BACKGROUND.Growth factor receptors and cell signaling factors play a crucial role in human carcinomas and have been studied in ovarian tumors with varying results. Cell signaling involves multiple pathways and a myriad of factors that can be mutated or amplified. Cell signaling is driven through the mammalian target of rapamycin (mTOR) and extracellular regulated kinase (ERK) pathways and by some downstream molecules, such as 4E binding protein 1 (4EBP1), eukaryotic initiation factor 4E, and p70 ribosomal protein S6 kinase (p70S6K). The objectives of this study were to analyze the real role that these pathways play in ovarian cancer, to correlate them with clinicopathologic characteristics, and to identify the factors that transmit individual proliferation signals and are associated with pathologic grade and prognosis, regardless specific oncogenic alterations upstream.METHODS.One hundred twenty‐nine ovarian epithelial tumors were studied, including 20 serous cystadenomas, 7 mucinous cystadenomas, 11 serous borderline tumors, 16 mucinous borderline tumors, 29 serous carcinomas, 16 endometrioid carcinomas, 15 clear cell carcinomas, and 15 mucinous carcinomas. Tissue microarrays were constructed, and immunohistochemistry for the receptors epidermal growth factor receptor (EGFR) and c‐erb‐B2 was performed and with phosphorylated antibodies for protein kinase B (AKT), 4EBP1, p70S6K, S6, and ERK.RESULTS.Among 129 ovarian neoplasms, 17.8% were positive for c‐erb‐B2, 9.3% were positive for EGFR, 47.3% were positive for phosphorylated AKT (p‐AKT), 58.9% were positive for p‐ERK, 41.1% were positive for p‐4EBP1, 26.4% were positive for p70S6K, and 15.5% were positive for p‐S6. Although EGFR, p‐AKT, and p‐ERK expression did not differ between benign, borderline, or malignant tumors, c‐erb‐B2, p‐4EBP1, p‐p70S6K, and p‐S6 were expressed significantly more often in malignant tumors. Only p‐4EBP1 expression demonstrated prognostic significance (P = .005), and only surgical stage and p‐4EBP1 expression had statistical significance in the multivariate analysis.CONCLUSIONS.In patients with ovarian carcinoma, significant expression of p‐4EBP1 was associated with high‐grade tumors and a poor prognosis, regardless other oncogenic alterations upstream. This finding supports the study of this factor as a hallmark or pivotal factor in cell signaling in ovarian carcinoma that may crucial in the transmission of the proliferation cell signal and may reflect the real oncogenic role of this pathway in ovarian tumors. Cancer 2006. © 2006 American Cancer Society.

We conducted the current study to characterize the clinical presentation of primary Sjögren syndrome (SS) in a large cohort of Spanish patients and to determine whether epidemiologic, clinical, and analytical features modulate disease expression. Patients were from the GEMESS Study group, which was formed in 2005 and included 12 Spanish reference centers. By March 2007, the database included 1010 consecutive patients, recruited since 1994, both incident and prevalent cases. The cohort included 937 women and 73 men (ratio, 13:1), with a mean age of 53 years at diagnosis and 59 years at inclusion in the registry. Multivariate analysis showed that male patients had a lower frequency of thyroiditis, Raynaud phenomenon, and antinuclear antibodies. Young-onset patients had a low degree of sicca involvement (xerostomia and parotid enlargement) and a high frequency of immunologic markers (anti-Ro/SS-A and low C4 levels). Patients with disease duration of more than 10 years had a higher prevalence of xerophthalmia, parotid enlargement, lung involvement, and peripheral neuropathy in comparison with incident cases. The subset of patients with anti-Ro/La antibodies had the highest prevalence of most systemic, hematologic, and immunologic alterations (higher frequency of Raynaud phenomenon, altered parotid scintigraphy, positive salivary gland biopsy, peripheral neuropathy, thrombocytopenia, and rheumatoid factor). Hypocomplementemia was associated with a higher frequency of vasculitis and lymphoma, and cryoglobulins with a higher frequency of parotid enlargement, vasculitis, and leukopenia.Epidemiologic, clinical, and analytical features have a significant impact on the clinical presentation of primary SS, influencing the results of the main diagnostic tests, the prevalence and diversity of extraglandular involvement, and the frequency of the main immunologic markers. Primary SS should be considered as a systemic autoimmune disease that can express in many guises beyond sicca involvement.

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SUMMARY Because thrombocytopenia occurs frequently in patients with anticardiolipin (aCL) antibodies and thrombosis, some investigators have proposed that aCL antibodies may play a direct part in thrombosis by binding and activating platelets. To test this proposal experiments were performed to determine whether aCL antibodies can bind platelets. Preincubation of aCL positive sera with freeze-thawed platelets caused significant inhibition of aCL activity in four serum samples tested. Antibodies with cardiolipin binding activity were subsequently eluted from these platelets. Total phospholipids extracted from platelets inhibited aCL activity, and the specific phospholipids bound were shown to be phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol. It is concluded that aCL antibodies can bind phospholipids in platelet membranes but pertubation of the membrane must first occur.

ISRCTN81818945; http://isrctn.org/.

The antiphospholipid antibodies present in antiphospholipid syndrome (APS) are directed at a number of phospholipid-binding proteins: b 2 glycoprotein I (b 2 GPI), prothrombin, and so on. Antibodies directed at b 2 GPI are accepted as a classification criterion for APS, while the presence of antiprothrombin antibodies is not. In the present article, we investigated the possible role of antiphosphatidylserine/prothrombin antibodies (aPS/PT) as marker of APS on a cohort of 295 individuals with APS (95 primary APS and 45 secondary APS) and APS-related diseases. We found aPS/PT to be highly associated with venous thrombosis (immunoglobulin G [IgG] aPS/ PT odds ratio [OR], 7.44; 95% confidence interval [CI], 3.97-13.92 and IgM aPS/PT OR, 2.54; 95% CI, 1.35-4.77) and obstetric abnormalities (IgG aPS/PT OR, 2.37; 95% CI, 1.04-5.43), but not with arterial thrombosis. A very high degree of concordance between the concentration of aPS/PT and lupus anticoagulant activity was demonstrated. Therefore, we support the inclusion of aPS/PT determination as second-level assay to confirm APS classification.

SUMMARY Chorea is a rare manifestation of systemic lupus erythematosus (SLE). In this report the clinical features of two cases of chorea associated with SLE are presented. Of special interest were the raised titres of antiphospholipid antibodies in both cases. The possible pathogenic role of these antibodies is briefly discussed.