Mycosis fungoides (MF) is the most common type of primary cutaneous T-cell lymphoma (CTCL). To identify a molecular signature characteristic of MF tumor stage, we used a bioinformatic approach... Show moreMycosis fungoides (MF) is the most common type of primary cutaneous T-cell lymphoma (CTCL). To identify a molecular signature characteristic of MF tumor stage, we used a bioinformatic approach involving meta-analysis of publicly available gene expression data sets combined with previously generated gene expression data. Results for a selection of genes were further refined and validated by quantitative PCR and inclusion of additional controls. With this approach, we identified a profile specific for MF tumor stage, consisting of 989 aberrantly expressed genes, the majority of which (718 genes) are statistically significantly more expressed in MF compared with normal skin, inflamed skin, and normal T cells. As expected, the signature contains genes reflecting the highly proliferative characteristic of this T-cell malignancy, including altered expression of cell cycle and kinetochore regulators. We uncovered details of the immunophenotype, suggesting that MF originates from IL-32-producing cells and identified previously unreported therapeutic targets and/or diagnostic markers, for example, GTSF1 and TRIP13. Loss of expression of the NF-κB inhibitor, NFKBIZ, may partly explain the enhanced activity of NF-κB, which is a hallmark of MF and other CTCLs. Show less
A tumor in the parametria, either continuous with or separate from the primary malignancy, is an unfavorable prognostic factor in cervical cancer. The incidence of a parametrial tumor localized in... Show moreA tumor in the parametria, either continuous with or separate from the primary malignancy, is an unfavorable prognostic factor in cervical cancer. The incidence of a parametrial tumor localized in blood or lymph vessels, or in tissue, and the relationship of these involvement patterns with pathologic characteristics and prognosis were investigated. Seventy-nine of 763 surgically treated cervical cancer patients (10%) had a tumor in the parametria in hysterectomy specimens. The available patient material was reviewed to discriminate between continuous and discontinuous parametrial tumor growth. The involvement pattern for discontinuous growth was specified on the basis of immunohistochemical staining with different specific markers. Fifty percent of the parametrial tumor involvement found postoperatively was caused by continuous extension of the primary process into the parametria. In the other 50%, the parametrial tumor was separate from the primary process. In this discontinuous group, we found a frequent presence of tumor in the lymph nodes and/or lymph vessels (together 79%) and even a rare appearance of tumor in the blood vessels (14%). A tumor was further found in unspecified vessels in 2 patients (5%), and as isolated foci in 6 patients (14%). Fourteen patients (33%) had more than 1 involvement pattern. Positive pelvic lymph nodes were more frequent in the discontinuous group. The involvement pattern was no independent predictor of overall survival. Parametrial blood vessel involvement was related to the development of distant metastases. The majority (79%) of parametrial involvement in the discontinuous group is caused by lymphatic metastases. Parametrial blood vessel involvement might be an independent predictor for the development of distant metastasis. Show less
