Aberrant tetranectin expression in human breast carcinomas as a predictor of survival.

AIMS: Tetranectin (TN), a plasminogen kringle 4 binding protein, is thought to play a prominent role in the regulation of proteolytic processes via binding to plasminogen. The aim of this study was to evaluate the expression of TN in human breast cancer and adjacent normal breast tissue and to determine the impact of this expression on survival. METHODS: A retrospective analysis was performed on 189 patients with breast cancer, with a median follow up time of 10.6 years. The expression of TN was assessed in tumour tissue and adjacent normal breast tissue by immunohistochemistry, and the prognostic relevance of its expression in tumour cells was evaluated. RESULTS: TN was highly expressed in connective tissue fibres surrounding normal breast epithelium, but not in normal epithelial cells. High expression of TN in tumour cells was found in 131 (69%) of the tumour samples. By western blot analysis, no significant difference in the amount and molecular weight of TN was seen between tumour tissue and normal tissue. Strong TN immunoreactivity in tumour tissue was predictive of poor disease free and tumour specific overall survival. By multivariate analysis, high TN expression in cancer cells was an independent prognostic factor for disease free and tumour specific overall survival. CONCLUSIONS: Our results demonstrate differential TN expression in normal and malignant breast tissue and a prognostic impact of TN protein expression in breast carcinoma tissue. These data suggest a possible role of TN in invasiveness and the metastatic spread of human breast cancer.

Overexpression of p150, a part of the large subunit of the eukaryotic translation initiation factor 3, in colon cancer.

BACKGROUND: P150, a 150 kDa protein, was isolated from virally and oncogene-transformed mouse cell lines, partially purified and cloned. P150 is part of the large subunit of the eukaryotic translation initiation factor 3 with sequence homology to centrosomin A. A significant correlation between p150 expression and malignancy in breast, cervical and esophageal cancer have recently been demonstrated. MATERIALS AND METHODS: Here, 110 colorectal carcinomas of different grades and stages, including lymph node and liver metastases were compared to adjacent normal mucosa by immunohistochemistry of P150. Western blot analysis of selected cases confirmed the expression levels determined by immunohistochemistry. Additionally, immuno-electron and laser scanning microscopy (LSM) was performed. RESULTS: All investigated carcinomas revealed high levels of p150 protein compared to normal adjacent mucosa. The staining intensity was slightly heterogeneous, and positivity was correlated to the tumor grade with statistically significant differences of p150 expression between normal and neoplastic mucosa (p<0.0001, Kruskal-Wallis test). Western blots confirmed higher expression levels of p150 in the tumor. Immunogold labelling and LSM investigation showed high expression levels of p150 on the rough endoplasmic reticulum and polyribosomes, indicating that p150 is translationally active in these tumors. CONCLUSION: Thus, we propose that p150 plays an important role in development and growth of colorectal carcinomas. Furthermore, p150 expression might provide us with reliable information on the biological behaviour of tumors and the clinical course of the disease.

[Pathological examination of breast biopsy specimens]. / Pathologische Aufarbeitung von Mammabiopsaten.

No differences for long-term disease free survival could be found between breast conserving surgery and mastectomy. Most importantly is the fact that this therapy presents a significantly higher risk for local recurrence. The characterisation of this risk is one of the most important things to do. These findings result in a widespread change in treatment of breast cancer patients. Consequently an increase in interdisciplinary working between radiologists, surgeons and pathologists could be found. Histological examinations are necessary for diagnosis and exactly evaluation of the tumor extension. Microscopic evaluation of the resection margin is of most important interest, because there is a direct connection between local recurrence and tumor infiltration of the resection margin. We performed our investigations by the use of a standardized complete embedding method with the possibility of three-dimensional reconstruction, on a cohort of 280 patients. Additionally this method allowed the detection of all relevant findings on one hand and on the other hand an evaluation of all resection margins. Our results showed a breast conserving therapy including tumor free margins was performed in 67% of the patients. But there was a second resection necessary in 57% of the cases. An extensive tumor distribution as the detection of multifocal tumor spread was the reason for mastectomy in 33%. Our findings point out the necessarily of the histological examination in the line of the complete embedding method of the breast biopsy material in order to analyse the tumor including resection margin evaluation.