Breast lesions: correlation of contrast medium enhancement patterns on MR images with histopathologic findings and tumor angiogenesis

PURPOSE: To compare qualitative and quantitative magnetic resonance (MR) mammographic features of breast lesions with histopathologic findings, especially tumor angiogenesis. MATERIALS AND METHODS: Seventy-three patients (72 women, one man; aged 30-78 years; mean age, 51.0 years) with suspicious breast lesions underwent MR imaging. Noncontrast medium-enhanced localization imaging and then gadolinium-enhanced dynamic fast spoiled gradient-recalled-echo (SPGR) imaging were performed in all patients. In selected patients, subtraction fast SPGR images were obtained. The Pearson and Spearman correlation tests were used to determine the strength of the relationships between enhancement parameters and microvessel determinations. RESULTS: Time intensity curve type correlated with microvessel density grade (Spearman rank correlation test: r = .90, P < .001). The steepest slope of contrast medium uptake correlated with microvessel counts (Pearson correlation test; r = .83, P < .001). Peripheral enhancement in invasive carcinomas (n = 9) correlated with high peripheral and low central microvessel densities, which were associated with desmoplasia and/or necrosis. Internal septations (n = 2) were seen only in fibroadenomas. CONCLUSION: The density and distribution of microvessels may play major roles in the determination of the initial rate of contrast medium uptake and the heterogeneity of tumor enhancement.     

Tumor imaging with a macromolecular paramagnetic contrast agent: gadopentetate dimeglumine-polylysine

RATIONALE AND OBJECTIVES: We evaluated magnetic resonance (MR) contrast enhancement of tumor tissue following injection of the macromolecular conjugate, gadopentetate dimeglumine-polylysine. METHODS: T1-weighted MR imaging scans were performed on female Fisher-344 rats with subcutaneously implanted mammary adenocarcinoma tumors. Following the baseline scan, gadopentetate dimeglumine-polylysine or gadopentetate dimeglumine was injected at a dose of 0.1 mmol gadolinium per kilogram. RESULTS: Gadopentetate dimeglumine-polylysine injection resulted in a maximum enhancement of tumor contrast of 310 +/- 60% (n = 7). Tumor tissue remained enhanced and well defined for several days after gadopentetate dimeglumine-polylysine injection. Gadopentetate dimeglumine injection at the same dose resulted in a 70 +/- 25% (n = 4) maximal tumor enhancement and a corresponding 25 +/- 4% muscle enhancement. CONCLUSION: Gadopentetate dimeglumine-polylysine provides higher, more sustained tumor contrast than does gadopentetate dimeglumine for the same dosage of gadolinium.     

Factumycin and its new derivative RK-1009 enhance threonine-phosphorylation of a 60-kDa protein in Streptomyces griseus

Proliferative activity in renal cell carcinomas seems to be a significant predictor of prognosis independent of tumor stage and grade; its correlation with tumor type is not as well studied. We performed immunohistochemical analysis with antibodies directed against Ki67 (MIB1), cyclin A, and cyclin E on 44 renal tumors, including 2 metanephric adenomas, 9 oncocytomas, and 33 renal cell carcinomas, including 10 clear cell, 11 papillary, 6 chromophobe, and 6 sarcomatoid tumors. MIB1 and cyclin A stained between 0 and 23% of tumor nuclei. Reactivity for cyclin E was rare. There was a positive correlation between reactivity for MIB1 and for cyclin A (Spearman rank correlation r = .3587). Reactivity for either MIB1 or cyclin A did not correlate with tumor type, stage, or grade, but reactivity for MIB1 was significantly higher in patients older than 60 years than in patients 60 years of age or younger (P = .046). Proliferative activity as defined by either MIB1 or cyclin A is independent of tumor type, grade, or stage. The proliferative activity of benign renal tumors (metanephric adenoma and oncocytoma) was not significantly different than that seen in renal cell carcinoma.     

Comparison of gadopentetate dimeglumine and albumin-(Gd-DTPA)30 for microvessel characterization in an intracranial glioma model

To compare the performance of macromolecular albumin gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)30 and low molecular weight gadopentetate dimeglumine for microvessel characterization, we examined an intracranial 9L glioma model in which increased angiogenesis, hypervascularity, and hyperpermeability mimic characteristics of clinical malignant brain tumors. Dynamic MRI data were analyzed using a bidirectional, two-compartment kinetic model to extract quantitative estimates for fractional blood volume (fBV) and permeability surface area product (PS). Three criteria were used for comparison of contrast agent performance: (a) tumor conspicuity, defined as the contrast-to-noise ratio (CNR); (b) dynamic range of differential permeability estimates between tumor and normal brain; (c) reasonableness of blood volume estimates. Gadopentetate was superior to macromolecular albumin-(Gd-DTPA)30 for detection of 9L brain gliomas and for measurements of hyperpermeability.     

Mucoepidermoid carcinoma of the major salivary glands: clinical and histopathologic analysis of 234 cases with evaluation of grading criteria

BACKGROUND: The authors had previously conducted an investigation of minor salivary gland mucoepidermoid carcinoma, in which they demonstrated that certain clinical and histopathologic features were useful in predicting biologic outcome. The current study investigated the usefulness of these features in determining the prognoses of patients with mucoepidermoid carcinomas of the major salivary glands. METHODS: Clinical data and 15 histopathologic features were compared in 4 patient groups based on outcome after initial treatment. The outcome groups were 1) survival without disease, 2) survival with tumor recurrence only, 3) survival with metastasis, and 4) death related to tumor. A numeric score was assigned to each unfavorable histopathologic feature. Low grade tumors had scores of 0-4. Intermediate grade tumors scored 5 or 6. High grade tumors had scores higher than 6. RESULTS: Most patients (75%) were tumor free after the initial treatment. Twenty-one patients (9%) had local recurrence only, 12 (5%) demonstrated metastasis and survived, and 25 patients (11%) died of their disease. CONCLUSIONS: Clinical features associated with metastasis or death were more advanced age, tumor size, and preoperative symptoms. Histopathologic features that correlated with poor outcome were cystic component less than 20%, 4 or more mitotic figures per 10 high-power fields, neural involvement, necrosis, and anaplasia. All five of these histopathologic features demonstrated statistical prognostic significance when parotid gland tumors from Groups 1 and 4 were compared (P < 0.001). The point-based grading system demonstrated a statistically significant correlation with outcome for parotid tumors but not for submandibular tumors. The authors' findings indicate that patients with tumors of equal histopathologic grade have a better prognosis when their tumors are in the parotid gland than when their tumors are in the submandibular gland. Six of eight submandibular tumors that metastasized or resulted in death were low grade lesions, and none were high grade.     

Breathing during sleep in patients with nocturnal desaturation

BACKGROUND: The global DNA methylation of 136 breast lesions (117 primary invasive carcinomas, 5 benign phyllodes tumors, 11 fibroadenomas, and 3 sclerosing adenosis) and their respective adjacent parenchyma was analyzed using an in vitro enzyme assay. METHODS: In the group of patients with breast carcinoma, DNA hypomethylation was correlated with clinical and pathologic parameters known to affect disease prognosis. Histopathologic type, disease stage, and tumor grade were evaluated according to the World Health Organization classification, the TNM system, and the criteria of Elston and Ellis' criteria, respectively. DNA flow cytometry was performed in fresh/frozen samples stained with propidium iodide. Hormone receptor (estrogen and progesterone receptor) status was determined by immunocytochemistry. RESULTS: The comparative study of DNA methylation showed that the DNA of breast carcinomas was statistically significantly less methylated than the DNA of the respective adjacent parenchyma (P=0.0001), the DNA of breast benign lesions (P=0.0002), and the DNA of normal parenchyma (P < 0.0001). A statistically significant correlation was found between the global DNA hypomethylation and the disease stage (P=0.0009), tumor size (P=0.0026), and histologic grade (P=0.0097) of malignant neoplasms. A trend for DNA from breast carcinomas with positive axillary lymph nodes (N1) to be more hypomethylated than those without nodal involvement (NO) (P=0.055) was verified. In contrast, no significant association was found between DNA methylation and histologic type of tumors, hormone receptors, DNA ploidy, and S-phase fraction. CONCLUSIONS: The current shows that DNA hypomethylation is increased in breast carcinomas, playing a potentially important role in tumor development. These findings also suggest that DNA methylation status may be a biologic marker with prognostic significance in this group of neoplasms.     

Clinical comparison of the Alcon 20,000 Legacy and 10,000 Master phacoemulsification units

OBJECTIVES: To determine the relationship between angiogenesis and various histopathologic features as well as clinical outcome in patients with localized renal cell carcinoma (RCC). METHODS: Microvessel density was quantified by using immunocytochemical staining of endothelial cells for factor VIII-related antigen of 36 specimens taken from patients with pathologic Stage pT1 or pT2 RCC. All patients underwent radical nephrectomy and were followed for a mean time of 97.3 months. RESULTS: No association was noted between microvessel count (MVC) and either cell type, architecture, or tumor size. Inverse correlation was noted between MVC and nuclear area (P = 0.006), nuclear elipticity (P = 0.016), nuclear roughness (P = 0.039), and histologic grade (P = 0.047). Patients having tumors with low MVC had significantly better survival rate compared with those with high MVC neoplasms (P = 0.0014, by Cox proportional hazards method). CONCLUSIONS: Despite lack of correlation with known predictors of survival, MVC provides independent prognostic information for patients with localized RCC.     

Expression of the plasminogen activation system in kidney cancer correlates with its aggressive phenotype

Malignant tumors contrast with benign ones in their ability to invade adjacent tissue and to metastasize. The urokinase plasminogen activator is a proteolytic enzyme that can facilitate these processes. In many carcinomas, the concentration of the urokinase plasminogen activator system is high. The high expression of these enzymes is related to tumor grade. In this study, we have investigated whether secretion of the urokinase plasminogen activator, urokinase plasminogen activator receptor, and plasminogen activator inhibitor 1 in normal kidney tissue and kidney cancer tissue follows this pattern. We have found that urokinase plasminogen activator, urokinase plasminogen activator receptor, and plasminogen activator inhibitor 1 were expressed in higher levels in kidney cancers (squamous cell carcinoma and renal cell carcinoma) than in normal kidney tissue and that these differences were statistically significant (P < or = 0.05). In renal cell carcinomas, we have observed differences between normal kidney tissue and renal cell carcinomas in males and Caucasians but not in females and African Americans (P < or = 0.05). Expression of the urokinase plasminogen activator system was also higher in grade III tumors when compared with lower-grade tumors or normal tissue.     

Apoptosis loss and bcl-2 expression: key determinants of lymph node metastases in T1 breast cancer

The Bcl-2 proto-oncogene extends cell survival but does not confer any proliferative advantage to cells that express it. Thus, the loss of apoptosis may have a role in progression allowing the acquisition of additional mutations. To determine whether apoptosis loss at diagnosis is associated with the metastatic advantage of ductal breast carcinomas and to examine the relationship between Bcl-2 expression, p53, and tumor cell death status, we examined tumor samples from 116 patients diagnosed with T1 (2 cm or less) breast cancer with (n = 49) or without (n = 67) lymph node metastases. Apoptosis loss in histological sections was considered when <1% of tumor nuclei were stained with terminal deoxynucleotidyl transferase labeled with biotin. We studied the expression of Bcl-2 and p53 by immunohistochemistry and in 37 p53 mutations by single-strand conformational polymorphism analysis and cycle sequencing. Multivariate logistic regression modeling was used to estimate prevalence odds ratios (pORs) for apoptosis loss and presence of lymph node metastases. Patients with marked apoptosis loss in their tumor cells were about 5 times more likely to present lymph node metastases than those with no apoptosis loss in their tumor cells (adjusted pOR, 4.7; 95% confidence interval, 1.4-15.6; trend test, P = 0.008). Bcl-2 expression was strongly associated with both apoptosis loss (pOR, 6.9; trend test, P < 0.0001) and presence of lymph node metastases (pOR, 5.7; trend test, P = 0.002). These associations were more evident in histological grade I and II tumors than in poorly differentiated histological grade III tumors and in p53-negative tumors than in p53-positive tumors. This study demonstrates for the first time that the lymphatic progression of T1 human breast cancer is strongly related to apoptosis loss.     

Medical marijuana

To evaluate the use of high-resolution magnetic resonance imaging (MRI) for the differentiation of skin tumors in the maxillofacial region, 60 patients (25 female) were examined in a 1.5-T whole-body MR imager with a 2.5-cm surface coil. Plain transverse T1-(TR 500 ms, TE 25 ms), T2-(2200 ms, TE 80 ms), fat-(TR 500 ms, TE 28 ms), and water-suppressed (TR 500 ms, TE 38 ms) SE sequences were used. Following the application of the paramagnetic contrast agent Gd-DTPA, transverse T-weighted and fat suppression sequences were repeated. Before and after contrast administration, tumor signal intensities and percent contrast enhancement were determined by a ROI technique. All tumors were classified by standard histologic technique and evaluated with regard to their response to contrast medium. Quantitative evaluation was performed by three independent radiologists. Additionally, signal- and contrast-to-noise ratios were calculated for each tumor type. All MRI findings were compared with histology. Significant contrast enhancement occurred in most tumors; malignant tumors displayed inhomogeneous enhancement. The optimal pulse sequences for tumor delineation are plain T1-weighted, water-suppressed, and contrast-enhanced fat-suppressed sequences. Tumors could not be specified by signal intensities or percent contrast enhancement, and CNR did not allow for malignant lesions to be differentiated from benign tumors. High-resolution MRI proved to be an adequate method for imaging skin tumors and their inner structure. Tumor typing was not possible by either contrast-administration or modification of sequence parameters. In this regard, further innovations in contrast agent design seem to be necessary.     

Direct and indirect effects of chronic physical conditions on depression: a preliminary investigation

We have previously demonstrated that interleukin-2 (IL-2) receptors, IL-2 protein, and mRNA for IL-2 are present in human carcinomas in vitro and in vivo. Carcinoma cells synchronized in the G2/M-phase of the cell cycle express significantly more intracytoplasmic IL-2 as well as IL-2R-beta and -gamma than tumor cells in the G0/G1-phase. Here we evaluated immunohistologically the cell cycle-dependent distribution of the proliferation-associated Ki-67 antigen and expression of the cytokine IL-2 in four different carcinoma cell lines. In addition, 34 tissue samples from patients with squamous cell carcinomas of the head and neck were simultaneously analyzed for Ki-67 and IL-2 expression and the data were correlated to the histological grade of the tumors. All tumor cell lines were shown to express IL-2 in the Golgi complex. The strongest IL-2 expression was seen in tumor cells undergoing mitosis, identified by double staining with the antibody to Ki-67. In the tumor tissue, the highest level of co-expression of IL-2 and Ki-67 was observed in poorly differentiated carcinomas, with a labeling index (LI) of 67. 2% for IL-2 and 68.8% for Ki-67. Well-differentiated carcinomas showed a significantly lower expression of both proteins (LI 35.0% for IL-2 and 26.5% for Ki-67). The correlation between the labeling indices was statistically significant (r = 0.747; p<0.001). These results demonstrate that IL-2 expression in human carcinoma tissues is strongly associated with cell proliferation and significantly correlates with the histological tumor grade.     

Expression of nm23 in gastric carcinoma: association with tumor progression and poor prognosis

BACKGROUND: Expression of nm23 has been shown to be inversely correlated with the metastatic potential of several human cancers. In the current study, the expression and prognostic impact of nm23 was immunohistochemically studied in 413 curatively resected gastric carcinomas. METHODS: Tumor sections of the 413 gastric carcinomas were stained with a polyclonal antibody that was raised against the nm23-H1/NDP kinase A, which is identical to the nm23-H1 gene product. RESULTS: Expression of nm23 was detected in 84.5% (n = 349) of all tumors, in the majority of cases (71.2%) causing a homogeneous staining reaction in more than 75% of tumor cells. Expression of nm23 was positively correlated with the intestinal type of tumor, according to the Lauren classification and advanced pT categories, and was also correlated with the presence of blood and lymphatic vessel invasion. In contrast, no correlation could be demonstrated between nm23 expression and lymph node involvement. As shown in univariate analysis, patients with nm23 positive tumors, especially those with nm23 positive diffuse-type carcinomas, had significantly shorter overall survival than patients with nm23 negative tumors (P = 0.03 and P = 0.0065, respectively). However, in a multivariate analysis that included the prognostic parameters pT category, pN category, and blood and lymphatic vessel invasion, this prognostic impact was not maintained. CONCLUSIONS: In contrast to results for breast and colorectal carcinomas, our results for 413 gastric carcinomas showed that expression of the designated metastasis suppressor gene nm23 is correlated with aggressive tumor growth and poor prognosis but is not an independent prognostic marker.     

Evaluation of the antibody response in pigs vaccinated against Streptococcus suis capsular type 2 using a double-antibody sandwich enzyme-linked immunosorbent assay

OBJECTIVE: We assessed the value of dynamic sequential three-dimensional Fourier transformation (3DFT) MRI in differentiating various types of small liver tumors. MATERIALS AND METHODS: Forty-seven patients with 65 liver masses < 3 cm in size (42 hepatocellular carcinomas, 11 hemangiomas, 12 metastatic tumors) were studied by 3DFT fast imaging with steady-state precession (FISP) MRI [TR(ms)/TE(ms)/flip angle (degree): 20/8/30]. The slab thickness was 21-35 mm, and there were seven partitions. The 3DFT-FISP MR images were obtained immediately after 0.1 mmol/kg of gadopentetate dimeglumine was administered intravenously over 2-3 s (early phase), 60 s after (late phase I), and 120 s after (late phase II). RESULTS: Eighty-six percent of small hepatocellular carcinomas showed hyperintense enhancement relative to the surrounding liver parenchyma and iso- or hypointense enhancement with or without capsular enhancement in the late phase. Eighty-two percent of small hemangiomas showed peripheral globular enhancement in the early phase and total hyperintense or peripheral enhancement in the late phases. Ninety-two percent of the small metastatic liver tumors showed doughnut-like ring enhancement in the early phase. CONCLUSION: By dynamic 3DFT-FISP MRI, we were able to accurately evaluate the hemodynamics and morphological findings of each type of small liver tumor.     

VCAM (IGSF) adhesion molecule expression in breast carcinomas detected by automated and quantitative immunocytochemical assays

Expression of vascular cell adhesion molecules (VCAM) in tumors is associated with endothelial cell activation and may facilitate adherence of carcinomatous cells to the vessel wall, promoting bloodborne metastases. Expression of VCAM was investigated in 202 breast carcinomas using automated (Ventana System) and quantitative (SAMBA image analyzer) immunoperoxidase staining of frozen sections. Positive VCAM immunoreactivity was observed in 83 tumors (41%) (mean immunostained surface, 12.4%; SD, 10.5). The mean area of immunostaining was correlated with clinical and pathologic prognostic indicators and with the immunohistochemical expression in tissue sections of various indicators of cell proliferation, metastatic potential, and drug resistance or sensitivity, evaluated according to the same method. There was no correlation of VCAM immunoreactivity with tumor size, type, or grade or with nodal status. Also, no significant correlation was observed between VCAM and MIB1/Ki67, p53, Bcl-2, E cadherin, CD44v, cathepsin D, CD31, P-gp, ER, PR, or pS2. However, VCAM immunoreactivity was significantly correlated with ELAM and VLA2 (P = .001) and VLAs (P = .008) expression. The results suggest that VCAM expression in breast carcinoma tissue sections is likely not a prognostic indicator. Its practical clinical relevance, if any, must be established by correlation with patients' outcomes and tumor sensitivity to drugs.     

Prognostic value of nuclear grade of renal cell carcinoma

BACKGROUND: The authors assessed the interest and the value of Fuhrman's nuclear grade as a possible prognostic factor for renal cell carcinoma (RCC). METHODS: An 11-year retrospective study of 190 patients with RCC treated by radical nephrectomy was performed. The distribution by grade was: Grade I, 54 patients; Grade II, 58; Grade III, 58; and Grade IV, 20. The distribution of the patients by tumor stage according to the TNM15 classification was: pT1, 56 patients; pT2, 41; pT3a, 55; pT3b, 25; pT3c + pT3d + pT4b, 5; and pT4a, 8. Significant correlations with other prognostic parameters were noted. Survival curves by grade were evaluated by the Kaplan-Meier method. RESULTS: Nuclear grade was correlated with tumor stage (P = 0.0001), synchronous metastases (P = 0.003), lymph node involvement (P = 0.0001), renal vein involvement (P = 0.0001), tumor size (P = 0.0001), and perirenal fat involvement (P = 0.001). No correlation was found between nuclear grade and tumor multicentricity (P = 0.14) and cell type (P = 0.2). Nuclear grade was an effective parameter in predicting development of distant metastases after nephrectomy. Among the 54 patients who presented with Grade I tumors, only one tumor did metastasize during the 5-year follow-up, whereas 17% of the Grade III and 30% of the Grade IV tumors metastasized. The 5-year actuarial survival rates of the patients with Grade I, II, III, and IV tumors was 76%, 72%, 51%, and 35%, respectively. The comparison of the survival curves by grade showed a statistically significant difference between the curves when Grade I and II tumors were compared with Grade III and IV tumors (P = 0.001). CONCLUSION: In this study, nuclear grade was found to have prognostic significance and seems to be an important criterion when considering the outcome of patients with RCC.     

Fragile-X: neuropsychological test performance, CGG triplet repeat lengths, and hippocampal volumes

The purpose of this study was to compare a new MR macromolecular contrast medium (MMCM), gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-24-cascade-polymer, to a well-studied prototype MMCM, for the potential of distinguishing tissues of varying endothelial permeability. Three tissue models of varying capillary permeability were studied in a total of 46 rats: normal myocardium (normal capillaries), subcutaneously implanted adenocarcinoma (mild capillary leak), and reperfused infarcted myocardium (high capillary leak). TI-weighted MRI was performed before and dynamically after injection of either albumin-(Gd-DTPA)30 or the cascade polymer (each .02 mmol gadolinium [Gd] per kg). Data analysis based on a two-compartment kinetic model yielded estimates of fractional blood volume (BV) (percentage) and fractional leak rate (FLR) (1 per hour). Permeability to the cascade polymer as reflected in FLR was considerable in normal myocardium (8.24 per hour), of similar value in tumors (8.55 per hour), but significantly greater in infarcted myocardium (39.17 per hour, P < .01) versus normal myocardium. The larger albumin-(Gd-DTPA)30 demonstrated minimal extravasation in normal myocardium (FLR .33 per hour); FLR in tumors was 100% higher (.66 per hour, P < .002) and FLR in reperfused capillaries was significantly greater (7.94 per hour, P < .001). Based on capillary permeability measurements, the cascade polymer may have limited utility for detection of mildly increased microvascular permeabilities. For severe tissue injury, the cascade polymer can resolve abnormal microvascular integrity.     

Apoptotic index in ovarian carcinoma: correlation with clinicopathologic factors and prognosis

The apoptotic index (apoptotic cells/1000 tumor cells, AI) was evaluated in 71 ovarian carcinomas, all surgically resected. Apoptosis was examined by modified terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) method in histologic sections. High AI (>/=2.8) significantly correlated with high mitotic index (P = 0.05), high histologic grade of the tumor (P = 0. 018), and short overall survival (P = 0.017). An inverse relationship between AI and bcl-2 protein expression was also observed (P = 0.007). In addition, AI was assessed in 5 ovarian epithelial tumors of borderline malignancy, and all were categorized as low AI (<2.8). No significant correlation was found between AI and other clinicopathologic factors, such as age, clinical stage, lymph node metastasis, tumor size, histology of the tumor, and expression of p53 protein. Multivariate survival analysis showed that only clinical stage (P = 0.0395) and mitotic index (P = 0.0387) had independent prognostic value, whereas AI did not. Our results suggest that counting apoptosis can be useful for predicting the patient survival in ovarian carcinoma, although AI is not an independent prognostic factor. It is also suggested that bcl-2 protein is an important regulator of apoptosis in ovarian carcinoma.     

Immunohistochemical analysis of metallothionein in astrocytic tumors in relation to tumor grade, proliferative potential, and survival

BACKGROUND: Metallothionein (MT) is the name for a family of predominantly intracellular protein thiol compounds involved in anticancer drug resistance. For certain tumors, MT is related to grade of tumor malignancy and prognosis. The authors evaluated the expression of MT in 114 astrocytic tumors in relation to the proliferative potential of tumors and the survival of patients. METHODS: Paraffin embedded tissue sections were stained with monoclonal anti-metallothionein and MIB-1 Ki-67 antibodies by avidin-biotin complex immunohistochemistry. RESULTS: MT expression was observed in 2 of 6 pilocytic astrocytomas, in 10 of 24 Grade 2 astrocytomas, in 16 of 25 anaplastic astrocytomas, and in 47 of 59 glioblastomas. In addition to the tumor cells, microvascular endothelial proliferation and smooth muscle of tumor vessel walls were frequently MT positive. The glioblastomas had a significantly higher percentage of MT positive cells compared with low grade (P < 0.0001) and anaplastic (P < 0.04) astrocytomas. MT expression in astrocytomas had no correlation with tumor recurrence. The mean Ki-67 labeling index (LI) was significantly higher in the high grade (3-4) compared with the low grade (1-2) astrocytomas. MT positive astrocytic tumors had statistically significantly higher mean Ki-67 LI compared with MT negative tumors, irrespective of histologic grade. Although the levels of MT and Ki-67 LI varied in individual tumors, the mean Ki-67 LI increased in parallel to the increasing MT staining grade, and this difference attained statistical significance only for glioblastoma. MT positive anaplastic astrocytoma and glioblastoma patients did not survive as long as the MT negative patients, although this difference attained statistical significance only for anaplastic astrocytoma. CONCLUSIONS: The current study suggests that MT might play a significant role in the growth of astrocytic tumors, with an acquired enhanced ability to produce MT as the malignant potential of a tumor increases.     

19F-MR imaging of transplanted tumor: perfluorochemicals as a fluorine tumor imaging agent

PURPOSE: The purpose of our study was to detect tumor selectively using 19F-magnetic resonance imaging (MRI) and to assess Fluosol-DA, a perfluorochemical emulsion, as a tumor imaging agent for 19F-MRI. MATERIALS AND METHODS: SCC VII cells were transplanted in the right leg of mice. After 6 days, Fluosol-DA was administrated intravenously (40 ml/kg). 19F-MR imaging was performed on a Bruker CSI Omega 2 at 4.7 Tesla using a homemade volume coil. RESULTS: In vitro, the concentration and 19F signal intensity of FDA showed a very high correlation (r = 0.9997). Detection on MRI was possible at a concentration of 2%. In vivo, images of 19F in SCC VII tumors were achieved in animals 2 days after the administration of FDA. CONCLUSION: Our study confirms the feasibility of 19F-MR in vivo imaging of tumors using the fluorine compound FDA.