB-2 protein and p53 mutant protein expression (likelihood ratio test= 5.94; p=0.05), cathepsin D (likelihood ratio test= 9.78; p〈0.01), and nodal status (likelihood ratio test= 7.32; p〈0.01) are significant and independent prognostic factors in early-stage breast carcinoma. This new information could be of help for a more rational approach in the use of EGFR as a marker in future clinical research.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-7217
    Keywords: c-erbB-2 protein ; histologic grade ; Ki-67 ; laminin receptor ; multivariate analysis ; node-negative breast cancer ; p53 ; peritumoral lymphatic vessel invasion ; prognosis ; tumor angiogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the present study we update previous results on the prognostic value of intratumoral microvessel density (IMD), determined immunocytochemically using the monoclonal antibody CD-31 and a standard streptavidin-immunoperoxidase technique, published in theJ Clin Oncol 12:454–466, 1994. This study was undertaken in those 211 node-negative breast cancer (NNBC) cases of that series of which we had pathological material available to determine all the prognostic indicators. The median period of follow-up has been extended to 78 and 80 months for relapse-free survival (RFS) and overall survival (OS), respectively, and new biological indicators (i.e. Ki-67 labeling and 67 kDa laminin receptor expression) were included in the analysis. The main results obtained are:i) a confirmation that IMD is not associated with the other biological markers studied, i.e. expression of p53 protein, c-erbB-2 protein, 67 kDa laminin receptor, and cell kinetics; IMD was weakly associated only with histological grade (p=0.053);ii) IMD remains a highly significant prognostic factor for RFS and OS (p〈0.0001 and p=0.018, respectively) in univariate analysis;iii) in multivariate analysis on RFS, IMD (likelihood ratio test (LRT)=30.16; p〈0.0001), 67 kDa laminin receptor (LRT=9.80; p=0.0017), the IMD/67 kDa laminin receptor interaction (LRT=8.62; p=0.0033), tumor size (LRT=8.56; p=0.0034), and p53 protein (LRT=4.96; p=0.025) are significant and independent prognostic indicators. For OS, only tumor size (LRT=8.34; p=0.0038), menopausal status (LRT=5.16; p=0.023), p53 protein (LRT=4.37; p=0.036), and IMD (LRT=4.05; p=0.044) retain a significant and independent prognostic value. The results of this study confirm the prognostic importance on RFS of the variables previously tested, but not of peritumoral lymphatic vessel invasion. A novel finding is that 67 kDa laminin receptor and the IMD/67 kDa laminin receptor interaction are also significant and independent variables. For OS, the results confirm that both IMD and tumor size are significant and independent variables. With prolonged follow-up the novel finding that emerges is the prognostic importance of menopausal status and p53 protein. This new information could be useful for a more accurate selection of high-risk NNBC patients who require careful follow-up and may benefit from adjuvant therapy.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-7217
    Keywords: breast cancer ; peritumoral lymphatic invasion ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In 164 breast carcinomas the presence of peritumoral lymphatic vessel invasion (PLVI) was evaluated and correlated with other known indicators of prognosis and with the clinical outcome of the patients. Overall 22% of tumors were PLVI-positive. The presence of PLVI was significantly associated with axillary node involvement (p〈0.0001) and tumor size (p=0.005), and tended toward an association with grading (p=0.065). No significant association was found between PLVI and steroid hormone receptors, DNA ploidy, or proliferative activity. Univariate analysis shows that peritumoral vessel invasion was significantly associated with a higher risk of recurrence (p=0.012) and with a trend toward shorter survival (p=0.074). Besides the presence of PLVI, prognosis was significantly worse also for patients with high proliferative aneuploid tumors and with axillary node metastases. Moreover, within the subsets of patients generally considered to have good prognosis, the presence of PLVI identified patients with a trend for higher risk such as those with PLVI-positive diploid tumors, PLVI-positive low-proliferative tumors, and PLVI-positive node-negative tumors. Adopting multivariate analysis, PLVI failed to retain prognostic importance when adjusted for node status, DNA ploidy, and proliferative activity. In conclusion, we found that the presence of PLVI has prognostic significance when singly evaluated. Multivariate analysis shows that PLVI is not an independent prognostic factor in stage I–II breast cancer.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-7217
    Keywords: breast cancer ; immunocytochemistry ; Ki-S1 antibody ; prognosis ; proliferation markers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a series of 205 node-negative breast cancers (NNBC), we determined staining by the novel antibody Ki-S1, a marker of tumor cell proliferation, in order to test its association with other prognostic variables and its prognostic significance. Ki-S1 was determined in routinely formalin-fixed paraffin-embedded tumor samples. Ki-S1 gave a nuclear staining in the majority of the carcinomas (188 of 205), with percentages of reacting nuclei ranging from 2% to 90% (median value of 7%). In 107 tumors frozen sections were available to also assess the Ki-67 antibody. Among these, 94 had a nuclear staining of cancer cells ranging from 5% to 80% (median value of 7%). In 46 tumors we also determined the MIB-1 antibody. The percentage of MIB-1 nuclear staining ranged from 1% to 50% (median value of 20%). There was no significant relationship between Ki-S1 and the other two cell kinetic markers. Ki-S1 labeling was significantly associated only with tumor size (p = 0.03). With a median follow-up of 6 years, Ki-S1 had no significant prognostic value for either relapse-free survival (RFS) or overall survival (OS)(Ki-S1 as continuous logarithmic variable; p = 0.86 and p = 0.23, respectively). For RFS the following variables had a significant prognostic value: Ki-67 (≤ 10% vs 〉 10%; p = 0.037); progesterone receptor (PgR) expression (− vs +/++; p = 0.041); tumor size (pT1 vs pT2−3; p = 0.042) and grading (GI vs GII−III; p = 0.047). For OS, tumor size (p = 0.0044), age (continuous variable; p = 0.0060), and Ki-67 (p = 0.043) were significantly prognostic. In multivariate analysis (final model), only tumor size retained a significant and independent prognostic value for RFS (p = 0.0042). For OS, both tumor size (p = 0.0029) and age (≤ 55 years vs 〉 55 years; p = 0.041) retained significance in the multivariate model. In conclusion, Ki-S1 does not seem to have prognostic relevance in this series of NNBC. Possible hypotheses to explain this observation are discussed.
    Type of Medium: Electronic Resource
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