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  • 1
    Electronic Resource
    Electronic Resource
    Differentiation in paediatric peripheral primitive neuroectodermal tumours of bone (1998)
    Springer
    Virchows Archiv 432 (1998), S. 505-513 
    Details
    ISSN: 1432-2307
    Keywords: Key words Peripheral primitive neuroectodermal tumour ; Immunocytochemistry ; Differentiation ; Survival ; Statistical analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Differentiation was studied in 73 paediatric peripheral primitive neurorectodermal tumours (pPNETs) of bone observed during 1974 through 1992. The presence of rosettes, pseudorosettes, and/or a rosette-like arrangement of tumour cells (the morphological neural marker, MNM) occurred in 29% of these cases. NSE and N-CAM were expressed by nearly all tumours; synaptophysin was present in 30% of cases, not significantly associated with the MNM status. Neuroendocrine (NE) markers were present in 25% (chromogranin B, secretogranin II) to 40% (chromogranin A, 7B2 protein) of cases. Focal expression of cytokeratins, S100 protein and/or desmin was also noted in a minority of cases. In univariate statistical analysis, only the presence of MNM conferred a significantly higher (about twofold) risk of death than its absence. This study demonstrates the occurrence of at least one immunocytochemical N and/or NE differentiation marker in all pPNETs of bone and a focal expression of cytokeratins, S100 protein and/or desmin in a minority of cases. Synaptophysin and MNM were present each in less than 1/3 of the cases, and no association was noted between them. Statistical analyses highlighted the prognostic role of MNM per se and discourage the sole use of immunocytochemistry in the assessment of neuroectodermal differentiation for prognostic purposes in paediatric pPNETs of bone.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004280050198
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  • 2
    Electronic Resource
    Electronic Resource
    Behaviour of metastasis in relation to vascular index in patients with node-positive breast cancer treated with adjuvant tamoxifen (2000)
    Springer
    Clinical & experimental metastasis 18 (2000), S. 15-20 
    Details
    ISSN: 1573-7276
    Keywords: adjuvant therapy ; angiogenesis ; metastasis ; tamoxifen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Some experimental studies suggested that one possible oestrogen-receptor-unrelated mechanism of action of tamoxifen involves inhibition of angiogenesis. We evaluated the correlation of the degree of vascularisation of the primary tumour and we assessed it by using the panendothelial marker anti- CD31 and immunohistochemistry with microvessels count, performed at the vascular ‘hot spot’ of each single cancer, with the risk of recurrence in time. A cohort of 176 consecutive patients with node-positive invasive breast cancer treated with adjuvant tamoxifen (30 mg/daily for 3 years) and a median follow-up of 72 months was studied. Sixty-two patients developed metastasis (30 visceral, 18 skeletal and 14 in soft tissues) during the time of observation. The study of the hazard function for metastasis was performed by a generalized linear modelling approach with a binomial error according to Efron. The risk of first recurrence was strictly associated with vascular index, having the patients with the highest microvessel counts the highest risk of metastasis during all the period of observation. We did not find an interaction of vascularity with oestrogen receptor (ER) status. However, in the subgroup of patients with ER-positive tumours the hazard of metastasis was almost constant in time, while in that with ER-negative tumours it increased rapidly up to 20 months and, thereafter, decreased sharply. The results of our study are an indirect evidence that the patients with highly vascularized breast cancers may gain poor benefit of adjuvant tamoxifen and, therefore, that this antioestrogen is unlikely to retain a clinically relevant antiangiogenic activity in human breast cancer. Our data need confirmation by a prospective randomized clinical trial.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026574818241
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  • 3
    Electronic Resource
    Electronic Resource
    Lack of prognostic significance of the monoclonal antibody Ki-S1, a novel marker of proliferative activity, in node-negative breast carcinoma (1996)
    Springer
    Breast cancer research and treatment 37 (1996), S. 123-133 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF01806494
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  • 4
    Electronic Resource
    Electronic Resource
    Quantitative measurement of soluble cytokeratin fragments in tissue cytosol of 599 node negative breast cancer patients: a prognostic marker possibly associated with apoptosis (2000)
    Springer
    Breast cancer research and treatment 59 (2000), S. 211-221 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; breast cancer ; continuous variables statistical analysis ; cytokeratins ; multiple correspondence analysis ; prognosis ; tissue cytosol ; tissue polypeptide antigen (TPA)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Apoptosis is associated with caspase-mediated proteolysis of Type I (K18 and K19) cytokeratins. We previously showed a positive association between the levels of tissue polypeptide antigen (TPA), that recognizes cytokeratins K8, K18, and K19 fragments, and induced apoptosis in breast cancer cell lines. The aim of the present study was to evaluate the interrelationships between TPA, steroid receptors, and p53, and their joint prognostic role in node-negative breast cancer patients not treated with adjuvant therapies. Age and pT were also considered since they are known prognostic factors. Five hundred and ninety-nine cases with N- breast cancer were evaluated (median follow-up: 60 months). TPA was measured by an immunoradiometric assay and p53 by an immuno-chemiluminescent assay in tumor cytosol. Multiple correspondence analysis was used to study the associations among variables. Their prognostic role (univariate analysis) and their joint effect (multivariate analysis) on RFS were investigated with Cox regression models. TPA showed a direct association with ER and PgR. Higher p53 values were weakly associated to low values of ER, PgR, and TPA. Younger age was related to low and intermediate values of ER and PgR and to low p53 values, while older age was related to high values of ER. Multivariate analysis showed a significant prognostic impact for pT, age, ER, and TPA. Among the interactions considered clinically relevant, only that between ER and age was found. RFS estimated values were poorer in cases with lower than in those with higher TPA values, both in patients expected to have a poor (pT2, young age, low ER) and a better prognosis (pT1, older age, high ER). From the findings of the present study we can draw the following conclusions: The relationship of TPA with prognosis gives an additional contribution to pT, age, and steroid receptors in N- breast cancer; TPA may be considered the first marker of apoptosis measured with a fully standardized quantitative method in tumor cytosol and could be evaluated in prognostic indexes including markers related to different biological mechanisms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006318112776
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  • 5
    Electronic Resource
    Electronic Resource
    Co-determination of the angiogenic factors thymidine phosphorylase and vascular endothelial growth factor in node-negative breast cancer: prognostic implications (1997)
    Springer
    Angiogenesis 1 (1997), S. 71-83 
    Details
    ISSN: 1573-7209
    Keywords: Angiogenesis ; breast cancer ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Experimental and clinical studies have shown that human breast cancer is an angiogenesis-dependent neoplasm. In fact, several authors have demonstrated that the determination in primary tumors of the degree of vascularization (microvessel counts) as well as of some angiogenic peptides is of prognostic value. However, which are the most important mediators of angiogenesis and their relationship with other relevant biological markers needs further investigation. In the series of 260 women with node-negative breast cancer (NNBC) on which we previously assessed vascular endothelial growth factor (VEGF), we have now also determined thymidine phosphorylase (TP) protein as well as p53 protein and Cathepsin-D cytosolic levels using immunometric methods. The median concentrations of TP, p53 and Cathepsin-D were 105.4U/mg (range 1.2–843.1), 0.22 ng/mg (range 0.0–41.65) and 33.80nmol/mg (range 4.20–216.0), respectively. We found that TP concentrations were associated with Cathepsin-D and p53, but not with VEGF. VEGF (p〈0.0001) and p53 (p = 0.03 and p = 0.012, respectively) were found to be statistically significant prognostic variables for both relapse-free survival (RFS) and overall survival in univariate analysis. Conversely, TP and Cathepsin-D levels did not correlate with prognosis. In multivariate analysis for RFS, VEGF levels (p〈0.0001), TP levels (p = 0.050) and their first-order interaction terms (p = 0.027) were statistically significant prognostic indicators. Cathepsin-D and p53 protein levels did not retain significance in the model inclusive of all the above variables. The predictive capability of the complete model was satisfactory (Harrell c statistic = 0.72). Moreover, these results suggest a possible potentiation of the capability of predicting the likelihood of recurrence by the co-determination of TP and VEGF. The probability of recurrence was particularly high in the patients with primary tumors characterized by elevated levels of both angiogenic factors. This is the first study showing in vivo that two different angiogenic peptides concur in the progression of human breast cancer. The biology and possible therapeutic implications of this observation are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018305132489
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  • 6
    Electronic Resource
    Electronic Resource
    Peritumoral lymphatic vessel invasion compared with DNA ploidy, proliferative activity, and other pathologic features as prognostic indicators in operable breast cancer (1991)
    Springer
    Breast cancer research and treatment 20 (1991), S. 195-204 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF01834625
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  • 7
    Electronic Resource
    Electronic Resource
    A multiparametric study on the prognostic value of epidermal growth factor receptor in operable breast carcinoma (1994)
    Springer
    Breast cancer research and treatment 29 (1994), S. 59-71 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00666182
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  • 8
    Electronic Resource
    Electronic Resource
    Prognostic value of intratumoral microvessel density, a measure of tumor angiogenesis, in node-negative breast carcinoma — results of a multiparametric study (1995)
    Springer
    Breast cancer research and treatment 36 (1995), S. 205-217 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00666041
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  • 9
    Electronic Resource
    Electronic Resource
    Fenretinide (4-HPR) in chemoprevention of oral leukoplakia (1993)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 53 (1993), S. 255-261 
    Details
    ISSN: 0730-2312
    Keywords: chemoprevention ; fenretinide ; oral leukoplakias ; clinical trials ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: A controlled clinical trial has been underway at the Istituto Nazionale Tumori (INT) of Milan since 1988. The goal of the trial is to evaluate the effectiveness of fenretinide (4-HPR) in preventing relapses, new localizations, and carcinomas in patients with benign postoperative diagnoses who have been surgically treated for oral leukoplakias. This paper presents the design and the preliminary results of this study. To date, 137 patients have been randomized, following surgical excision of oral leukoplakia, to receive either 200 mg 4-HPR daily for 52 weeks or no intervention. Twenty local relapses or new localizations have occurred so far in the control group and 9 in the 4-HPR group. Seven patients have interrupted the intervention because of toxicity. No impaired dark adaptation has been observed. We conclude that 4-HPR is well-tolerated and appears to be effective in preventing relapses and new localizations during the treatment period.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240531038
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  • 10
    Electronic Resource
    Electronic Resource
    Controlled clinical trials with fenretinide in breast cancer, basal cell carcinoma and oral leukoplakia (1995)
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 59 (1995), S. 11-17 
    Details
    ISSN: 0730-2312
    Keywords: 4-HPR ; chemoprevention ; fenretinide ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: We are conducting three randomized studies (breast cancer, basal cell carcinoma, oral leukoplakia) and report our methodological approach and accrual here.The aim of the breast cancer study is prevention of a contralateral primary lesion in women already treated for breast cancer; the aim of the basal cell carcinoma study is prevention of recurrences or new occurrence after surgical resection; and the aim of the oral leukoplakia study is prevention of recurrences and new occurrence after CO2 laser resection. The studies were planned according to a randomized design with an intervention arm vs a no-treatment arm. Patients in the intervention group receive 4-HPR at a dose of 200 mg po. The duration of treatment is five years in the breast cancer study, and one year in the basal cell carcinoma and oral leukoplakia studies. The breast cancer study started in March 1987, closing accrual on July 31, 1993. A total of 2,972 patients entered the study; 2,849 were evaluable (1,422 in the 4-HPR group and 1,427 in the control group). Of 2,849 evaluable patients, 867 completed the first five years, 1,142 are still ongoing, and 840 patients have interrupted the study for various reasons. Follow-up is ongoing. The basal cell carcinoma study started in January 1990. As of January 1994, a total of 786 patients had entered the study; 760 were evaluable (363 in the 4-HPR group and 367 in the control group). Of 760 patients in the study, 568 completed the first year, 62 are ongoing and 130 discontinued for various reasons. The study is ongoing. The oral leukoplakia study started in September 1988, closing accrual on February 1, 1994. A total of 174 patients entered the study; 170 were evaluable (84 in the 4-HPR group and 86 in the control group). The preliminary data of this study have been published. Updated results as of June 1994 were 11 recurrences and three new occurrences in the 4-HPR group; the control group also had 11 recurrences, as well as 12 new occurrences. Follow-up is ongoing.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jcb.240590803
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