Tumors of low malignant potential (LMP) represent 20% of epithelial ovarian cancers (EOCs) and are associated with a better prognosis than the invasive tumors (TOV). Defining the relationship between LMPs and TOVs remains an important goal towards understanding the molecular pathways that contribute to prognosis, as well as providing molecular markers, for these EOCs. To this end, DNA microarray analyses were performed either in a primary culture or a tumor tissue model system and selected candidate genes showing a distinctive expression profile between LMPs and TOVs were identified using a class prediction approach based on three statistical methods of analysis. Both model systems appear relevant as candidate genes identified by either model allowed the proper reclassification of samples as either LMPs or TOVs. Selected candidate genes (CAS, CCNE1, LGALS8, ITGb3, ATP1B1, FLIP, KRT7 and KRT19) were validated by real-time quantitative PCR analysis and show differential expression between LMPs and TOVs. Immunohistochemistry analyses showed that the two tumor classes were distinguishable by their expression of CAS, TNFR1A, FLIP, CKS1 and CCNE1. These results define signature patterns for gene expression of LMPs and TOVs and identify gene candidates that warrant further study to deepen our understanding of the biology of EOC.

Molecular profiling is a powerful approach to identify potential clinical markers for diagnosis and prognosis as well as providing a better understanding of the biology of epithelial ovarian cancer. On the basis of the analysis of HuFL expression data, we have previously identified genes that distinguish low malignant potential and invasive serous epithelial ovarian tumors. In this study, we used immunohistochemistry to monitor a subset of differently expressed candidates (Ahr, Paep, Madh3, Ran, Met, Mek1, Ccne1, Ccd20, Cks1 and Cas). A tissue array composed of 244 serous tumors of different grades (0–3) and stages (I–IV) was used in this analysis. All markers assayed presented differential protein expression between serous tumors of low and high grade. Significant differences in Ccne1 and Ran expression were observed in a comparison of low malignant potential and grade 1 tumor samples (p < 0.01). In addition, irrespective of the grade, Ccne1, Ran, Cdc20 and Cks1 showed significant differences of expression in association with the clinical stage of disease. While high level of Ccne1 have previously been associated with poor outcomes, here we found that high level of either Ran or Cdc20 appear to be more tightly associated with a poor prognosis (p < 0.001, 0.03, respectively). The application of these biomarkers in both the initial diagnosis and prognostic attributes of patients with epithelial ovarian tumors should prove to be useful in patient management. © 2006 Wiley‐Liss, Inc.

With low cure rates but increasing diverse treatment options that provide variable remission times, ovarian cancer is increasingly being recognized as a chronic disease. This reality indicates the need for a better understanding of factors influencing disease progression. In a previous global analysis of gene expression, we identified genes differentially expressed when comparing serous epithelial ovarian tumors of low and high malignant potential (grade 0 vs grade 3). In this analysis, 4 out of 5 members of the SET complex, SET, APE1, NM23 and HMGB2, were highly expressed in invasive grade 3 tumors. To further investigate the expression of these genes and the fifth member of the SET complex (pp32), we performed immunohistochemistry, on a tissue array composed of 235 serous tumors of different grades and disease stages. A significant correlation between expression of all SET complex proteins and the tumor differentiation was observed (p < 0.05). When combining all tumors, overexpression of Nm23 (p = 0.04), Set (p = 0.004) and Ape1 (p = 0.004) was associated with the clinical stage of the disease. No marker by itself was associated with prognosis. The combination of a high level of Nm23 in the context of a low level of Set compared to all other combinations of these markers did confer a better prognosis (p = 0.03). When combined, high expression of Hmgb2 and low expression of Ape1 was also associated with patient prognosis (p = 0.05). These findings suggest that a strategy that sums the activities of different partners within a pathway may be more appropriate in designing nomograms for patient stratification. © 2006 Wiley‐Liss, Inc.

BACKGROUND Metastatic tumors to the salivary glands are common, but documentation in the cytologic literature has been limited. The current study presents the authors' experience with fine‐needle aspiration (FNA) in metastatic nonlymphomatous tumors to the salivary glands. METHODS From a retrospective review of 1675 salivary gland lesions (1535 patients), the authors collected 40 salivary gland lesions (39 patients who had histories of extrasalivary cancer) that were diagnosed cytologically as metastases to the salivary glands and were correlated histologically. RESULTS FNAs of 34 parotid gland and 6 submandibular gland tumors were performed. The cytologic diagnoses of metastases of squamous cell carcinoma (15 cases), melanoma (12 cases), carcinoma (5 cases), rhabdomyosarcoma (3 cases), and retinoblastoma (2 cases) were confirmed (95%) histologically. Two (5%) FNAs were false‐negative. CONCLUSIONS In patients who had a history of extrasalivary cancer, cytology examination was very helpful and sufficient for adequate patient management. Cancer (Cancer Cytopathol) 2000;90:350–356. © 2000 American Cancer Society.

Protein‐imprinted soft‐gel composite microspheres with magnetic susceptibility (MS‐PIGMs) were prepared by inverse suspension polymerization using Fe3O4 particles as magnetically susceptible component and bovine serum albumin and lysozyme (Lyz) as templates, respectively. The average content of magnetically susceptible component (Fe3O4) inside MS‐PIGMs was determined using thermogravimetric analyzer, and the magnetic characteristics of MS‐PIGMs were measured by vibrating sample magnetometer. The results showed that the resulting MS‐PIGMs had a certain magnetic response to external magnetic fields, and their average content of Fe3O4 was 2.08%. Their recognition specificity was investigated using BSA and Lyz as both templates and control molecules and characterized by high‐performance liquid chromatography, and the mechanism of imprinting and recognition was analyzed. It was shown that the resulting BSA imprinted soft‐gel composite microspheres with magnetic susceptibility (BSA‐PIGMs) and Lyz imprinted soft‐gel composite microspheres with magnetic susceptibility (Lyz‐PIGMs). All exhibited good recognition selectivity for their templates, and the relative separation factor (β) was 4.75 and 5.88, respectively. The recognition selectivity of MS‐PIGMs to their templates depended mainly on the synergic action of a large quantity of hydrogen binding being caused by complementation and very close contact of outer surface of proteins with inner surface of “imprinting cavities.” © 2005 Wiley Periodicals, Inc. J Appl Polym Sci, 2006