Topoisomerase IIalpha expression in ductal carcinoma in situ of the breast: a preliminary study.

Ductal carcinoma in situ (DCIS) of the breast, a precursor lesion of invasive breast cancer, is a heterogeneous disease in terms of histomorphologic features and biologic behavior. Our aim was to assess the proliferative activity, expressed as topoisomerase IIalpha (Topo IIalpha) immunoreactivity and c-erbB-2 expression in relation to morphologic features and architectural pattern of DCIS. The study included 26 DCIS, which were reclassified according to the recommendations of Consensus Conference. Topo-IIalpha and c-erbB-2 immunoreactivity were detected on paraffin sections. Topo IIalpha was consistently negative in normal ductal epithelium. Topo IIalpha-labeling index (Topo IIalpha-LI) was 0.7+/-0.6% for grade I, 4.3+/-3.9% for grade II, and 13.4+/-8.9 for grade III lesions (P<.01). For mixed nuclear grade DCIS, Topo IIalpha-LI was 6.8+/-4.8. There was no difference in Topo IIalpha-LI between different architectural patterns in low- and intermediate-grade lesions. In high nuclear grade DCIS, there was a progressive increase in Topo IIalpha-LI from solid toward cribriform and comedo-type DCIS. Positive c-erbB-2 immunoreactivity was found in 46% of DCIS, being highest in DCIS with high nuclear grade (78%) and in lesions with extensive necrosis. Topo IIalpha-LI was significantly higher in c-erbB-2-positive lesions (Topo IIalpha-LI- 12.4+/-8.5) as compared with negative lesions (Topo IIalpha-LI- 3.9+/-4.5, P<. 0001). Overexpression of c-erbB-2 and Topo IIalpha is associated with poorly differentiated lesions. Proliferative activity in individual ducts of DCIS depended primarily on the nuclear grade and was independent of architectural patterns of individual ducts in architecturally heterogeneous lesions.

Angiogenesis, p53, and c-erbB-2 immunoreactivity and clinicopathological features in male breast cancer.

BACKGROUND AND OBJECTIVES: p53, c-erbB-2, and tumor microvascular density have been shown to be potential prognostic tools in female breast cancer. Our objective was to assess the significance of these biomarkers as prognostic factors in infiltrating male breast cancer. METHODS: A retrospective study of expression of p53, c-erbB-2, and tumor microvascular density was done on a group of 26 male breast cancer patients. Biotin-streptavidin immunohistochemical study with specific anti-p53, anti-c-erbB-2, and anti-CD34 antibodies was carried out on paraffin sections of breast carcinoma. The data of expression of the biomarkers were merged with clinicopathological data such as tumor grade, T class, TNM stage, estrogen receptor status, tumor recurrence, and patient survival. RESULTS: p53 and c-erbB-2 were expressed in 46% and 39% of carcinomas, respectively. No correlation was found between positive immunoreactivity of p53, and tumor grade, size, T class, TNM stage, and survival. Nor was any relation found between tumor size, T class, TNM stage, survival, and c-erbB-2 overexpression. c-erbB-2 overexpression was significantly higher in high grade carcinomas. Estrogen receptor (ER) were positive in 21 out of 26 of tumors (81%). No trends were observed between estrogen receptor status and clinicopathological parameters or survival (data not shown). There was a positive correlation between mean microvascular density (MVD), advanced T class, and survival: higher MVD counts were found in patients with advanced tumors and in those who had tumor relapses or died of metastatic disease. CONCLUSIONS: This study suggests that tumor microvascular density may serve as a potential prognostic tool in male breast carcinoma.

Telomerase activity in ductal carcinoma in situ of the breast.

Telomerase plays an important role in maintaining the stability of the chromosomes. Activity of telomerase has been detected in proliferating and immortalized cell lines and in a number of malignant tumors including invasive breast cancer. The aim of the study was to examine telomerase activity in ductal carcinoma in situ (DCIS), which is considered to be a precursor lesion of infiltrating breast carcinoma, using a PCR-based telomerase activity protocol (TRAP). We examined 35 samples obtained from histologically confirmed breast biopsies, including 13 normal breast tissues, 11 infiltrating ductal carcinoma (IDC), nine DCIS, and two DCIS with microinvasion. Telomerase activity was demonstrated in 8/9 samples of DCIS, both samples of DCIS with microinvasion, and all but one sample of IDC. Normal breast tissue had no demonstrable telomerase activity. Our results indicate that telomerase is activated frequently in early breast carcinogenesis, although its utilization as a biomarker in DCIS is questionable.

Oncoprotein coexpression in human aberrant crypt foci and minute polypoid lesions of the large bowel.

BACKGROUND: Genetic aberrations observed in the large bowel during the neoplastic progression have a cumulative effect and are responsible for the propagation of the multistep malignant process. In the present study we evaluated the immunoreactivity of c-fos, ras, bcl-2 and p53 in aberrant crypt foci (ACF) and minute polyps of the large bowel obtained from patients with colorectal cancer. METHODS: ACF and minute polyps were collected from macroscopically normal colonic mucosa. Protein immunoreactivity was detected on parafin sections utilizing the biotin-streptavidin method on 25 hyperplastic, 10 dysplastic ACF, 5 hyperplastic and 10 dysplastic adenomas. RESULTS: 41% of the lesions displayed positive ras immunoreactivity. bcl-2 immunoreactivity was positive in six minute polyps of which five were neoplastic. fos immunoreactivity was detected in five ACF and seven minute polyps, mainly in dysplastic lesions. Two neoplastic polyps were positive for p53 immunoreactivity. Coexpression of two or more oncoproteins was found with increasing frequency in dysplastic versus hyperplastic lesions and in polypoid lesions versus ACF. CONCLUSION: Abnormal expression and coexpression in oncoproteins can be identified in the earliest stages of colorectal tumorigenesis and may contribute to the progression of selected lesions during ACF-adenoma-carcinoma sequence.

Massive gastrointestinal bleeding caused by Dieulafoy's lesion.

Dieulafoy's lesion is an anomaly, difficult to diagnose, consisting of an abnormally dilated submucosal gastric blood vessel that can cause life-threatening gastric hemorrhage. Five patients with Dieulafoy's lesion and massive gastrointestinal bleeding are described. The diagnosis was made by endoscopy in two patients and during operation in the other three. On endoscopy the source of bleeding was localized to the stomach in all patients. This information was important for the operative approach. Conservative treatment failed to prevent rebleeding, and all patients required surgery. In three patients excision of the lesion was performed, and suture only in the other two. The difficulties in diagnosis of the lesion and the surgical options are discussed.

Colchicine prevents recovery of nerve conduction at chronic demyelination.

A colchicine cuff was applied to rat sciatic nerve proximal to a demyelinating region produced by a focal injection of lysophosphatidylcholine (LPC). The colchicine cuff prevented the recovery of function normally seen within 6-8 days after LPC-induced demyelination. Colchicine blocked the delivery of sodium channels to the demyelinated region and induced their accumulation proximal to the cuff. The dual effect of colchicine in blocking both the recovery of impulse propagation through the demyelinated region and the delivery of sodium channels suggests a central role for fast axonal transport of sodium channels in the recovery of function at demyelination.