These data suggest that antibodies directed against the gamma2 chain of laminin-5 can identify cervical lesions with invasive capacity and thus may be useful as a sensitive marker of early invasion.

Studies of multiple markers in tumors are required for adequate biological characterization. We have characterized the expression of multiple proteins in human ovarian tumors using the technique of 2‐dimensional gel electrophoresis (2‐DE/PDQUEST). Tumor cells were prepared from the tissue of 22 ovarian tumors. Large variations were observed between tumors in the expression of various polypeptides, indicating heterogeneity in gene expression. An increase in the spot density of 2 cell‐cycle‐related proteins, PCNA and OP18/stathmin, was observed in carcinomas. Borderline tumors expressed low levels of these proteins. Significant increases in the levels of nm23, GST‐π, elongation factor 2 and triose phosphate isomerase were recorded in ovarian carcinomas. Furthermore, decreases in the levels of tropomyosin‐2 and lamin C were observed in malignant as compared with benign tumors. The pattern of expression of 9 protein markers was examined in individual tumors. All malignant tumors showed simultaneous alterations in the expression of 5 or more of these proteins, whereas no benign tumor showed alterations in the expression of more than 3 polypeptides. Borderline tumors showed alterations in 0 to 6 markers. We conclude that the simultaneous analysis of multiple polypeptides, which can be achieved by 2‐DE, is useful for characterization of gene expression and diagnostic studies in ovarian tumors. Int. J. Cancer 73:678–683, 1997© 1997 Wiley‐Liss, Inc.

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Ovarian tumors range from benign to aggressive malignant tumors, including an intermediate class referred to as borderline carcinoma. The prognosis of the disease is strongly dependent on tumor classification, where patients with borderline tumors have much better prognosis than patients with carcinomas. We here describe the use of hierarchical clustering analysis of quantitative protein expression data for classification of this type of tumor. An accurate classification was not achieved using an unselected set of 1,584 protein spots for clustering analysis. Different approaches were used to select spots that were differentially expressed between tumors of different malignant potential and to use these sets of spots for classification. When sets of proteins were selected that differentiated benign and malignant tumors, borderline tumors clustered in the benign group. This is consistent with the biologic properties of these tumors. Our results indicate that hierarchical clustering analysis is a useful approach for analysis of protein profiles and show that this approach can be used for differential diagnosis of ovarian carcinomas and borderline tumors. © 2002 Wiley-Liss, Inc. Key words: borderline ovarian tumors; hierarchical cluster analysis; molecular classificationMost ovarian carcinomas arise from the mesothelial surface lining of the ovaries (for a review, see Feeley and Wells 1 ). The major subtypes consist of serous/seropapillary and mucinous tumors. Ovarian tumors range from benign tumors without nuclear atypia or stromal invasion to carcinomas showing both these characteristics. An intermediate group of tumors, referred to as borderline carcinomas, can be distinguished. These tumors, which represent about 6% of all ovarian epithelial tumors, have a low rate of growth, a low potential to invade or metastasize and may show nuclear atypia or stromal invasivity (not both). 2 Patients with borderline tumors have significantly better prognosis than patients with epithelial ovarian cancer, 3 and early-stage disease is treated with surgery alone.Studies on gene and protein expression profiling have the potential to provide better insight into complex biologic processes. Eisen et al. 4 have described a method of cluster analysis to describe the similarity between samples based on their pattern of expression of a large number of genes. Gene expression profiling has been performed using cDNA micro arrays. 5 This approach has been used for molecular classification of various forms of cancer 6 -9 and cancer cell lines. 10 The aim of our study was to analyze 2-dimensional gel electrophoresis (2-DE) protein expression profiles by the hierarchical clustering method in order to classify ovarian tumors as benign, borderline and malignant. To have sufficient follow-up, we used tumors analyzed 2-6 years ago and previously subjected to partial least square discriminant analysis (PLS-DA). 11

The incidence of secondary endometrial cancer reported in this study following treatment of breast cancer patients with tamoxifen at doses of 40 mg/d in a large clinical trial is higher than that reported for previous large trials of tamoxifen at doses of 20 mg/d. Thus, tamoxifen dosage may be a critical factor in the subsequent occurrence of endometrial cancer. Our results also suggest two important considerations for improved follow-up in long-term tamoxifen trials: careful registration of second cancers and routine gynecologic examinations to ensure early detection of endometrial cancer.