MAL is expressed in a subset of Hodgkin lymphoma and identifies a population of patients with poor prognosis.

Classical Hodgkin lymphoma (cHL) and mediastinal (thymic) large B-cell lymphoma (MLBL) have clinical, histopathologic, and molecular genetic similarities. MAL, a gene that encodes a protein associated with lipid rafts in T and epithelial cells, is overexpressed in a majority of MLBLs and has been reported in a minority of cHLs. To study the clinical significance of MAL in cHL, we immunostained 86 cases; 16 cHLs (19%) expressed MAL. Expression correlated with nodular sclerosis subtype, and within this subtype, with grade 2 histology. Univariable analysis revealed association of age of 45 years or older, MAL expression, and an International Prognostic Score of more than 2 with worse failure-free survival. Age of 45 years or older, MAL expression, and stage III or IV were associated with worse overall survival (OS). Cox proportional hazards modeling showed age (P = .04 and P = .03, respectively) and MAL expression (P = .03 and P = .01, respectively) as independent predictors of time to failure-free survival and OS. Stage showed borderline significance in OS (P = .08). MAL expression seems to identify a subset of cHL with an adverse outcome and provides additional evidence for a link between cHL and MLBL.

The "real-life" variability of CA-125 in ovarian cancer patients.

BACKGROUND: The serum CA-125 antigen value has proven to be useful in predicting changes that affect prognosis and management of ovarian cancer; however, interpreting variations in the tumor marker is still not well-defined. Our goal was to further understand the analytical variability of CA-125 in a conventional hospital laboratory. METHODS: In an IRB-approved study, ovarian and primary peritoneal cancer patients receiving active therapy at the Cleveland Clinic Foundation had a blood sample obtained prospectively during a routine clinic visit. The sample was separated into three aliquots then submitted on three different weekdays for CA-125 analysis. Laboratory personnel performing the CA-125 assays had no knowledge that this blood was part of a research study. The CA-125 assay used was a microparticle enzyme immunoassay from Abbott AxSYM system. RESULTS: Fifty-one blood samples were obtained from 45 patients (median age: 62; range: 45-89). The samples were stratified into 3 sub-groups: <100 U/ml (24 samples), 100-600 U/ml (15 samples), and >600 U/ml (12 samples). Analysis of CA-125 consisted of calculating the standard deviations (SD) and coefficients of variations (CV) for each patient's samples. The median SD for CA-125 <100 U/ml was 0.58, mean SD 1.14 +/- 2.44, median CV 1.49, and mean CV 2.93 +/- 4.43. The median SD for CA-125 100-600 U/ml was 4.51, mean SD 9.93 +/- 11.03, median CV 2.51, and mean CV 7.66 +/- 11.13. The median SD for CA-125 >600 U/ml was 56.12, mean SD 149.73 +/- 230.35, median CV 2.10, and mean CV 10.93 +/- 24.75. CONCLUSIONS: CA-125 assay imprecision can contribute considerably to result variations in a conventional laboratory setting, with the degree of variation being directly related to the absolute CA-125 value. However, the relative variability is fairly constant with a median of 1.5-2.5% of the CA-125 concentration.

The expression of fascin, an actin-bundling motility protein, correlates with hormone receptor-negative breast cancer and a more aggressive clinical course.

The invasion and metastasis of tumor cells is a major cause of mortality in cancer patients. In the current study, we investigated the expression of fascin, an actin-bundling motility-associated protein, in 210 invasive breast carcinomas with corresponding 5-year clinical follow-up. Fascin expression was compared with hormone receptor (ER/PR) status, HER2 status, cancer grade, cancer stage, metastasis pattern, disease-free survival, and overall survival. Fascin expression was seen in 16% (33/210) of the cases and correlated with ER negativity (22/33, P < 0.001), PR negativity (21/33, P < 0.001), Bloom-Richardson grade 3 (19/29, P < 0.001), and advanced stage (stage 3 or 4, P = 0.04). There was no correlation between fascin expression and HER2 status or pattern of metastases. Patients whose tumors were positive for fascin showed both a decreased mean disease-free survival (74.44 versus 100.52 months, P = 0.002) and mean overall survival (77.58 versus 98.98 months, P = 0.002), independent of tumor stage and HER2 status, but not independent of ER/PR status or cancer grade. Given fascin's role in altering cell motility, overexpression may contribute to a more aggressive clinical course in ER/PR-negative breast cancers. If so, then fascin may represent a new molecular target for therapeutic intervention in patients with ER-negative breast cancer.

Takayasu arteritis: utility and limitations of magnetic resonance imaging in diagnosis and treatment.

OBJECTIVE: Previous studies have confirmed the poor correlation of symptoms, signs, and levels of acute-phase reactants with disease activity in approximately 50% of all patients with Takayasu arteritis (TA). Invasive angiographic studies demonstrate vessel lumen anatomy, but do not provide qualitative information about the vessel wall. Moreover, sequential invasive angiographic studies expose patients to high-dose ionizing radiation and catheter/procedure-related morbidity. The aim of the present study was to determine the utility of new developments in vascular magnetic resonance (MR) technology in patients with TA. METHODS: Electrocardiogram-gated "edema-weighted" MR was used to evaluate the aorta and its primary branches with regard to the vascular lumen, vessel wall anatomy, and vessel wall edema in 24 TA patients (77 studies). Inclusion criteria were age <50 years and features of TA on both clinical examination and invasive angiographic studies. Patients were stratified based on clinical and laboratory indications of having either unequivocally active disease, inactive disease, or uncertain disease status. RESULTS: MR revealed vessel wall edema in 94% (17 of 18), 81% (13 of 16), and 56% (24 of 43) of studies obtained during periods of unequivocally active disease, uncertain disease activity, and apparent clinical remission, respectively. Westergren erythrocyte sedimentation rate and C-reactive protein values did not correlate with either the clinical assessment of disease activity or MR evidence of vascular edema. The frequency of presumed vascular inflammation (edema), as assessed by MR, in patients who appeared to be in remission was similar to the reported frequency of new angiographic lesions and histopathologic evidence of active disease in surgical specimens from patients thought to be in remission. However, the presence of edema within vessel walls did not consistently correlate with the occurrence of new anatomic changes found on subsequent studies. CONCLUSION: Inconsistencies in the presence or absence of vessel edema and subsequent anatomic changes have cast doubt on the utility of edema-weighted MR imaging as a sole guide to disease activity and treatment in TA. In this study, the greatest utility of MR was in providing a safe, noninvasive means of assessing changes in vascular anatomy.