The predictive value of serum soluble E-cadherin levels in breast cancer patients undergoing preoperative systemic chemotherapy.

OBJECTIVES: To date, no reliable markers are available to predict response to or to assess prognosis after preoperative systemic chemotherapy (PST) in patients with locally advanced breast cancer. Previous studies demonstrated that elevated levels of soluble E-cadherin (sE-cadherin), a product of proteolytic cleavage of cell surface E-cadherin, are associated with higher risk for metastatic disease and poor prognosis in various tumor types. We, therefore, hypothesized that serum sE-cadherin levels measured before PST may correlate with pathological response. DESIGN AND METHODS: In a retrospective analysis, sE-cadherin levels were measured in sera of 108 female patients with histologically proven breast cancer before initiation of PST by using a commercially available quantitative sandwich enzyme immunoassay technique. Patients received a median number of 4 (range 3-6) cycles of anthracyline-based chemotherapy. The median patient age was 51.5 (range 21-71) years. Tumor size was measured clinically and translated into the tumor-node-metastasis (TNM)-system before the start of chemotherapy. Histopathological response in surgically removed specimens was evaluated using a modified Sinn regression score. In univariate analyses the correlations between levels of sE-cadherin and pathological response to PST were calculated. RESULTS: The histopathological regression scores correlated significantly with tumor grading (p=0.045), clinical lymph node status before PST (p=0.031) and sE-cadherin levels (p=0.039). No correlation was seen between histopathological regression scores and hormone receptor and menopausal status as well as Her2-neu status. CONCLUSION: sE-cadherin may be a marker predicting response to PST for patients with breast cancer. Our findings warrant further evaluation of sE-cadherin in a prospective trial.

[Sophrology: a different tool for infertile couples]. / La sophrologie caycédienne: une autre approche du couple infertile.

Because of the high degree of complexity of assisted reproduction techniques (ART), the human and conscious dimensions of infertility problems are often neglected. Different strategies may help infertile couples coping with infertility and related treatments; among these, Caycedian sophrology relies on the cognitive, emotional, and somatic aspects of consciousness. In the present article, the authors report on their experience with sophrologic support for infertile patients by a midwife qualified in caycedian sophrology. Overall, since 1988, 310 couples have benefied from this kind of support, with an average of 10 sophrologic trainings per patient. Whereas some couples consider sophrology as a short time training to better cope with any particular aspect of their infertility treatment, others want to undertake more profound work on their body scheme. The authors wish to call the attention of ART professionals to this kind of medical support for infertile couples, and also to the particular role of midwives with sophrologic competence in an ART center.

Activation of the MAP kinase pathway induces chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) expression in human breast cancer cell lines.

Growth factors are essential for cellular growth and differentiation in both normal and malignant human breast epithelial cells. In the present study we investigated the effect of epidermal growth factor (EGF), transforming growth factor alpha (TGFalpha) and phorbol myristate acetate (PMA) on chicken ovalbumin upstream promoter-transcription factor (COUP-TF) expression in human breast cancer cells. The orphan receptors COUP-TFI and COUP-TFII are members of the nuclear receptor superfamily. The high degree of evolutionary conservation of these proteins strongly argues for an important biological function. COUP-TF expression was highest in SK-BR3 cells (approximately 130 amol/ micro g total RNA), while the lowest COUP-TF expression was observed in MCF-7 cells (3.5 amol/ micro g total RNA). While treatment of EGF, TGFalpha and PMA induced expression of COUP-TFII, COUP-TFI did not respond to these agents. Oncostatin M (OSM) is known to exert an antiproliferative effect in breast cancer cells. Treatment of MCF-7 cells with OSM resulted in an approximately 90% reduction of COUP-TFII mRNA expression. In SK-BR3 cells, treatment with the MEK inhibitor UO126 resulted in a profound suppression of endogenous COUP-TFII expression. Furthermore, cotreatment with UO126 prevented induction of COUP-TFII expression by EGF in MCF-7 cells. In conclusion, our data provide evidence, for the first time, that mitogenic substances which activate the MAP kinase pathway, can induce COUP-TFII expression. Our results strongly suggest that an active MAP kinase pathway is essential for COUP-TFII expression in human breast cancer cells.

Prognostic factors in surgically treated stage ib-iib cervical carcinomas with special emphasis on the importance of tumor volume.

OBJECTIVE: The aim of the study was to analyze the importance of tumor volume as a prognostic factor for overall survival (OS) in surgically treated stage Ib-IIb cervical carcinoma. METHODS: One hundred thirteen of one hundred sixty-five patients with histopathological stage Ib-IIb cervical carcinoma (44 Ib1, 24 Ib2, 10 IIa, 35 IIb) treated by radical abdominal hysterectomy between 1989 and 1999, for whom tumor volume could be assessed, were included in this study. Of the 113 patients, 90 (79.6%) received postoperative radiotherapy. Measurement of tumor volume was performed on giant histological sections using a semiautomatic image analyzer. The prognostic significance of tumor volume was analyzed and compared with that of various clinicopathological parameters using uni- and multivariate statistics. RESULTS: The 5-year disease-free survival was 71.4%. Increasing tumor volume was associated with more frequent lymph node metastases and a significant decrease in OS (P = 0.0112). The Median tumor volume was smaller in stage IIa tumors than in stage Ib2 tumors, and histopathological stage did not correlate linearly with lymph node metastases as well as OS. Stage Ib2 tumors were associated with worse overall survival than stage IIa tumors. In univariate analysis, lymph node metastases, histopathological stage, lymph vascular space involvement, tumor volume, parametrial spread, and tumor involvement of resection margins were significant parameters for OS. In multivariate statistical analysis, only lymph node metastases and histopathological staging remained independent prognostic factors for OS. CONCLUSIONS: Tumor volume does not seem to confer additional prognostic information if histopathological stage and lymph node status are known. However, it may provide important prognostic information if lymph node status is not known or histopathological stage cannot be assessed.

Co-expression of tenascin-C and vimentin in human breast cancer cells indicates phenotypic transdifferentiation during tumour progression: correlation with histopathological parameters, hormone receptors, and oncoproteins.

Loss of epithelial morphology and the acquisition of mesenchymal characteristics are typical for carcinoma cells in tumour progression. In human breast carcinomas, up-regulation of tenascin-C (TN-C) and vimentin (Vim) is frequently observed in cancer cells and correlates with increased malignancy. Thus, it is possible that TN-C is co-expressed with Vim, representing cancer cells that have undergone epithelial-mesenchymal transition (EMT). This study examined 128 breast carcinomas using immunohistochemical techniques to demonstrate that mammary cancer cells are a prominent source of both TN-C and Vim. Statistical analysis revealed a significant association between TN-C and Vim expression in cancer cells. TN-C expression also correlated positively with overexpression of c-erbB-2 oncoprotein and down-regulation of oestrogen receptors (ERs). Eleven human mammary cancer cell lines and two 'normal' cell lines were examined by western blotting and immunohistochemistry. Co-expression of TN-C and Vim was detected in the carcinosarcoma cell line HS 578T, SK-BR-3 (B), fibroblast-like MDA-MB-231 cells, and the myoepithelial cell line HBL 100. These findings suggest that TN-C and Vim, when co-expressed in mammary carcinoma cells, represent regulator genes likely to be involved in EMT during mammary carcinogenesis.

Clinical relevance of HPV 16/18 testing methods in cervical squamous cell carcinoma.

Three different in situ hybridization (ISH) methods were compared for their clinical relevance and suitability in detecting human papillomavirus (HPV) 16/18 in 55 cases of squamous cell carcinoma (SCC) of the uterine cervix. After the initial biopsy, surgery, and/or radiation therapy, patients were followed for 5 to 8 years. A biotinylated cDNA probe for HPV 16/18 was applied to serial sections in combination with conventional streptavidin-biotin-peroxidase ISH (a widely applied routine procedure), streptavidin-Nanogold-silver ISH, and tyramide-signal amplified (TSA) streptavidin-Nanogold-gold ISH. The TSA principle is also known as catalyzed reporter deposition and is, apart from in situ PCR, probably today's most sensitive technique for detecting papillomavirus infection by microscopic means. Nearly 65.5% of the cases showed specific HPV 16/18 detection with TSA ISH, whereas 43.6% were positive with streptavidin-Nanogold-silver-ISH, and only 40.0% with peroxidase-based ISH. Statistical analyses comparing early and advanced stages in both HPV-positive and -negative groups revealed a significantly better outcome for early disease patients; statistical significance was most pronounced with TSA ISH. In a subgroup of patients who had received radiation therapy without prior surgery (n = 35), those with advanced disease were significantly less likely to have HPV 16/18 infection than those with early disease. A significantly better overall survival was observed in those women with HPV 16/18-positive carcinomas who had undergone surgery before radiation therapy (seen with all three methods). We conclude that TSA, in addition to being the most sensitive HPV in situ method applied in this study, gave the most significant and clinically relevant statistical results.