CGH analysis of ductal carcinoma of the breast with basaloid/myoepithelial cell differentiation.

2-18% of ductal carcinoma-No Special Type (NST) are reported to express basal cell keratin 14 and such tumours may have a different metastatic pattern and prognosis. We performed immunohistochemistry for cytokeratins 19 (luminal) and 14 (basal) on 92 ductal carcinoma-NST. Those tumours showing CK14 expression were further characterized by immunohistochemistry for myoepithelial cell phenotype and analysed by comparative genomic hybridization. The 7 cases of ductal carcinoma-NST exhibiting a basal cell phenotype were all grade III tumours and showed a molecular cytogenetic profile similar to more conventional myoepithelial cell carcinomas. Therefore it appears that grade III invasive ductal carcinomas contain a subset of tumours with specific morphological and cytogenetic characteristics, and probably prognosis for the patient.

Immunophenotype, ras oncogenes and p53 onco-suppressor gene in benzo(a)pyrene induced malignant soft tissue tumours in Wistar rats.

This study was designed to identify the immunophenotypic characteristics of malignant soft tissue tumours, induced experimentally with benzo(a)pyrene (BaP), and to evaluate the immunohistochemical expression of the ras oncogene family and p53 onco-suppressor gene in these tumours, in association with prognostic factors. Seventy-five male Wistar rats were subcutaneous injected, dorsally, with a single dose of 10.08 mgr BaP. A solid, well-circumscribed tumour was formed at the injection site, in 70 of the animals, 80-100 days after the carcinogen's administration. The tumour as well as selected main organs were excised and studied after the animals' death. All the specimens were fixed in formalin 10%, embedded in paraffin and stained with H + E. The immunohistochemical avidin-biotin method was performed in the tumour sections, using the following monoclonal or polyclonal antibodies: vimentin, desmin, muscle specific actin (MSA), a-smooth muscle actin (SMA), myoglobin, smooth muscle myosin, a-1-antitrypsin, a-1-antichymotrypsin, S-100 protein, epithelial membrane antigen (EMA), K-ras, H-ras, Pan-ras and p53. The induced tumours of the animals were almost well-circumscribed, with a partly storiform cut surface. Histologically, their appearance was more conventional with high grade leiomyosarcomas; about half of them showed highly anaplastic areas, resembling other pleomorphic undifferentiated sarcomas. Pulmonary metastatic foci were detected in 37 animals. Immunohistochemically, all the tumours displayed positive expression of vimentin, MSA and SMA. Desmin was positively expressed in 40 tumours, smooth muscle myosin in 57 tumours and EMA in 12 tumours. All the tumours were negative for myoglobin, a-1-antitrypsin, a-1-antichymotrypsin and S-100 protein. In addition, five tumours showed a positive reaction for K-ras p21, 37 for H-ras p21, 41 for Pan-ras p21 and 14 for p53 protein. The overexpression of the oncoproteins H-ras p21 and Pan-ras p21 in these tumours was significantly associated with a non-advanced tumour stage (absence of metastatic focus). In conclusion, the histological as well as the immunophenotypic features of the induced tumours are more conventional with leiomyosarcomas mostly of high grade; many of them are "dedifferentiated". The identification of both ras and p53 gene products in these tumours indicates that alterations of these genes are common but not specific events, implicated in the tumourigenesis, which may become prognostic markers for this subtype of soft tissue sarcomas.

p53/MDM-2 immunohistochemical expression correlated with proliferative activity in different subtypes of human sarcomas: a ten-year follow-up study.

The aim of this study was the evaluation of p53/MDM-2 protein overexpression in different subtypes of human sarcomas, and their correlation with proliferative activity and patient outcome. We selected 40 cases of human sarcomas comprising 6 malignant fibrous histiocytomas (MFH), 1 fibrosarcoma, 1 dermatofibrosarcoma protuberans, 5 liposarcomas, 9 leiomyosarcomas, 1 rhabdomyosarcoma, 3 synovial sarcomas, 2 osteosarcomas, 1 chondrosarcoma, 4 Ewing's sarcomas, 2 Kaposi's sarcomas, 1 malignant haemangiopericytoma, 1 phylloides cystosarcoma, 1 neuroblastoma, 1 chordoma and 1 unclassified sarcoma. All the immunohistochemical markers, which had been used for the characterization of these sarcomas were re-examined. Additionally, the Streptavidin-Biotin peroxidase method was performed on paraffin sections using the monoclonal antibodies: anti-p53 antibody DO7, anti-MDM-2 antibody IF2 and anti-Ki-67 antibody MIB-1. According to our results, p53 protein nuclear expression was detected in 20% (8/40) of the tumours (1 fibrosarcoma, 2 liposarcomas, 1 leiomyosarcoma, 1 rhabdomyosarcoma, 2 Ewing's sarcomas and 1 unclassified sarcoma). MDM-2 nuclear staining was determined in 7.5% (3/40) of the cases (1 MFH and 2 liposarcomas). A high proliferative index was demonstrated in 27.5% (11/40) of the tumours (2 MFH, 4 leiomyosarcomas, 1 rhabdomyosarcoma, 1 osteosarcoma, 2 Ewing's sarcomas and 1 unclassified sarcoma). p53 overexpression was associated with high tumour grade (p < 0.05) and MIB-1 expression was correlated with reduced survival (p < 0.05), but p53 overexpression was not significantly associated with either MIB-1 score or with overall survival of the patients. In conclusion, from this limited and heterogeneous sample of cases, we suggest that the p53/MDM-2 pathway is involved in the tumourigenesis of several sarcoma subtypes, but it is unclear if the overexpression of these genes may become prognostic marker for patients affected with these highly aggressive tumours.