Characteristics Of Tumor Tissue Research Articles

Shear wave induced resonance elastography of spherical masses with polarized torsional waves

Shear Wave Induced Resonance (SWIR) is a technique for dynamic ultrasound elastography of confined mechanical inclusions. It was developed for breast tumor imaging and tissue characterization. This method relies on the polarization of torsional shear waves modeled with the Helmholtz equation in spherical coordinates. To validate modeling, an in vitro set-up was used to measure and image the first three eigenfrequencies and eigenmodes of a soft sphere. A preliminary in vivo SWIR measurement on a breast fibroadenoma is also reported. Results revealed the potential of SWIR elastography to detect and mechanically characterize breast lesions for early cancer detection.

A male infant presenting with acute urinary retention

A 3-month-old male infant was admitted to the emergency department for acute urinary retention. A voiding cystourethrogram was performed because urethral valves were suspected. After bladder catheterization, the plain radio - graph prior to filling of the bladder showed an abnormal course of the urinary catheter tip together with focal absence and displacement of bowel gas out of the pelvis. Early contrast opacification of the bladder (Fig. A) demonstrated an abnormal cranial position of the lumen and an extrinsic impression on the bladder base, which became obscured after further distension of the bladder (Fig. B). These findings suggested presence of a pelvic mass, which was confirmed sonographically. CT and MRI were performed for better tumor delineation and tissue characterization. Both demonstrated a sharply delineated presacral soft tissue mass with homogeneous enhancement and DWI showed diffusion restriction. Sagittal T2-weighted image (Fig. C) nicely exhibits upward elevation of the bladder caused by a homogeneous presacral mass. Serum analysis showed increased neuron specific enolase and increased catecholamine metabolites were found in the urine. Tru-cut biopsy specimens confirmed neuroblastoma. CT and MIBG scan revealed no distant sites outside the pelvis while a bone scinti - graphy ruled out bone metastases. The tumor was macroscopically completely removed by means of a median laparotomy, and the infant recovered well after therapy.

Frequency-Domain Analysis of Photoacoustic Imaging Data From Prostate Adenocarcinoma Tumors in a Murine Model

Photoacoustic imaging is an emerging technique for anatomical and functional sub-surface imaging but previous studies have predominantly focused on time-domain analysis. In this study, frequency-domain analysis of the radio-frequency signals from photoacoustic imaging was performed to generate quantitative parameters for tissue characterization. To account for the response of the imaging system, the photoacoustic spectra were calibrated by dividing the photoacoustic spectra (radio-frequency ultrasound spectra resulting from laser excitation) from tissue by the photoacoustic spectrum of a point absorber excited under the same conditions. The resulting quasi-linear photoacoustic spectra were fit by linear regression and midband fit, slope and intercept were computed from the best-fit line. These photoacoustic spectral parameters were compared between the region-of-interests (ROIs) representing prostate adenocarcinoma tumors and adjacent normal flank tissue in a murine model. The mean midband fit and intercept in the ROIs showed significant differences between cancerous and noncancerous regions. These initial results suggest that such frequency-domain analysis can provide a quantitative method for tumor tissue characterization using photoacoustic imaging in vivo. (E-mail: cxdeng@umich.edu and xdwang@umich.edu)

Abstract 2684: Telomere length of carcinoma-associated fibroblasts as a biomarker for breast cancer local recurrence

Abstract The use of breast-conservative surgery (BCS) for the treatment of early-stage breast cancers has been increasing and the ability to identify patients at high risk of local recurrence is highly desirable for guiding treatment decisions. Currently, relatively few breast cancer local recurrent risk factors have been identified; those known risk factors, which are based on clinical and histological features of tumor tissue, have limited predictive power. It is known that molecular genetic changes often precede morphologic evidence of malignant transformation. Thus, early molecular genetic alterations in breast tumor and adjacent normal tissues are likely to be more sensitive tools for the identification of patients at increased risk of local recurrence than current histological criteria. A nested case-control study was carried out to evaluate whether telomere length in morphologically normal tissues adjacent to the tumor is predictive of breast cancer local recurrence. One hundred forty-two women who are diagnosed with breast cancer at Lombardi Comprehensive Cancer Center between 1998 and 2005 were included in the study. Cases (N = 42) are patients who had local recurrences of breast cancer after BCS. Controls (N = 100) are patient who had no local recurrence and are matched to cases on year of surgery, age at diagnosis, disease stage and type of surgery. Quantitative telomere fluorescent in situ hybridization (FISH) was used to determine the telomere length of four cell types: cancer cells, carcinoma-associated fibroblast cells (CAFs), adjacent normal epithelial cells and lymphocytes, using 5-micron sections of formalin fixed paraffin-embedded (FFPE) breast tumor tissues. Telomere length of lymphocytes was used to normalize the FISH hybridization variation and relative telomere length (RTL) was defined as telomere length in cells of interest divided by the telomere length of lymphocytes. Multivariate logistic regression was used to assess the association between RTL and breast cancer local recurrence. We found that mean RTL of CAFs was significantly longer in patients with breast cancer local recurrence (mean = 0.99) than in patients without local recurrence (mean = 0.74, p=0.022). When RTL of CAFs were dichotomized using median value of control subjects, patients who had longer RTL in CAFs had 2.4-fold (95% CI=0.86-6.56) increased risk of breast cancer local recurrence than women who had shorter RTL in CAFs. We observed no statistically significant case-control difference in mean RTL of normal epithelial cells adjacent to the tumor (p = 0.712) or in mean RTL of cancer cells (p = 0.285). This study is the first to report that telomere length in tumor stromal cells (CAFs) is associated with breast cancer local recurrence. If confirmed by future studies, telomere length in CAFs has the potential to become a novel molecular tool for the predicting breast cancer local recurrence. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2684.

IDQC anisotropy map imaging for tumor tissue characterization in vivo

Intermolecular double quantum coherences (iDQCs), signals that result from simultaneous transitions of two or more separated spins, are known to produce images that are highly sensitive to subvoxel structure, particularly local anisotropy. Here we demonstrate how iDQCs signal can be used to efficiently detect the anisotropy created in breast tumor tissues and prostate tumor tissues by targeted (LHRH-conjugated) superparamagnetic nanoparticles (SPIONs), thereby distinguishing the necrotic area from the surrounding tumor tissue.

Possible changes in the genomic features of tumor tissues over the last 150 years

Possible changes in the genomic features of tumor tissues over the last 150 years

IDQC anisotropy map imaging for tumor tissue characterization in vivo

IDQC anisotropy map imaging for tumor tissue characterization in vivo

Tumor tissue characterization evaluating the luciferase activity under the control of a hsp70 promoter and MR imaging in three tumor cell lines

We investigated the luciferase activity under the control of a hsp70 promoter and MR imaging for three tumor cell lines. Three tumor cell lines, SCCVII, NIH3T3 and M21 were transfected with a plasmid containing the hsp70 promoter fragment and the luciferase reporter gene and grown in mice. Bioluminescence imaging of the tumors was performed every other day. MR imaging, pre- and post-contrast T1-wt SE, T2-wt FSE, Diffusion-wt STEAM-sequence, T2-time determination were obtained on a 1.5-T GE MRI scanner at a tumor size of 600–800 mm 3 and 1400–1600 mm 3. Comparing the different tumor sizes the luciferase activity of the M21 tumors increased about 149.3%, for the NIH3T3 tumors about 47.4% and for the SCCVII tumors about 155.8%. Luciferase activity of the M21 tumors ( r = 0.82, p < 0.01) and the SCCVII tumors ( r = 0.62, p = 0.03) correlated significant with the diffusion coefficient. In the NIH3T3 tumors the best correlation between the luciferase activity and the MRI parameter was seen for the SNR (T2) values ( r = 0.78, p < 0.01). The luciferase activity per mm 3 tumor tissue correlated moderate with the contrast medium uptake ( r = 0.55, p = 0.01) in the M21 tumors. In the NIH3T3 and SCCVII tumors a negative correlation ( r = −0.78, p < 0.01, respectively, r = −0.49, p = 0.02) was found with the T2 time. Different tissue types have different luciferase activity under the control of the same hsp70 promoter. The combination of MR imaging with bioluminescence imaging improves the characterization of tumor tissue giving better information of this tissue on the molecular level.

Functional diagnosis of residual lymphomas after radiochemotherapy with positron emission tomography comparing FDG- and FLT-PET

Positron emission tomography (PET) using 2-deoxy-2-[18F]fluoro-d-glucose (FDG) is used as a functional imaging technique for the staging and follow-up of lymphomas. However, additional information about the tumor proliferation rate using 3′-deoxy-3′-[18F]fluorothymidine (FLT) may be useful for the assessment of prognosis. We enrolled 48 patients with Hodgkin's (n = 15) and non-Hodgkin's lymphoma (n = 33) with residual masses >2 cm examined by tracer studies with FDG and FLT. The results were related to median overall and progression-free survival. In 15 out of 48 patients analysed using FDG, positive results were found. Using FLT, 10 out of 48 patients were positive. 33 patients were FDG negative. Eight patients were positive both using FDG and FLT. Overall survival for patients with a negative PET scan was significantly higher than for patients with positive PET, irrespective of the tracer used. FLT alone was able to discriminate between patients with long or short overall survival. However, there was no statistical significance comparing FDG/FLT negative versus FDG negative alone. Although FDG detected more lesions than did FLT, the additional biological characterization of tumor tissue with respect to proliferation by FLT might be useful by providing complementary information for the identification of recurrence. However, the present data show no advantage of combined FDG/FLT studies over FDG alone with respect to the prediction of survival.

CCPM Symposium II - 01: Imaging breast tumor tissue in vivo with diffuse light: Tumor tissue characterization and monitoring

Diffuse optical tomography with near-infrared light has allowed characterization of breast tumor tissue with a number of different constituent parameters, which could have relevance for diagnosis and therapy. Multi-spectral tomography provides quantification of hemoglobin, oxygen saturation, water, and scatterer particle size and density. These parameters are shown for normal and diseased breast tissue, with an eye toward their pathobiological interpretation. The images of tumors present in breast cancer show significant increases in hemoglobin, water and scattering relative to the corresponding normal tissue, and the results of ongoing clinical trials are presented. The scattering particle size is shown to be correlated to the pathologically measured particle sizes in excised breast tissue, and further model-based interpretation of the scatter signal may yield important structural information at the nanometer level in tissue, as measured macroscopically with NIR tomography. Imaging of fluorescence from tissue is also possible and is presented, along with a demonstration of how the technological design can be altered to allow video-rate imaging similar to an ultrasound scanner.

CALGB 9840: Phase III study of weekly (W) paclitaxel (P) via 1-hour(h) infusion versus standard (S) 3h infusion every third week in the treatment of metastatic breast cancer (MBC), with trastuzumab (T) for HER2 positive MBC and randomized for T in HER2 normal MBC

512 Background: W P is active, well tolerated and feasible with high efficacy alone or with T (Seidman et al. JCO 1998 and 2001). The primary aims of this trial were to determine whether: 1) W P improves response rate (RR) vs. S P, regardless of HER2 status and assignment to T, and 2) T added to P improves RR vs. P alone for HER2 normal tumors. Secondary objectives were to evaluate time to progression (TTP) and overall survival (OS) with respect to the above comparisons. Methods: Patients (pts) with measurable MBC, 0–1 prior chemotherapy regimens for locally advanced or MBC, ≥ 1 year from adjuvant taxane (if any) were stratified by line of therapy and randomized unequally (40:60) to S P 175 mg/m2 or W P 80 mg/m2. After accrual of the first 171 pts, when T became accepted as standard therapy for pts with HER2 positive MBC (Slamon et al NEJM 2001), HER2 status was assessed locally, pts with HER2 positive MBC received T and pts with HER2 normal MBC were randomized for T (standard weekly dosing). 158 pts treated with S P in the prior CALGB 9342 trial (Winer et al. JCO 2004) contributed data to the S P group in C9840 by pre-designed analyses. Results: 585 pts entered (488 first-line/97 second-line), and 577 were treated (n=735 with C9342 pts). Efficacy was analyzed as prescribed in adjusted multivariate models, controlling for relevant covariates including line of therapy and trastuzumab use. W P was superior to S P with respect to RR: 40% vs. 28%, (OR=1.61, p=0.017), and TTP: 9 vs. 5 mos, (HR=1.45, p = 0.0008). In this model, OS was 24 mos for W P vs. 16 mos for S P, (HR=1.19, p = 0.17). For pts with HER2 normal MBC, T did not improve RR: 35% vs. 29%, p=0.34, TTP: 7 vs. 6 mos, p=0.09, or OS: 22 vs. 20 mos, p=0.67. W P caused more grade 3 sensory/motor neuropathy (23/8% vs. 12/4%, p=0.001/0.04), and less grade ≥ 3 granulocytopenia (8 vs. 15%, p=0.013). 5 pts (0.8%) experienced significant cardiac dysfunction, 4 on T arms. There were 2 treatment related deaths, both due to pneumonia, on W P. Conclusions: W P is superior to S P in the management of MBC. T does not improve efficacy of P in HER2 normal MBC. Characterization of tumor tissue for HER2 (immunohistochemistry and fluorescent in situ hybridization) and other potential correlates of T sensitivity is ongoing centrally, as are analyses of serial changes in serum HER2 extracellular domain and quality of life. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb

Loss of Antigenicity in Stored Sections of Breast Cancer Tissue Microarrays

Abstract Immunohistochemical characterization of tumor tissues in epidemiological studies is a promising approach to identify breast cancer subtypes with distinct etiology. The recent development of the tissue microarray (TMA) technique allows for standardized, rapid, and cost-effective immunohistochemical characterization of many cases, which is critical in epidemiological studies. Sectioning paraffin blocks at different times results in loss of material, which can be reduced by preparing many sections each time a block is cut. However, data suggest that staining intensity declines in whole sections prepared from conventional paraffin blocks with storage time, resulting in false-negative results. This problem would be accentuated in TMAs because of the limited tissue representation of each case. To evaluate this concern, we prepared a single TMA block from 125 invasive breast carcinomas collected in a population-based case-control study conducted in Poland and compared estrogen receptor (ER-α), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression in sections cut and stored for 6 months at room temperature with sections cut from the same TMA block and stained on the same day. Percentage of positive cases for stored versus fresh sections was similar for ER (59.0%) but significantly higher in fresh sections for PR (56.3% versus 64.1%, P = 0.01) and HER2 (45.5% versus 64.4%, P &amp;lt; 0.001). Among cases positive in both stored and fresh sections, the median percentage of immunoreactive cells was significantly reduced and the staining intensity was consistently lower in stored compared with fresh sections. We conclude that loss of immunoreactivity is an important problem in TMAs of breast cancer. Improved methods for sectioning TMAs and storing tissue sections aimed at reducing loss of immunoreactivity are critical for the use of TMAs in epidemiological studies.

Proteomic characterization of the human cortical neuronal cell line HCN-2

Neuronal marker proteins are widely used for characterization and identification of normal and tumor tissue of the central nervous system, but the most commonly used neuronal markers have inherent methodological problems. We used a proteomic approach with two-dimensional (2-D) gel electrophoresis and subsequent MALDI identification to identify possible new marker proteins in the human cortical neuronal cell line HCN-2. We found 14 proteins that previously were predicted only on the basis of open reading frames from mRNA sequences or DNA. We could unambiguously identify the following proteins: Bab55091, BK65A6.2 (Novel Sushi Domain (Scr repeat), glucosidase II alpha subunit, glucosidase II precursor (KIAA0088 protein), HSPC108, hypothetical 35.8 kDa protein, hypothetical 40.7 KDA protein, hypothetical 49.4 kDa protein, leucine-zipper protein FKSG13, lysophospholipase homolog, mitofilin (fragment), P1.11659_4, reticulocabin precursor and one unknown protein for MGC:10432. We could prove the existence of these 14 proteins in the human neuron, extending the list of proteins with neuronal expression and identify possible new candidate marker proteins.

Laser-based spectroscopic methods in tissue characterization.

Laser-based spectroscopic techniques were developed for tumor tissue characterization utilizing different tumor-localizing substances. In particular, sensitization with the heme precursor delta-amino levulinic acid (ALA) administered topically, orally or intravenously was used for the induction of protoporphyrin IX (PpIX). The autofluorescence as well as the PpIX-related fluorescence signals were monitored, and tumor demarcation functions were calculated for different human malignant tumors, such as tumors in the urinary bladder and the prostatic gland, in the head and neck region, in the breast and in the gastrointestinal tract. In the gastrointestinal tract, colon tumors were examined as well as tumors and dysplastic lesions in the esophagus, where patients with Barrett's esophagus were examined. Time-integrated laser-induced fluorescence measurements utilizing a point monitoring fluorosensor and a multicolor fluorescence imaging system were performed in vivo in patients in different clinical specialities.

Dysprosium-enhanced MR imaging for tumor tissue characterization. An experimental study in a human xenograft model.

To evaluate dysprosium-enhanced MR imaging for differentiation between morphologically intact and necrotic tumor tissue in a tumor model. A human colon carcinoma was transplanted subcutaneously into 9 nude (immunodeprived) rats. MR imaging was performed before and after injection of the dysprosium agent Dy-DTPA-BMA. T1-, T2- and T2*-weighted sequences were acquired. The tumors were dissected, histological sections were prepared, and compared with corresponding MR images. In intact tissue, the MR signal intensity in the T2- and T2*-weighted images decreased after Dy injection and the delineation of the intact regions were sharp and corresponded well to the gross histological sections. Dy-enhanced MR imaging facilitated the differentiation between intact and necrotic tumor tissue.

Dysprosium-enhanced MR imaging for tumor tissue characterization

Dysprosium-enhanced MR imaging for tumor tissue characterization

Primary liver neoplasms: MR imaging with pathologic correlation.

Magnetic resonance (MR) imaging is a powerful tool in the evaluation of primary liver neoplasms. Determination of tumor extent and tissue characterization is provided with standard spin-echo T1- and T2-weighted imaging and is enhanced by the application of advanced sequences such as gradient-echo, fast spin-echo, and fat suppression techniques. Intravenously administered contrast agents, such as gadopentetate dimeglumine and superparamagnetic iron oxide, provide additional opportunities for lesion characterization. Knowledge of the underlying gross and microscopic pathologic features of primary hepatic neoplasms leads to a better understanding of their often complicated MR imaging appearances. The authors correlate the key pathologic features with the most significant MR imaging findings of primary benign and malignant liver neoplasms, including hemangioma, focal nodular hyperplasia, hepatocellular adenoma, infantile hemangioendothelioma, mesenchymal hamartoma, hepatocellular carcinoma, fibrolamellar carcinoma, intrahepatic cholangiocarcinoma, biliary cystadenoma and cystadenocarcinoma, angiosarcoma, hepatoblastoma, and undifferentiated embryonal sarcoma.

Alterations in lectin binding in the proximal and distal colon of Sprague-Dawley rats with 1,2 dimethylhydrazine administration

Sequential changes in rhodamine or fluorescein isothiocyanate-conjugated lectin binding of proximal and distal colonic crypts were studied during and after the administration of the 1,2 dimethylhydrazine (DMH). Five adult its unexposed to DMH or vehicle served as baseline controls. Tissue from normal appearing colon and tumor tissue was incubated with Ulex europaeus agglutinin 1 (UEA), Arachis hypogaea (PNA), Dolichos biflorus (DBA) and Griffonia simplicafolia 1 (GSA1). Distinct regional differences were noted in the baseline controls. UEA, PNA and DBA binding were absent in the distal colonic crypt cells. In the proximal colon minimal UEA and PNA binding was noted in the lower crypt whereas DBA binding was intense. GSA1 binding was diffuse in the upper and lower crypt of both regions. During carcinogenesis a progressive increase in PNA binding was noted in normal appearing colonic crypts from both regions. A progressive increase in PNA binding in proximal and distal colonic tumors was noted over time. Similar to normal tissue, DBA bound markedly to proximal colon tumors but was absent in most distal colonic tumors. UEA stained all proximal tumors intensely at all time points. In distal colonic tumors, UEA staining was diminished at 30 weeks compared to tumors analyzed at 16, 22 and 26 weeks. Mucin depletion was also a feature of tumor tissue compared to adjacent normal and hyperplastic glands. This study documents the region specific changes in lectin binding in normal and neoplastic colonic crypts induced by DMH.

Pulmonary metastases: Pathological anatomy

In most cases, the histopathological examination of pulmonary metastases will lead to vital clues indicating the primary tumor even after years of disease-free intervals. When evaluating 344 metastases of 100 patients, correlation to the known primary tumor was possible in 98% of the cases. Important additional information may be gained by regression grading of metastases, for example after chemotherapy. In 28 metastases of 4 patients suffering from primary tumors of the testicle, no vital tumor tissue could be demonstrated. The age peak of patients with surgically removed pulmonary metastases was between 40 and 50 years, varying widely, however, depending on the primary lesion. The size of the resected metastases was between 1 and 100 mm, with a peak of 6-10 mm. The examination of early metastases enhanced our knowledge concerning the different phases of metastatic spread such as embolization, implantation, metastatic growth with neoangiogenesis, spontaneous or therapeutically induced tumor regression and local reactions of the pulmonary tissue. The characterization of tumor tissue using, among others, immunohistochemical techniques will lead to clinical and therapeutic consequences.

Updating computed tomography of bladder carcinoma in assessing response to immunotherapy and attenuated irradiation

Computed tomography (CT) was utilized as part of the surgical-pathologicradiologic evaluation of 21 patients who were treated for bladder carcinoma with attenuated irradiation and immunotherapy. Fifteen patients had moderately infiltrative (Stage B 2-C or less) disease, and it was found that a routine high resolution CT technique using a modern fast scanner delineated the tumor in most cases. More accurate assessment of tumor response to therapy and evaluation of tumor progression were facilitated using a gas insufflation technique combined with intravenous contrast infusion. This was followed in selected cases by quantitative measurements of CT attenuation values using a recently introduced CT software program. Using this program, individual pixel values were obtained in selected areas and evaluation of the resulting numerical data and pixel histograms aided in the differentiation of tumor tissue from adjacent bladder wall and mapped out areas of tumor necrosis. Our preliminary observations suggest that quantitative CT studies incorporating assessment of printouts of attenuation values of adjacent pixels within a region of interest will improve the delineation of smaller (B1/B2) lesions and will aid objective characterization of tumor tissue during and following therapy.