Fifty MBCs, collected from the files of the pathology sections of the Department of Biomedical Sciences and Human Oncology of the Turin University and S. Giovanni Hospital (Turin, Italy) from 1967 to 1995 were retrospectively analysed for the expression and prognostic significance of a number of biomarkers. All patients (mean age at diagnosis: 62.2 years) underwent surgery: 45 had radical or modified radical mastectomy and 5 simple mastectomy. 35 also received adjuvant post-operative radiation, hormone or chemotherapy, alone or in combination. A minimum follow-up of 3 years for surviving patients or to death was available for all the cases. Serial sections from formalin fixed, paraffin embedded tissues, were cut for histology and morphometry, DNA flow cytometry, staining of the nucleolar organizer regions (AgNORs), and immunohistochemical detection of the proliferating cell nuclear antigen (PCNA), MIB-1, sex hormone receptors, and p53, bcl-2, c-erbB-2 and c-myc proteins. All cases were invasive ductal carcinomas; 9 were G1, 29 G2 and 12 G3; 15 were pT1, 17 pT2 and 18 pT4; 14 were N0 and 21 node positive. 27 were positive for estrogen, 25 for progesterone and 18 for androgen receptors. Positive immunostaining for p53 protein was found in 27 cases, for bcl-2 in 37, for c-erbB-2 in 28 and for c-myc in 41. Median nuclear and AgNOR area were 51μm2 and 3.54μm2, respectively; median MIB-1 and PCNA scores were 24% and 21.62%, respectively. 14 cases were DNA diploid and 16 aneuploid. In univariate analysis, tumours of high histological grade (p=0.01) and stage (p=0.006), overexpressing p53 (p=0.0008), c-myc (p=0.01) and c-erbB-2 (p=0.02) protein, with high MIB-1 (p=0.0004) and PCNA (p=0.0008) scores, large nuclear (p=0.03) and AgNOR area (p=0.005) had an unfavourable prognosis. Patients receiving only surgery had a shorter survival than those who also received adjuvant therapy (p=0.003). In multivariate analysis, only p53 (X2=10.08, p=0.001, r.r.=4.95) and c-erbB-2 immunostaining (X2=12.79, p<0.001, r.r.=4.19) as well as AgNOR quantity (X2=8.5, p=0.004, r.r.=2.89) retained independent prognostic significance. Our results show that the MBC is characterized by a high rate of oncogene expression and cell proliferative activity; p53 and c-erbB-2 expression and the rapidity of tumor cell proliferation, as indicated by AgNOR quantity, are additional parameters of high prognostic significance.
Biological characterization and prognosis of male breast carcinoma.
PICH, Achille;
2002-01-01
Abstract
Fifty MBCs, collected from the files of the pathology sections of the Department of Biomedical Sciences and Human Oncology of the Turin University and S. Giovanni Hospital (Turin, Italy) from 1967 to 1995 were retrospectively analysed for the expression and prognostic significance of a number of biomarkers. All patients (mean age at diagnosis: 62.2 years) underwent surgery: 45 had radical or modified radical mastectomy and 5 simple mastectomy. 35 also received adjuvant post-operative radiation, hormone or chemotherapy, alone or in combination. A minimum follow-up of 3 years for surviving patients or to death was available for all the cases. Serial sections from formalin fixed, paraffin embedded tissues, were cut for histology and morphometry, DNA flow cytometry, staining of the nucleolar organizer regions (AgNORs), and immunohistochemical detection of the proliferating cell nuclear antigen (PCNA), MIB-1, sex hormone receptors, and p53, bcl-2, c-erbB-2 and c-myc proteins. All cases were invasive ductal carcinomas; 9 were G1, 29 G2 and 12 G3; 15 were pT1, 17 pT2 and 18 pT4; 14 were N0 and 21 node positive. 27 were positive for estrogen, 25 for progesterone and 18 for androgen receptors. Positive immunostaining for p53 protein was found in 27 cases, for bcl-2 in 37, for c-erbB-2 in 28 and for c-myc in 41. Median nuclear and AgNOR area were 51μm2 and 3.54μm2, respectively; median MIB-1 and PCNA scores were 24% and 21.62%, respectively. 14 cases were DNA diploid and 16 aneuploid. In univariate analysis, tumours of high histological grade (p=0.01) and stage (p=0.006), overexpressing p53 (p=0.0008), c-myc (p=0.01) and c-erbB-2 (p=0.02) protein, with high MIB-1 (p=0.0004) and PCNA (p=0.0008) scores, large nuclear (p=0.03) and AgNOR area (p=0.005) had an unfavourable prognosis. Patients receiving only surgery had a shorter survival than those who also received adjuvant therapy (p=0.003). In multivariate analysis, only p53 (X2=10.08, p=0.001, r.r.=4.95) and c-erbB-2 immunostaining (X2=12.79, p<0.001, r.r.=4.19) as well as AgNOR quantity (X2=8.5, p=0.004, r.r.=2.89) retained independent prognostic significance. Our results show that the MBC is characterized by a high rate of oncogene expression and cell proliferative activity; p53 and c-erbB-2 expression and the rapidity of tumor cell proliferation, as indicated by AgNOR quantity, are additional parameters of high prognostic significance.
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