Combination of Cytology, Fluorescence In Situ Hybridization for Aneuploidy, and Reverse-Transcriptase Polymerase Chain Reaction for Human Mammaglobin/Mammaglobin B Expression Improves Diagnosis of Malignant Effusions

Abstract

Molecular techniques are definitely useful to detect malignancy in cytologically negative effusions. Tumor cell detection in effusions can be significantly improved by FISH and PCR techniques applying appropriate molecular markers. This finding should help to improve tumor staging, prognostic assessment, and treatment monitoring.

Normalization of the Ovarian Cancer Microenvironment by SPARC

“…Our previous findings that ascitic fluid from SP À/À mice enhanced the invasiveness and, to a lesser extent, the adhesion of ID8 cells (25) led us to investigate the possible mechanisms by which SPARC modulates the interplay of VEGF and MMPs in the milieu of the ascitic fluid. Consistent with our earlier report, the difference between SP +/+ and SP À/À ascitic fluid -induced adhesion was found to be insignificant but markedly inhibited by a VEGF neutralizing antibody, sFlt [2][3][4][5][6][7][8][9][10][11] , and a VEGFR2 (KDR) tyrosine kinase inhibitor, suggesting an autocrine effect of VEGF produced by ID8 cells themselves (Fig. 3A).…”

“…C. Basal adhesion of ID8 cells to fibronectin was measured after pretreatment with SPARC (20 Ag/mL, 2 h), VEGF neutralizing antibody, Flt [2][3][4][5][6][7][8][9][10][11] , and KDR2 inhibitor IV as described above. D. Basal fibronectin invasion by ID8 cells after pretreatment with SPARC, VEGF neutralizing antibody, Flt [2][3][4][5][6][7][8][9][10][11] , and KDR2 inhibitor IV was done exactly as described in (A). ID8-VEGF cell adhesion to (E) and invasion of (F) fibronectin were tested as described above.…”

“…The ability of floating ovarian cancer cells in these malignant effusions to survive, proliferate, and disseminate in the absence of immediate proximity to a solid scaffold and vascular structures has been attributed to the unique, yet poorly defined, permissive microenvironment of these dense exudative fluids (1). The high autonomous proliferation rate of the metastatic ovarian cancer cells, their ability to develop alternative means of survival, as well as the contributions of inflammatory cells present in malignant effusions are believed to be responsible for the pluoripotent nature of these malignant effusions (2)(3)(4)(5). Ovarian cancer cells and peritoneal mesothelial cells constitutively produce bioactive lipids and cytokines that further promote motogenesis and mitogenesis of ovarian cancer cells in both autocrine and paracrine fashion (6)(7)(8)(9).…”

Sensitive detection of tumour cells in effusions by combining cytology and fluorescence in situ hybridisation (FISH)

“…The study presented here includes an updated series of 358 effusion specimens, of which various cytological and molecular aspects have already been previously published (Fiegl et al, 2000(Fiegl et al, , 2004.…”

“…Thus, new diagnostic approaches are warranted to enhance the sensitivity and specificity of tumour cell detection in effusions. We and others used fluorescence in situ hybridisation (FISH) to sensitively detect tumour cells regularly characterised by numeric chromosomal aberrations (Fiegl et al, 2000(Fiegl et al, , 2004van Oostenbrugge et al, 2000). By identification of tumour-associated aneuploidy, FISH analysis has been successfully applied in tumour aspirates, urine, cerebrospinal fluid, cervical smears, sputum, and effusions (Cajulis et al, 1994;Chen et al, 1995;Ichikawa et al, 1996;Schenk et al, 1997;Mian et al, 1999;Fiegl et al, 2000Fiegl et al, , 2004van Oostenbrugge et al, 2000).…”