Breast Carcinoma Cells in Primary Tumors and Effusions Have Different Gene Array Profiles

The detection of breast carcinoma cells in effusions is associated with rapidly fatal outcome, but these cells are poorly characterized at the molecular level. This study compared the gene array signatures of breast carcinoma cells in primary carcinomas and effusions. The genetic signature of 10 primary tumors and 10 effusions was analyzed using the Array-Ready Oligo set for the Human Genome platform. Results for selected genes were validated using PCR, Western blotting, and immunohistochemistry. Array analysis identified 255 significantly downregulated and 96 upregulated genes in the effusion samples. The majority of differentially expressed genes were part of pathways involved in focal adhesion, extracellular matrix-cell interaction, and the regulation of the actin cytoskeleton. Genes that were upregulated in effusions included KRT8, BCAR1, CLDN4, VIL2, while DCN, CLDN19, ITGA7, and ITGA5 were downregulated at this anatomic site. PCR, Western blotting, and immunohistochemistry confirmed the array findings for BCAR1, CLDN4, VIL2, and DCN. Our data show that breast carcinoma cells in primary carcinomas and effusions have different gene expression signatures, and differentially express a large number of molecules related to adhesion, motility, and metastasis. These differences may have a critical role in designing therapy and in prognostication for patients with metastatic disease localized to the serosal cavities

Endoglin (CD105) expression in ovarian serous carcinoma effusions is related to chemotherapy status

Endoglin (CD105), a cell surface co-receptor for transforming growth factor-β, is expressed in proliferating endothelial cells, as well as in cancer cells. We studied endoglin expression and its clinical relevance in effusions, primary tumors, and solid metastatic lesions from women with advanced-stage ovarian serous carcinoma. Endoglin expression was analyzed by immunohistochemistry in effusions (n = 211; 174 peritoneal, 37 pleural). Cellular endoglin staining was analyzed for association with the concentration of soluble endoglin (previously determined by ELISA) in 95 corresponding effusions and analyzed for correlation with clinicopathologic parameters, including survival. Endoglin expression was additionally studied in 34 patient-matched primary tumors and solid metastases. Carcinoma and mesothelial cells expressed endoglin in 95/211 (45%) and 133/211 (63%) effusions, respectively. Carcinoma cell endoglin expression was more frequent in effusions from patients aged ≤60 years (p = 0.048) and in post- compared to prechemotherapy effusions (p = 0.014), whereas mesothelial cell endoglin expression was higher in prechemotherapy effusions (p = 0.021). No association was found between cellular endoglin expression and its soluble effusion concentration. Endoglin was expressed in 17/34 (50%) primary tumors and 19/34 (56%) metastases, with significantly higher percentage of immunostained cells in solid metastases compared to effusions (p = 0.036). Endoglin expression did not correlate with survival. Tumor cell endoglin expression is higher in post- vs. prechemotherapy effusions, whereas the opposite is seen in mesothelial cells. Together with its upregulation in solid metastases, this suggests that the expression and biological role of endoglin may differ between cell populations and change along tumor progression in ovarian carcinoma

MMP-7 is a highly specific negative marker for benign and malignant mesothelial cells in serous effusions

The aim of this study was to analyze the diagnostic role of MMP-7 in effusion cytology. Effusions (n = 356), consisting of 307 carcinomas (184 ovarian, 55 breast, 32 lung, 36 carcinomas of other origin) and 49 malignant mesotheliomas, were analyzed for MMP-7 expression using immunohistochemistry. MMP-7 was expressed in 124/307 (40%) carcinomas and was uniformly absent in malignant mesotheliomas (0/49; 0%; P <.001). Reactive mesothelial cells were similarly MMP-7 negative in all carcinoma specimens. In carcinomas, expression was most frequent in tumors of ovarian and other female genital (cervical and endometrial) origin (P <.001). The sensitivity and specificity of this marker in the differential diagnosis between high-grade serous carcinoma and malignant mesothelioma were 46% and 100%, respectively. In conclusion, MMP-7 expression is highly specific, though only of moderate sensitivity, for the diagnosis of carcinoma in the differential diagnosis from both benign and malignant mesothelial cells