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Results for “Tissue Array Analysis”

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PubMed2007

Prominent expression of metalloproteinases in early stages of ovarian tumorigenesis.

The role for matrix metalloproteinases (MMPs) in tumor cells invasion and metastasis is well established, and expression of MMPs is recognized as an indication of tumor cell malignancy. Previous studies suggest that the degradation of the basement membrane is a crucial early step in epithelial transformation and ovarian tumorigenesis. Thus, MMPs may also express and exert a role in preneoplastic lesions of ovarian tissues. We investigated the expression of the major metalloproteinases, gelatinase A, 72 kDa type IV collagenase (MMP-2), and gelatinase B, 92 kDa type IV collagenase (MMP-9), and the presence of basement membrane in ovarian tumors and tissues from prophylactic oophorectomies using immunostaining. MMP expression was also characterized in a panel of ovarian cancer cell lines and several nontumorigenic ovarian surface epithelial primary cells by zymography, Northern, and Western blots. We found, surprisingly, that MMP-2 and MMP-9 are expressed more frequently in early lesions than in established carcinomas. No correlation was found between the expression of MMPs and tumor grades or stages. In preneoplastic lesions, MMP-2 or MMP-9 expression often associates with the absence of basement membrane and morphological alterations. MMP-2 is often expressed in nontumorigenic ovarian surface epithelial cells but reduced or absent in cancer cells. Thus, we conclude that MMPs expression does not correlate with the malignancy of ovarian epithelial cells as generally thought. Rather, increased metalloproteinase expression is an early event in ovarian tumorigenesis and associates with the loss of epithelial basement membrane and morphological transformation. We propose that the increased MMP activity is an etiological factor for ovarian cancer risk. We found that MMPs expression does not correlate with the malignancy of ovarian epithelial cells as generally thought. Rather, increased metalloproteinase expression is an early event in ovarian tumorigenesis. The finding suggests roles of MMP in tumor initiation in addition to invasion, and may impact on the strategy for use of MMP inhibitors in cancer prevention.

Blotting, Northern↗

PubMed2004

Abnormalities in the NF-kappaB family and related proteins in endometrial carcinoma.

The NF-kappaB family of transcription factors regulates a wide variety of cellular processes including cell growth, differentiation, and apoptosis. A tissue microarray was constructed from paraffin wax-embedded blocks from 95 endometrial carcinomas (EC), previously studied for microsatellite instability, as well as for alterations in PTEN, k-RAS and beta-catenin. Immunohistochemical evaluation included members of the NF-kappaB (p50, p65, p52, c-Rel, Rel-B) and the IkappaB (IkappaBalpha, IkappaBbeta, IkappaBepsilon, Bcl-3) families, as well as putative targets of NF-kappaB such as Flip, Bcl-xL, Cyclin D1, and oestrogen and progesterone receptors. Results were correlated with the clinical and pathological data. Nuclear immunostaining for members of the NF-kappaB family was frequent in EC (p50, 20%; p65, 16.5-21.9%; p52, 9.3%; c-Rel, 48.9%; Rel-B, 15.7%); and it correlated with negativity for members of the IkappaB family in some cases. There was a statistically significant association between immunoreaction for p50 and p65 (p = 0.006), suggesting activation of the so-called 'classic form' of NF-kappaB, similar to that described in breast cancer. Bcl-3 nuclear immunostaining was detected in 60.7% of cases. The vast majority of p52-positive tumours showed Bcl-3 nuclear immunoreaction (p = 0.038). Immunostaining for putative targets of NF-kappaB was as follows: Bcl-xL, 76.2% (p = 0.001); Flip 43.0%; Cyclin D1, 64.79%. p65 immunostaining correlated with increased immunoreaction for steroid hormone receptors. No correlation was found between NF-kappaB nuclear pattern and the presence of microsatellite instability, or alterations in PTEN, k-RAS, or beta-catenin. These results suggest that the NF-kappaB and IkappaB families of genes may be important in endometrial carcinogenesis, by controlling apoptosis and cell proliferation.

Adenocarcinoma↗

PubMed2005

Macrophages direct tumour histology and clinical outcome in a colon cancer model.

Macrophages generally constitute a major component of the tumour stroma. Although conventionally considered to be cytotoxic effector cells, macrophages have recently been described as promoters of tumour progression. The present study shows that selective depletion of peritoneal or liver macrophages prior to CC531 tumour cell inoculation resulted in highly differentiated tumours in rats. In contrast, tumours from control rats, in which macrophages are abundantly present, showed a desmoplastic stromal reaction with hallmark features of malignancy, such as neovascularization and matrix remodelling, indicating that the presence of macrophages is associated with malignant histopathological differentiation. Remarkably, macrophage-depleted rats, bearing highly differentiated tumours, had a worse prognosis, as they displayed a higher tumour load and poorer survival. Thus, while macrophages direct tumours towards malignant tumour histology, their role in anti-tumour defence is important. The selective inhibition of macrophage functions involved in malignant progression without interfering with cytotoxic ability may therefore identify important new targets for cancer therapy.

Animals↗

PubMed2006

Increased expression of high mobility group A proteins in lung cancer.

High mobility group A (HMGA) proteins play an important role in the regulation of transcription, differentiation, and neoplastic transformation. In this work, the expression of HMGA 1 and 2 in 152 lung carcinomas of mainly non-small-cell histological type has been studied by immunohistochemistry in order to evaluate their feasibility as lung cancer markers. In 17 lung cancer cases, the related bronchial epithelial changes were also studied for HMGA1 and 2 expression. RNA expression of HMGA1a and b isoforms and of HMGA2 was determined by real-time semi-quantitative RT-PCR in 23 lung carcinomas. High expression of HMGA1 and HMGA2 at both mRNA and protein levels was detected in lung carcinomas, compared with normal lung tissue. Nuclear immunostaining for HMGA1 and 2 proteins also occurred in hyperplastic, metaplastic, and dysplastic bronchial epithelium. Increased nuclear expression of HMGA1 and 2 correlated with poor survival (for adenocarcinomas, HMGA1, p=0.006; HMGA2, p=0.05). While the expression of HMGA2 was significantly associated with cell proliferation (p=0.008), HMGA1 expression did not show any association with proliferation or apoptotic index. Sequencing of HMGA2 transcripts from tumours with very high expression showed a normal full-length transcript. As HMGA proteins were expressed in about 90% of lung carcinomas and their expression was inversely associated with survival, they may provide useful markers for lung cancer diagnosis and prognosis.

Aged↗

PubMed2006

Identification of transmembrane proteins as potential prognostic markers and therapeutic targets in breast cancer by a screen for signal sequence encoding transcripts.

This study demonstrates, through a combination of stringent screening methods and thorough validation, that it is possible to identify transmembrane proteins preferentially expressed in primary breast tumour cells. mRNA was extracted from tumour cells isolated from invasive breast cancers and it was then subtracted against normal breast tissue mRNA prior to the generation of a signal sequence-trap library. Screening of the library identified 31 positive clones encoding 12 cell-surface and 12 secreted proteins. The expression of a subset of transmembrane genes was then interrogated using a high-throughput method (tissue microarray) coupled with cutting-edge in situ techniques in a large cohort of patients who had undergone uniform adjuvant chemotherapy. Expression of CD98 heavy chain (CD98HC) and low-level expression of the insulin-like growth factor 2 receptor/mannose-6-phosphate receptor (IGF2R/M6PR) correlated with poor patient prognosis in the whole cohort. Expression of bradykinin receptor B1 (BDKRB1) and testis enhanced gene transcript (TEGT) correlated with good prognosis in woman with oestrogen receptor (ER)-negative breast tumours. These results indicate that this combined approach of isolating primary tumour cells, generating a library to specifically isolate signal-sequence-containing transcripts, and in situ hybridization on tissue microarrays successfully identified novel prognostic markers (BDKRB1, CD98hc, and TEGT) and potential transmembrane therapeutic targets (CD98hc) in breast cancer.

Apoptosis Regulatory Proteins↗

PubMed2007

BCAR1 expression in prostate cancer: association with 16q23 LOH status, tumor progression and EGFR/KAI1 staining.

BACKGROUND: The 16q23 locus has been recently suggested in both breast and prostate cancer to contain a gene involved in disease progression. The breast cancer antiestrogen resistance 1 (BCAR1) gene, located at 16q23, contributes to many cellular processes including migration and survival, and interacts in vitro with the growth factor receptor EGFR and the metastasis suppressor KAI1. METHODS: BCAR1, EGFR, and KAI1 expression was studied by immunohistochemistry on a tissue microarray containing 100 localized prostate cancers (LPC), 15 hormone refractory prostate cancers (HRPC), and 15 lymph node metastasis (LNM). Forty eight of the LPC were also analyzed for 16q23 LOH status using microsatellite markers. RESULTS: BCAR1 staining was present in 25% of LPC, associated with higher Gleason score, and in 60% and 80% of, respectively, LNM and HRPC. BCAR1 expression was inversely correlated with 16q23 LOH status (P < 0.001), and was associated with high EGFR staining (P < 0.02), and negative KAI1 expression (P < 0.01). CONCLUSIONS: BCAR1 expression in LPC seems to be regulated at least in part by genetic events. The increased expression of BCAR1 with disease progression suggests a potential interest for both prognosis and treatment.

Aged↗

PubMed2005

Immunohistochemical expression of p63, p53 and MIB-1 in urinary bladder carcinoma. A tissue microarray study of 158 cases.

P63 is a member of the p53 family, which plays a role in the differentiation of urothelium and is supposed to play a role in urothelial carcinogenesis. P53 and MIB-1 are recognised in many studies as predictive markers of progression, but few studies in the literature have examined p63. The aims of our study were to explore the expression of p63 in bladder carcinomas and to compare this expression to p53 and MIB-1, as well as to stage and grade. Tissue microarrays were performed on 158 urothelial carcinomas (56 pTa, 45 pT1 and 57>or=pT2). Immunohistochemical studies were performed with p63, p53 and MIB-1 antibodies. In our study we observed that p63 immunostaining is present in all cell layers in papillary urothelial neoplasm of low malignant potential (PUNLMP), but partially lost in non-invasive papillary urothelial carcinoma low grade (NILGC) and in pT1/>or=pT2 bladder cancers. P53 and MIB-1 displayed lower expression in PUNLMP/NILGC vs non-invasive papillary urothelial carcinoma high grade (NIHGC)/pT1, but there was no correlation between the expression of p63, p53 and MIB-1. Our study demonstrates that p63 expression distinguishes between PUNLMP/NILGC and NIHGC/pT1 (p=4.10(5)). A statistical difference disserving pTa and pT1/>or=pT2 with a statistical significance (p<10(-6)) could also be observed. P63 should be considered as an additional biomarker that might help pathologists to classify their patients.

Adult↗

PubMed2006

Podoplanin is expressed in subsets of tumors of the central nervous system.

Immunohistochemical analyses with the monoclonal antibody D2-40 were performed to ascertain the expression of podoplanin (a.k.a. T1-alpha, gp36, or aggrus) in tumors of the central nervous system (CNS) and to determine the diagnostic utility of the antibody. The analyses were performed on 325 tumors of various histologic types. The chief finding was almost constant immunoreactivity in ependymal tumors (37/40, 92.5%), choroid plexus papillomas (8/8, 100%), and meningiomas (100/100, 100%). The reactivity was considered "tissue-specific," as the corresponding normal tissue of each tumor was also found to express podoplanin. In addition, expression, not committed to the lineages, was found in many other tumor types, including astrocytic tumors, medulloblastomas, and hemangioblastomas, with variable frequency and intensity. The way of expression was not fully understood, but the expression in astrocytic tumors seemed to be associated with pronounced fibrous properties or malignant phenotype, as was shown by high-frequent expression in pilocytic astrocytomas (12/12, 100%) and glioblastomas (29/35, 82.9%). The present study has shown that podoplanin is expressed in several types of CNS tumors with variable frequency and intensity. Given the widespread expression of podoplanin, the antibody D2-40 is of little use in diagnostic practice for CNS tumors.

Animals↗

PubMed2006

Assessment of epidermal growth factor receptor (EGFR) expression in primary colorectal carcinomas and their related metastases on tissue sections and tissue microarray.

Metastatic colorectal carcinomas (CRC) resistant to chemotherapy may benefit from targeting monoclonal therapy cetuximab when they express the epidermal growth factor receptor (EGFR). Because of its clinical implications, we studied EGFR expression by immunohistochemistry on tissue sections of primary CRC (n=32) and their related metastases (n=53). A tissue microarray (TMA) was generated from the same paraffin blocks to determine whether this technique could be used for EGFR screening in CRC. On tissue sections, 84% of the primary CRC and 94% of the metastases were EGFR-positive. When matched, they showed a concordant EGFR-positive status in 78% of the cases. Moreover, staining intensity and extent of EGFR-positive cells in the primary CRC correlated with those observed in the synchronous metastases. On TMA, 65% of the primary CRC, 66% of the metastases, and 43% of the matched primary CRC metastases were EGFR-positive. There was no concordant EGFR status between the primary and the metastatic sites. A strong discrepancy of EGFR status was noted between TMA and tissue sections. In conclusion, EGFR expression measured in tissue sections from primary CRC and their related metastases was found to be similar and frequent, but it was significantly underestimated by the TMA technique.

Adenocarcinoma↗

PubMed2006

An atlas of gene expression from seed to seed through barley development.

Assaying relative and absolute levels of gene expression in a diverse series of tissues is a central step in the process of characterizing gene function and a necessary component of almost all publications describing individual genes or gene family members. However, throughout the literature, such studies lack consistency in genotype, tissues analyzed, and growth conditions applied, and, as a result, the body of information that is currently assembled is fragmented and difficult to compare between different studies. The development of a comprehensive platform for assaying gene expression that is available to the entire research community provides a major opportunity to assess whole biological systems in a single experiment. It also integrates detailed knowledge and information on individual genes into a unified framework that provides both context and resource to explore their contributions in a broader biological system. We have established a data set that describes the expression of 21,439 barley genes in 15 tissues sampled throughout the development of the barley cv. Morex grown under highly controlled conditions. Rather than attempting to address a specific biological question, our experiment was designed to provide a reference gene expression data set for barley researchers; a gene expression atlas and a comparative data set for those investigating genes or regulatory networks in other plant species. In this paper we describe the tissues sampled and their transcriptomes, and provide summary information on genes that are either specifically expressed in certain tissues or show correlated expression patterns across all 15 tissue samples. Using specific examples and an online tutorial, we describe how the data set can be interrogated for patterns and levels of barley gene expression and how the resulting information can be used to generate and/or test specific biological hypotheses.

Databases, Genetic↗

PubMed2005

RhoC-GTPase is a novel tissue biomarker associated with biologically aggressive carcinomas of the breast.

BACKGROUND: There is a need for reliable predictors of breast cancer aggressiveness that will further refine the staging classification and help guide the implementation of novel therapies. We have identified RhoC as being nearly always overexpressed in the most aggressive form of breast cancer, inflammatory breast cancer (IBC); in subsequent work we identified RhoC to be a promising marker of aggressive behavior in breast cancers less than 1 cm in diameter. We hypothesized that RhoC expression would identify aggressive, non-IBC tumors breast cancer patients at any stage with worse outcomes defined as recurrence and/or metastasis. METHODS: We constructed four high-density tissue microarrays (TMAs) using 801 tissue cores from 280 patients. These tissues represent a wide range of normal breast and breast disease, including intraductal hyperplasia, ductal carcinoma in situ (DCIS), invasive carcinomas, and distant metastases. The TMAs were immunostained using a polyclonal anti-RhoC antibody developed in our laboratory. Cytoplasmic RhoC expression was scored as negative, weak, moderate, or strong by a previously validated scoring schema. RESULTS: RhoC expression increases with breast cancer progression. All samples of normal breast epithelium had negative to weak staining, whereas staining intensity increased in hyperplasia, DCIS, invasive carcinoma, and metastases (Kruskal-Wallis p < 0.001). In patients with invasive carcinoma, high RhoC expression was associated with features of aggressive behavior including high histologic grade, positive lymph nodes, and negative hormonal receptor status. High RhoC expression was a predictor of overall survival in patients with breast cancer (log rank test, p = 0.002) and was associated with 100% increase in the risk of death as compared to patients with low RhoC expression. Importantly, high RhoC was an independent predictor of poor response to doxorubicin-based chemotherapy with a hazard ratio of 3.1 and a 95% CI of 1.2-7.7 (p = 0.02). CONCLUSION: RhoC expression increases with breast cancer progression and RhoC protein level in tumor tissue is strongly associated with biologically aggressive invasive carcinomas of the breast. RhoC expression, if validated, may identify patients who are less likely benefit from doxorubicin therapy and suggests RhoC overexpression as a new target for intervention.

Biomarkers, Tumor↗

PubMed2006

Expression of protein elongation factor eEF1A2 predicts favorable outcome in breast cancer.

Breast cancer is the most common malignancy among North American women. The identification of factors that predict outcome is key to individualized disease management and to our understanding of breast oncogenesis. We have analyzed mRNA expression of protein elongation factor eEF1A2 in two independent breast tumor populations of size n = 345 and n = 88, respectively. We find that eEF1A2 mRNA is expressed at a low level in normal breast epithelium but is detectably expressed in approximately 50-60% of primary human breast tumors. We have derived an eEF1A2-specific antibody and measured eEF1A2 protein expression in a sample of 438 primary breast tumors annotated with 20-year survival data. We find that high levels of eEF1A2 protein are detected in 60% of primary breast tumors independent of HER-2 protein expression, tumor size, lymph node status, and estrogen receptor (ER) expression. Importantly, we find that high eEF1A2 is a significant predictor of outcome. Women whose tumor has high eEF1A2 protein expression have an increased probability of 20-year survival compared to those women whose tumor does not express substantial eEF1A2. In addition, eEF1A2 protein expression predicts increased survival probability in those breast cancer patients whose tumor is HER-2 negative or who have lymph node involvement.

Amino Acid Sequence↗

PubMed2007

Insulin receptor is an independent predictor of a favorable outcome in early stage breast cancer.

Fasting insulin is related to outcome in early breast cancer. We evaluated the expression of insulin receptor (IR) and its prognostic significance in patients with early stage breast cancer. Tumors from 191 patients with T1-3, N0-1, M0 breast cancer who were enrolled at a single center of a multicenter cohort study were used to construct microarrays with subsequent immunohistochemical evaluation of IR, IGF-IR, ER, PgR and HER2/neu. Correlation of biomarker expression with traditional prognostic factors, serum biochemistry (notably insulin) and clinical outcome was assessed. IR was strongly positive (Allred score = 8) in 54% of tumors. High IR expression significantly correlated with favorable prognostic markers (low tumor grade, lymph node negativity and progesterone receptor positivity) but not with fasting levels of circulating insulin. At a median follow-up of 9.1 years, high vs. low IR expression (an Allred score of 8 vs. 0-7) was associated with statistically significant improved distant disease-free survival (multivariate hazard ratio (HR) = 0.4; P = 0.027) and overall survival (multivariate HR = 0.26; P = 0.005). IR is highly expressed in the majority of early stage breast cancers but this expression is not clearly down-regulated in the presence of high insulin levels. Furthermore, high expression of IR is independently and significantly associated with more favorable clinical outcomes. Follow-up intervention research is recommended.

Adult↗

PubMed2006

The specificity of interphase FISH translocation probes in formalin fixed paraffin embedded tissue sections is readily assessed using automated staining and scoring of tissue microarrays constructed from murine xenografts.

Implementation of interphase fluorescence in situ hybridization (FISH) assays in the clinical laboratory requires validation against established methods. Validation tools in common use include exchange of consecutive sections with another institution that has already established the FISH assay, comparison with conventional banded metaphase cytogenetics, confirmation of specificity using probed normal metaphases, consecutive paraffin sections of a validation set tested by a reference laboratory, and specificity assessment against well characterized cell lines. We have investigated the feasibility of using tissue microarrays (TMA) constructed from murine xenografts as a preliminary specificity-screening tool for validation of interphase FISH assays. Cell lines currently in use for FISH controls are used to generate xenografts in SCID mice which are fixed in formalin and paraffin embedded. A TMA is constructed using duplicate donor cores from the xenograft blocks. Xenografts used represent a wide range of translocations used routinely for formalin fixed paraffin embedded sections evaluated by FISH. Probe cocktails (Abbott-Vysis), for several non-random translocations associated with hematologic neoplasms and soft tissue sarcomas have been used in this manner. On-line deparaffinization, cell conditioning, and prehybridization steps are automated using a staining workstation (Ventana Discovery XT); hybridization and stringency washes are performed manually offline. FISH-probed TMAs are tracked using a Metasystems image scanner and analyzed using classifiers specifically developed for each molecular abnormality. FISH results for each xenograft in the TMA correspond exactly to the genotype previously established for the parent cell line from which the xenograft was prepared. Moderate complexity tissue microarrays constructed from murine xenografts are excellent validation tools for initial assessment of interphase FISH probe specificity.

Animals↗

PubMed2006

The hydrolipidic ratio in age-related maturation of adipose tissues.

The hydrolipidic ratio (HLR) expresses the amount of water and fat in a tissue. HLR can be studied non-invasively in the living organism and can be mapped in different areas of the body with high spatial and temporal resolution. In the present work we have evaluated the HLR in different adipose tissue depots in young or adult rats using tissue arrays of fat fragments by 1H-spectroscopy. In young animals, the highest percentage of water (33%) was found in the interscapular brown adipose tissue (iBAT). Mesenteric fat (mWAT) also appeared highly hydrated (24%). The deposits composed of epididymal, retroperitoneal and pelvic white adipose tissue (eWAT, rWAT and pWAT, respectively) contained an amount of water ranging from 14% to 17%. In adult animals, a reduction of the water content was found in all the depots. In e/r/pWAT, the age-related maturation was characterized by large changes in adipocyte diameter accompanied by a small change in HLR. In the iBAT, the maturation was accompanied by small change in adipocyte diameter and a greater diminution of HLR. mWAT showed an intermediate pattern between e/r/pWAT and iBAT. In all the studied depots, an age-related increase in leptin expression was found. This increase was relatively low in iBAT (40%) and high in the e/r/pWAT (204-273%). The work expand the knowledge about the physiological significance of the HLR by 1H-spectroscopy.

Adipocytes↗

PubMed2006

Rapid and onsite BOD sensing system using luminous bacterial cells-immobilized chip.

A BOD monitoring system based on a bio-chip which immobilized luminous bacterium in micrometer-order holes were arrayed and fabricated by micro-machine techniques, was developed. The acrylic chip (3 cmx3 cm) comprises nine micro-holes (diameter: 700 microm or 1 mm, depth: 100 microm) arranged in a three by three array. Cells of the marine luminous bacterium, Photobacterium phosphoreum IFO 13896, which was grown at 15 degrees C for 15 h, were immobilized with 3% or 15% sodium alginate gel. BOD standard solutions or actual sample solution (approximately 10 microl) was fallen onto the cell-arrayed chip, and then the chip was incubated at 25 degrees C for 25 min. After incubation, bioluminescence from the each hole was gray-scaled and measured by a chemi-imager or newly developed onsite-type-monitoring system using a digital camera and a mobile-type personal computer. BOD values less than 16 ppm could detect by the chip, in particular, linear relationship at the concentrations between 0 and 16 ppm could be observed when luminous cells were immobilized with 3% sodium alginate gel. Steady bioluminescence was observed on the chip in the presence of BOD standard solution (GGA solution) which contained mineral elements. Furthermore, simultaneous detection of BOD values in various samples could be employed in the single chip. These results showed that the monitoring system with bio-chip could achieve high-through-put and onsite BOD detection. Our newly developed onsite-type BOD detection system which was used a digital camera and a (mobile) laptop computer was applied to measure and detect organic pollution due to biodegradable substances in wastewater treatment system. The same performance as the chemi-imager system was obtained for data of bioluminescence. The obtained BOD values showed a similar correlation with that of the conventional method for BOD determination (BOD5). These results suggested for successful achievement of high-though-put and onsite detection of BOD in practical.

Biosensing Techniques↗

PubMed2007

Evaluation of genetic stability of the SYT gene rearrangement by break-apart FISH in primary and xenotransplanted synovial sarcomas.

Synovial sarcomas (SS) are infrequent and morphologically heterogeneous soft tissue sarcomas. The t(X;18)(p11.2;q11.2), which results in fusion of the SYT gene at 18q11 with the SSX1, SSX2, or (rarely) SSX4 gene is a primary genetic event in 90% of SS. To determine whether the t(X;18) present in the original tumor is maintained in its passages, a dual-color break-apart FISH assay for SYT gene disruption was performed in two tissue microarrays (TMA) comprising eight molecularly confirmed primary SSs and their xenografts, which were followed for several generations. A simplified scoring system was applied to the FISH results of the primary and xenotransplanted SS to classify the FISH data into distinct groups. SYT disruption was identified in all eight primary SS and in all their passages without any significant differences among them, despite wide variations in xenotransplantation time between the primary tumors and their xenografts. The TMA-based FISH assay demonstrated genetic stability related to SYT gene rearrangement in primary and xenografted SS.

Animals↗

PubMed2006

SRC-3/AIB1 protein and gene amplification levels in human esophageal squamous cell carcinomas.

It has been suggested that the steroid receptor coactivatior-3 (SRC-3) gene, also known as AIB1, ACTR, RAC3, p/CIP and TRAM-1, located at 20q12, plays an oncogenic role in several types of human cancers. In this study, we examined the encoded protein expression of SRC-3 and its copy number in 221 human esophageal squamous cell carcinomas (ESCCs). In this ESCC series, the overexpression and increased copy number of SRC-3 gene was detected in 46 and 13% of ESCCs, respectively. In addition, overexpression of SRC-3 was observed more frequently in primary ESCCs in late T stages (T3/T4) than that in earlier T1/T2 stages (P<0.05), but no significant association of expression of SRC-3 and status of lymph node metastases was observed (P>0.05). These results suggest that overexpression of SRC-3, caused by gene amplification/gain or other molecular mechanisms, might provide a selective advantage for the development and local invasion of certain subsets of ESCC. In addition, a significant correlation (P<0.05) of overexpression of SRC-3 with increased cell proliferation (through detection of Ki-67 expression) was observed in these ESCCs. These findings suggest a potential role of SRC-3 in the control of ESCC cell proliferation; such may be responsible, at least in part, for tumorigenesis and/or progression of ESCC.

Adult↗