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Tissue Microarray (tissue + microarray)
Kinds of Tissue Microarray Terms modified by Tissue Microarray Selected AbstractsRecurrent copy number gain of transcription factor SOX2 and corresponding high protein expression in oral squamous cell carcinomaGENES, CHROMOSOMES AND CANCER, Issue 1 2010Kolja Freier Gene copy number aberrations are involved in oral squamous cell carcinoma (OSCC) development. To delineate candidate genes inside critical chromosomal regions, array-CGH was applied to 40 OSCC specimens using a microarray covering the whole human genome with an average resolution of 1 Mb. Gene copy number gains were predominantly found at 1q23 (9 cases), 3q26 (11), 5p15 (13), 7p11 (7), 8q24 (17), 11q13 (15), 14q32 (8), 19p13 (8), 19q12 (7), 19q13 (8), and 20q13 (9), whereas gene copy number losses were detected at 3p21-3p12 (15), 8p32 (11), 10p12 (8), and 18q21-q23 (10). Subsequent mRNA expression analyses by quantitative real time polymerase chain reaction found high mRNA expression of candidate genes SOX2 in 3q26.33, FSLT3 in 19p13.3, and CCNE1 in 19q12. Tissue microarray (TMA) analyses in a representative OSCC collection found gene copy number gain for SOX2 in 52% (115/223) and for CCNE1 in 31% (72/233) of the tumors. Immunohistochemical analyses on TMA sections of the corresponding proteins detected high expression of SOX2 in 18.1% (49/271) and of CyclinE1 in 23.3% (64/275) of tumors analyzed. These findings indicate that SOX2 and CCNE1 might be activated via gene copy number gain and participate in oral carcinogenesis. The combination of array-CGH with TMA analyses allows rapid pinpointing of novel promising candidate genes, which might be used as therapeutic stratification markers or target molecules for therapeutic interference. © 2009 Wiley-Liss, Inc. [source] A simple and economical method for the manual construction of frozen tissue arraysAPMIS, Issue 10 2010SHU-CHUAN TSAO Tsao S-C, Wu C-C, Wen C-H, Huang Y-C, Chai C-Y. A simple and economical method for the manual construction of frozen tissue arrays. APMIS 2010; 118: 739,43. Tissue microarray has been developed to enable multiple cores of tissue in one or more new paraffin blocks. Currently, almost all tissue microarrays are made by coring cylindrical tissues from formalin-fixed and paraffin-embedded tissues. The disadvantages of formalin-fixed and paraffin-embedded tissues include the poor preservation of antigenicity of certain proteins and mRNA degradation induced by the fixation and embedding process. However, frozen tissue array construction presents technical difficulties, and tissue array devices are expensive, particularly for small- and medium-sized laboratories. We describe a simple manual method for producing well-aligned tissue arrays by a capsule freeze method that allows us to successfully perform hematoxylin,eosin and immunohistochemical stain. All 120 tissue samples were collected and constructed into blocks by this capsule freeze method. The capsules were not affected during the sectioning process, and the capsule material always disappeared during the aqueous steps of the stain processing. The frozen tissue arrays were smoothly sectioned without the use of a tape transfer system and immunohistochemical study was performed with satisfactory results. This alternative method can be applied in any laboratory, and is both simple and economical. [source] Immunohistochemical characteristics of diffuse sclerosing variant of papillary carcinoma: comparison with conventional papillary carcinomaAPMIS, Issue 10 2010JA SEUNG KOO Koo JS, Shin E, Hong SW. Immunohistochemical characteristics of diffuse sclerosing variant of papillary carcinoma: comparison with conventional papillary carcinoma. APMIS 2010; 118: 744,52. Diffuse sclerosing variant of papillary carcinoma (DSVPC) is a rare variant of papillary thyroid carcinoma (PTC). It shows different clinicopathologic features to the conventional PTC, but the immunohistochemical characteristics of DSVPC are yet to be more clearly defined. The purpose of this study was to investigate the immunohistochemical features of DSVPC, which are different from those of PTC. Tissue microarray was constructed from the paraffin-embedded tissue of 49 DSVPC and 50 conventional PTC samples. Immunohistochemical stains for p63, p53, galectin-3, cytokeratin 19, ,-catenin, Bcl-2, EMA, E-cadherin, CD15, and CD56 were performed on each tissue microarray. Immunohistochemical stain for p63 was negative in all conventional PTCs, but 14 (28.6%) cases of DSVPC showed p63 expression (p = 0.000). p53 was expressed in 38 (76.0%) cases of conventional PTC and 21 (42.9%) cases of DSVPC (p = 0.001). Galectin-3 was expressed in all 50 cases of conventional PTC, but eight (16.3%) cases of DSVPC did not express galectin-3 (p = 0.003). EMA was expressed more in DSVPC (40.8%) than in conventional PTC (20.0%, p = 0.024). In univariate analyses, Bcl-2 positivity (p = 0.016) and EMA negativity (p = 0.036) in DSVPC were associated with shorter time interval to tumor recurrence, but there was no significance for the two in multivariate analyses. DSVPC, a rare variant of PTC, has different immunohistochemical features from the conventional PTC, showing higher expression rate of p63 and lower expression rate of p53. It also shows galectin-3 negativity and EMA positivity. [source] Phosphoinositide 3-kinase is not overexpressed in melanocytic lesionsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 3 2007Rajendra S. Singh Background:, Although various studies have stressed the role of phosphatase and tensin homologue deleted on chromosome 10 (PTEN)-PI3K-AKT pathway in the progression of melanocytic lesions, little is known about the expression pattern of PI3K in these lesions. Objective:, To investigate the expression pattern of PI3K in benign and dysplastic nevi, primary melanomas, and metastatic melanomas and the role of PTEN and PI3K in melanocytic tumor progression. Methods:, Tissue microarrays were constructed using formalin-fixed, paraffin-embedded archival tissue blocks from 89 melanocytic lesions: 17 benign nevi, 18 dysplastic nevi, 23 primary melanomas, and 31 metastatic melanomas. Expression of PTEN and PI3K (p85 and p110 subunits) was evaluated immunohistochemically, and the number of cells and labeling intensity were assessed semiquantitatively. Results:, Both benign and dysplastic nevi showed strong cytoplasmic staining with PTEN, which was subsequently less in melanomas and completely lost in the metastatic lesions. Eleven of 17 (64%) benign nevi, seven of 10 (70%) dysplastic nevi, four of 23 (17%) primaries, and one of 31 (3%) visceral or lymph node metastasis showed strong positivity. Loss of PTEN expression from benign and dysplastic nevi to melanoma was statistically significant (p = 0.001). Although few cells showed reactivity for phosphoinositide 3-kinase (PI3 kinase)-p85 subunit, strong positivity was not detected in the cytoplasm of benign, malignant, or metastatic lesions, except for a single visceral metastasis. Three of 13 (23%) nevi showed positivity for the p110 subunit. No positivity was observed in the dysplastic nevi. Two of 22 (9%) melanomas, one of 14 (7%) visceral metastasis, and three of 12 (25%) lymph node metastasis showed strong positivity. There was no statistical difference in PI3 kinase expression in benign and malignant melanocytic lesions (p = 0.2). Conclusion:, PI3K is not overexpressed in melanocytic lesions. [source] Expression of insulin-like growth factor-binding protein 2 in melanocytic lesionsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 10 2003Huamin Wang Background:, Insulin-like growth factor-1 (IGF-1) is one of the most critical proteins required for the survival, migration, and growth of melanoma cells. IGF-binding protein 2 (IGFBP2), which binds and regulates the function of IGF-1, is upregulated in a dose-dependent manner in melanoma cells treated with IGF-1, suggesting a possible role of IGFBP2 in the pathogenesis of melanoma. Methods:, Tissue microarrays were constructed using formalin-fixed, paraffin-embedded archival tissue blocks from 94 melanocytic lesions: 20 benign nevi, 20 dysplastic nevi, 23 primary melanomas, and 31 metastatic melanomas. IGFBP2 expression was evaluated immunohistochemically using a polyclonal antibody against the C-terminus of IGFBP2. The number of cells and labeling intensity were assessed semiquantitatively. Results:, Positive IGFBP2 labeling was observed in 5.0% of benign nevi, which was significantly lower than in dysplastic nevi (35.0%), primary melanomas (52.2%), or metastatic melanomas (54.8%) (p < 0.05). Among the IGFBP2-positive cases, moderate-to-strong immunostaining was observed in 64.7% of metastatic melanomas and 33.3% of primary melanomas. But none of the dysplastic nevi had moderate-to-strong immunostaining (p < 0.05). Conclusions:, Our study shows that IGFBP2 expression increases from benign and dysplastic nevi to primary and metastatic melanomas and suggests that it may play a role in melanoma progression. [source] Lack of protein expression of the simian virus 40 large T antigen in human lymphomas,,JOURNAL OF MEDICAL VIROLOGY, Issue 6 2008Philip Went Abstract Several studies have detected Simian virus 40 (SV40) deoxyribonucleic acid sequences in human tumor tissues, including lymphomas, mainly by the polymerase chain reaction, but these data were not confirmed by subsequent investigations. Regional differences in the distribution of the SV40 and/or technical difficulties have been taken into account to explain these divergent results, but because only a few such studies dealt with the expression of SV40 proteins in tumor tissues, we investigated the expression of the SV40 large T antigen in human lymphomas by immunohistochemistry. Tissue microarrays containing Non-Hodgkin's-lymphomas and Hodgkin's-lymphomas were constructed utilizing archival samples encompassing the years 1974,2001 from Italian, Swiss and Austrian patients. Expression of the SV40 large T antigen was analysed by highly specific and sensitive immunohistochemistry using a mouse monoclonal antibody. Protein expression of the large T antigen was not detected in 655 Non-Hodgkin's-lymphomas or in 337 Hodgkin's- lymphomas. The results suggest the absence of an association between SV40 large T antigen and human lymphomas. J. Med. Virol. 80:1112,1115, 2008. © 2008 Wiley-Liss, Inc. [source] Diagnostic utility of EWS break-apart fluorescence in situ hybridization in distinguishing between non-cutaneous melanoma and clear cell sarcomaPATHOLOGY INTERNATIONAL, Issue 9 2010Joon Seon Song Clear cell sarcoma (CCS) is a rare soft tissue sarcoma with morphological similarities to malignant melanoma (MM), but with a distinct genetic background that includes the chromosomal translocation t(12;22)(q13;q12). Clear cell sarcoma is often misdiagnosed as MM because of similarities in target locations and immunophenotypes. Eighteen cases with MM in non-cutaneous sites were subjected to fluorescence in situ hybridization (FISH) to assess EWS gene breakage. Tissue microarrays were constructed using formalin-fixed, paraffin-embedded tissue and the EWSR1 (22q12) dual-color, break-apart rearrangement probe (Vysis) was used. Two patients were classified as CCS with EWS gene rearrangement, with a mean of 67.5% positive cells per sample according to break-apart FISH. The remaining 16 patients lacked break-apart signals of the EWS gene. The presence of type 1 (EWS exon 8-ATF1 exon 4) fusion transcripts was confirmed in FISH-positive patients by RT-PCR. Retrospective analysis revealed that the masses were located in the foot and buttock, respectively. Morphologically, tumor cells were not typical for those of CCS or MM. Break-apart FISH is an accurate and convenient method for differentiating between MM and CCS. Molecular detection of EWS gene rearrangement, either by break-apart FISH or RT-PCR, is mandatory in subjects with melanotic tumors of soft tissue. [source] Distribution of Foxp3-, CD4- and CD8-positive lymphocytic cells in benign and malignant prostate tissueAPMIS, Issue 5 2010ALEXANDER VALDMAN Valdman A, Jaraj SJ, Compérat E, Charlotte F, Roupret M, Pisa P, Egevad L. Distribution of Foxp3-, CD4- and CD8-positive lymphocytic cells in benign and malignant prostate tissue. APMIS 2010; 118: 360,5. Foxp3 is a transcription factor that inhibits antitumor immune response and is expressed in regulatory T cells (Tregs). High levels of Tregs have been reported in several human cancers. This study investigates the distribution of cells positive for Foxp3, CD4 and CD8 in benign prostatic tissues and prostatic carcinoma. Tissue microarrays were constructed from radical prostatectomy specimens of 36 patients. From each patient, six cores were taken: two cores from cancer, one from benign tissue of each of the peripheral (PZ), transition (TZ) and central zones (CZ) and one from atrophy. Foxp3-, CD4- and CD8-positive cells were more common in cancer than in non-atrophic benign tissue (p < 0.01) and more common in atrophy than in non-atrophic PZ, but did not differ significantly between cancer and atrophy. Cells positive for Foxp3 and CD4 were less prevalent in CZ than in PZ and TZ. Tregs infiltrate more in prostate cancer (PC) than in benign tissue. Their presence in atrophy may have relevance for the hypothesis on atrophy as a potential precursor lesion of PC. CZ has the lowest Treg levels, and a possible role for the low rate of cancer in this zone remains to be investigated. [source] The prognostic value of intraepithelial and stromal CD3-, CD117- and CD138-positive cells in non-small cell lung carcinomaAPMIS, Issue 5 2010KHALID AL-SHIBLI Al-Shibli K, Al-Saad S, Andersen S, Donnem T, Bremnes RM, Busund L-T. The prognostic value of intraepithelial and stromal CD3-, CD117- and CD138-positive cells in non-small cell lung carcinoma. APMIS 2010; 118: 371,82. The major value of prognostic markers in potentially curable non-small cell lung carcinoma (NSCLC) should be to guide therapy after surgical treatment. Although tumor-infiltrating T lymphocytes and plasma cells have been documented in NSCLC, a clear association with clinical outcome, especially for the stromal component, has not been well established. The aim of this study was to elucidate the prognostic significance of these cells/markers in the epithelial and stromal compartments of NSCLC. Tissue microarrays from 335 resected, stage I-IIIA, NSCLC were constructed by duplicate cores from viable neoplastic epithelial and stromal areas. Immunohistochemistry was used to evaluate the infiltration of CD3+, CD117+ as well as CD138+ cells in epithelial and stromal areas. In univariate analyses, increasing numbers of stromal CD3+ (p = 0.001) and epithelial CD3+ cells (p = 0.004) correlated significantly with an improved disease-specific survival. No such relation was noted with CD3+ or CD117+ cells. In the multivariate analysis, stromal CD3+ cells was an independent prognostic factor for disease-specific survival (HR 1.925, CI 1.21,3.04, p = 0.005). Increased presence of the pan T-cell marker, CD3, which is an independent factor, correlates with improved clinical outcome in NSCLC. This prognostic impact of T cells is clearer in the tumor stroma. Neither plasma cells nor mast cells were prognostic indicators in our cohort. [source] Predicting outcome in minimally invasive (T1a and T1b) urothelial bladder carcinoma using a panel of biomarkers: a high throughput tissue microarray analysisBJU INTERNATIONAL, Issue 5 2007Paulette Mhawech-Fauceglia OBJECTIVE To evaluate the protein expression of fibroblast growth factor receptor-3 (FGFR3), hamartin, 14-3-3,, Aurora-A, and E-cadherin using immunohistochemistry (IHC) in a series of human bladder carcinomas and to evaluate their value in distinguishing T1a from T1b tumours and in predicting their behaviour, as T1 urothelial bladder tumours present great diagnostic and therapeutic challenges to pathologists and clinicians. PATIENTS, MATERIALS AND METHODS Tissue microarrays were constructed from 94 patients (Ta 20, T1a 31, T1b 14, and T2 29 patients) using tissue obtained at first disease presentation. RESULTS FGFR3 and 14-3-3, were the only markers that were significantly associated with tumour grade and 14-3-3, was significantly associated with tumour stage. Furthermore, none of these markers could help in distinguishing T1a from T1b tumours. After adjusting for the E-cadherin expression, FGFR3 expression was a significant factor in predicting the time to recurrence in T1a/T1b. Furthermore, among all the clinical variables, grade and depth of invasion were the only ones that had a significant value in predicting T1a/T1b tumour progression. CONCLUSIONS Even though the staging of T1 to T1a/T1b is not a common practice and it is not included in the Tumour-Node-Metastasis classification, our data clearly confirmed the importance of a proper sub-staging of T1 tumours whenever feasible. [source] Tissue microarrays in urologyBJU INTERNATIONAL, Issue 1 2004Iqbal S. Shergill First page of article [source] Fragile histidine triad protein, WW domain-containing oxidoreductase protein Wwox, and activator protein 2, expression levels correlate with basal phenotype in breast cancerCANCER, Issue 4 2009Gulnur Guler MD Abstract BACKGROUND: The expression of fragile histidine triad protein (Fhit) and WW domain-containing oxidoreductase protein (Wwox), tumor suppressors that are encoded by fragile (FRA) loci FRA3B and FRA16D, are lost concordantly in breast cancers. In the current study, the authors examined correlations among Fhit, Wwox, the activator protein 2 transcription factors AP2, and AP2,, cytokeratins 5 and 6 (CK5/6), epidermal growth factor receptor (EGFR), estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) and their associations with breast cancer phenotypes. METHODS: Tissue microarrays constructed from 837 breast cancer blocks were immunostained. Expression in >10% of tumor cells was considered positive for cytoplasmic CK5/6, membranous EGFR, and nuclear AP2, and AP2,. Cytoplasmic Fhit and Wwox staining was scored according to staining intensity. ER, PR, and HER-2 status of tumors was derived from records. Correlations among immunohistochemical markers and tumor subtypes were assessed by univariate and multivariate statistical methods. RESULTS: Triple-negative tumors had more frequent expression of EGFR, CK5/6 (P < .001), and AP2, (P = .003) and more frequent loss of Fhit and Wwox (P < .001), and an inverse correlation was observed between Fhit, Wwox expression and EGFR, ER, and PR expression (P < .001). Reduced Fhit expression was more common in HER-2-positive and AP2,-positive cases (P < .001 and P = .002, respectively). There was a direct correlation noted between Fhit and Wwox (P < .001) and a borderline positive relation between AP2, and AP2, (P = .054). CONCLUSIONS: The results from this investigation suggested that reduced expression levels of Fhit, Wwox, and nuclear AP2, have roles in the pathogenesis of basal-like differentiation in breast cancer. Alteration in the expression of fragile site genes occurs in most of these cancers and may contribute to defects in DNA repair, as observed in breast cancer 1 (BRCA1)-deficient cancers. Thus, DNA damage response checkpoint proteins may be targets for treatment. Cancer 2009. © 2009 American Cancer Society. [source] Cell microarray platform for anticancer drug development,DRUG DEVELOPMENT RESEARCH, Issue 5 2007Min-Jung Lee Abstract Pharmacodynamic assessment of whether a drug has interacted with and modified its target is an essential component of molecularly targeted clinical trials. Although many trials are written with the intent to assess tumor biopsies, if available, thus far the great majority of early drug trials have used peripheral blood mononuclear cells (PBMC) as a tumor surrogate. Typically, PBMC are studied by low-throughput techniques such as Western blot. We present the use of a cell-based tissue microarray for assessment of anticancer drug activity in vivo. We demonstrate the utility of this technique for analysis of protein hyperacetylation in response to treatment with the histone deacetylase inhibitor, SNDX-275 in PBMC treated in vitro and in PBMC and bone marrow aspirates from patients in Phase I clinical trials with SNDX-275. We demonstrate that the cell microarray can be used to measure drug response in a high-throughput manner, allowing analysis of an entire trial on one or two glass slides. The cell microarray technique brings the advantages of the tissue microarray platform to the pharmacodynamic assessment of single cells, such as those isolated from bone marrow aspirates, fine needle aspirates, or malignant effusions, and to analysis of PBMC, the most commonly studied surrogate in oncology trials. Drug Dev Res 68:226,234, 2007. Published 2007 Wiley-Liss, Inc. [source] PPFIA1 and CCND1 are frequently coamplified in breast cancerGENES, CHROMOSOMES AND CANCER, Issue 1 2010Ana-Maria Dancau Recently, amplification of PPFIA1, encoding a member of the liprin family located about 600 kb telomeric to CCND1 on chromosome band 11q13, was described in squamous cell carcinoma of head and neck. Because 11q13 amplification is frequent in breast cancer, and PPFIA1 has been suggested to contribute to mammary gland development, we hypothesized that PPFIA1 might also be involved in the 11q13 amplicon in breast cancer and contribute to breast cancer development. A tissue microarray containing more than 2000 human breast cancers was analyzed for gene copy numbers of PPFIA1 and CCND1 by means of fluorescence in situ hybridization. PPFIA1 amplification was found in 248/1583 (15.4%) of breast cancers. Coamplification with CCND1 was found in all (248/248, 100%) PPFIA1 -amplified cancers. CCND1 amplification without PPFIA1 coamplification was found in additional 117 (4.7%) tumors. Amplification of both PPFIA1 and CCND1 were significantly associated with high-grade phenotype (P = 0.0002) but were unrelated to tumor stage (P = 0.7066) or nodal stage (P = 0.5807). No difference in patient prognosis was found between 248 CCND1/PPFIA1 coamplified tumors and 117 tumors with CCND1 amplification alone (P = 0.6419). These data show that PPFIA1 amplification occurs frequently in breast cancer. The higher incidence of CCND1 amplification when compared with PPFIA1, the lack of prognostic relevance of coamplifications, and the fact that PPFIA1 amplification was found exclusively in CCND1 -amplified cancers suggest that PPFIA1 gene copy number changes represent concurrent events of CCND1 amplification rather than specific biological incidents. © 2009 Wiley-Liss, Inc. [source] Genomic and immunophenotypical differences between hepatocellular carcinoma with and without cirrhosisHISTOPATHOLOGY, Issue 6 2010Maria S Tretiakova Tretiakova M S, Shabani-Rad M T, Guggisberg K, Hart J, Anders R A & Gao Z-h (2010) Histopathology,56, 683,693 Genomic and immunophenotypical differences between hepatocellular carcinoma with and without cirrhosis Aims:, To compare the expression of genes involved in p53, Wnt/,-catenin, and retinoblastoma (Rb) 1 pathways between cirrhosis-associated hepatocellular carcinoma (HCC-C) and hepatocellular carcinoma arising in non-cirrhotic liver (HCC-NC). Methods and results:, The gene expression profile was analysed using oligo-DNA arrays, and then validated at protein level in a tissue microarray using immunohistochemistry. Compared with their background non-neoplastic liver tissue, HCC-C showed a significantly higher rate of p53, ,-catenin (protein only) and cyclin D1 expression, whereas HCC-NC showed a significantly higher rate of p21Waf1/cip1 and p27Kip1 expression. HCC-C had a significantly higher rate of p53 expression and a significantly lower rate of p21waf1/cip1 expression than HCC-NC. There was no statistically significant association between the expression of genetic markers and tumour histological grade, underlying aetiology, or lymphovascular invasion. Aberrant ,-catenin expression was more commonly seen in single tumours in comparison with multiple tumours. Increased p16INK4 and p21waf1/cip1 expression was more commonly observed in large-sized tumours (>50 mm) than small-sized tumours. Conclusions:, Alteration of the p53 pathway plays a more important role in the pathogenesis of HCC-C, whereas alterations in cell cycle regulators p21waf1/cip1 and p27Kip1 play a more important role in the pathogenesis of HCC-NC. [source] Alterations in Barrett's-related adenocarcinomas: A proteomic approachINTERNATIONAL JOURNAL OF CANCER, Issue 6 2008DunFa Peng Abstract In this study, we applied high-resolution, two-dimensional, gel electrophoresis and matrix-assisted laser desorption/ionization, time-of-flight and tandem mass spectrometry analysis (MALDI TOF MS) to identify novel proteins that are involved in Barrett's tumorigenesis. We analyzed 12 primary tissue samples that included 8 Barrett's-related adenocarcinomas (BA) and 4 normal mucosae samples. Twenty-three spots were consistently altered (,2-fold) in at least half of the tumors when compared with all normal samples and thus subjected to further analysis. The MALDI TOF MS analysis demonstrated biologically interesting upregulated proteins such as ErbB3, Dr5 and Cyclin D1 as well as several members of the zinc finger proteins (Znf146, Znf212 and Znf363). Examples of downregulated proteins included Lgi1 and Klf6. We selected four proteins (ErbB3, Dr5, Znf146 and Lgi1) that are novel for BAs for validation using quantitative real-time reverse-transcription PCR on 39 BA tissue samples when compared with normal samples. We demonstrated mRNA upregulation of ERBB3 (51.3%), DR5 (41%) and ZNF146 (30.7%) and downregulation of LGI1 (100%) in BA. We have further validated the protein overexpression of ErbB3, Dr5 and Znf146, using immunohistochemical (IHC) analysis on a tissue microarray that contained 75 BAs and normal gastric and esophageal mucosae samples. BA tissue samples demonstrated overexpression of ErbB3 (42%), Dr5 (90%) and Znf146 (30%) when compared with normal tissues. In conclusion, we have identified and validated several novel proteins that are involved in Barrett's carcinogenesis. © 2007 Wiley-Liss, Inc. [source] Immunohistochemical patterns in rectal cancer: Application of tissue microarray with prognostic correlationsINTERNATIONAL JOURNAL OF CANCER, Issue 6 2004Eva Fernebro Abstract We utilized the high-throughput tissue microarray method to characterize immunohistochemical expression patterns with correlations to prognosis in rectal cancer. Immunostaining for the markers Ki-67, Bcl-2, p53, EGFR, E-cadherin, ,-catenin, MLH1 and MSH2 was performed in 269 rectal cancers. Expression profiles were correlated to metastasis-free survival. Immunostaining revealed frequent upregulation and/or aberrant staining patterns for several of the markers, but Ki-67, p53, Bcl-2 and EGFR did not show any correlation to prognosis. However, reduced membranous staining for ,-catenin (p = 0.04), lack of cytoplasmic staining for ,-catenin (p = 0.04), reduced membranous staining for E-cadherin (p = 0.02) and lack of cytoplasmic staining for E-cadherin (p = 0.02) correlated with metastatic disease. Multivariate analysis including the factors Dukes' stage and tumor differentiation grade demonstrated increased risk of metastatic disease in tumors with lack of cytoplasmic staining for ,-catenin (HR = 3.1, p = 0.02), reduced membranous staining for ,-catenin (HR = 1.7, p = 0.06) and reduced membranous staining for E-cadherin (HR = 2.1, p = 0.06). Loss of MMR protein expression was confirmed to be a rare event in rectal cancer with loss of MLH1 staining in 3% and MSH2 in 1% of the tumors. The lack of prognostic information contributed by most of these markers suggests that single markers for prognosis may be of limited value in rectal cancer. However, altered expression of ,-catenin and E-cadherin correlated with metastatic disease, and these markers may have prognostic importance in rectal cancer. © 2004 Wiley-Liss, Inc. [source] Expression of retinoic acid receptor , in dermatofibrosarcoma protuberansJOURNAL OF CUTANEOUS PATHOLOGY, Issue 11 2009Zhou Xiaoli Background:, Retinoic acid receptor , (RAR ,) has been shown to act as a tumor suppressor in many solid human tumors. To investigate the putative role of RAR , in dermatofibrosarcoma protuberans (DFSP), we examined the expression of RAR , in DFSPs and analyzed the correlation of expression patterns between RAR , and cyclooxygenase (COX)-2 as well as clinicopathological variables. Methods:, Using tissue microarray and immunohistochemistry, we evaluated nuclear RAR , staining and cytoplasm COX-2 staining in 53 DFSPs. Results:, 48 DFSPs (90.58%) were immunopositive for RAR ,, while 32 DFSPs (60.38%) were immunopositive for COX-2. RAR , staining was significantly inversely correlated with COX-2 staining (p < 0.001; r =,0.668). Conclusions:, Our data indicated that RAR , expressed in DFSPs and correlated with COX-2 expression. RAR , may be a potential therapeutic target for unresectable DFSP cases. [source] Frequent high telomerase reverse transcriptase expression in primary oral squamous cell carcinomaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 5 2007Kolja Freier Background:, Gene copy number gain of chromosomal arm 5p is frequently found in oral squamous cell carcinoma (OSCC) suggesting the activation of proto-oncogenes. TERT is a candidate gene encoding for human telomerase reverse transcriptase (hTERT). The aim of the present study was to elucidate the relevance of TERT copy number gain and high hTERT expression in OSCC. Methods:, Fluorescence in situ hybridization (FISH) for TERT and immunohistochemistry (IHC) for hTERT were performed to analyze TERT copy numbers and hTERT expression, respectively, on tissue microarray (TMA) sections including n = 247 OSCC and n = 105 pharyngeal and laryngeal squamous cell carcinomas (PSCC/LSCC). Results:, Increased hTERT protein expression was more frequently found in OSCC (71.1%, 155/218) than in PSCC/LSCC (36.0%, 35/89) (P < 0.001). By contrast, specific TERT amplifications were less common in OSCC (2.1%, 4/191) compared with PSCC/LSCC (9.9%, 8/81) (P = 0.047). Conclusions:, High hTERT expression is a frequent finding in OSCC. It might be a promising target for the development of specific anti-neoplastic therapy approaches. [source] Chromosome 1p and 19q status and p53 and p16 expression patterns as prognostic indicators of oligodendroglial tumors: A clinicopathological study using fluorescence in situ hybridizationNEUROPATHOLOGY, Issue 1 2007Yoon Kyung Jeon To verify the prognostic implications of the statuses of chromosome 1p and 19q and the expressions of p53, p16 and GFAP in oligodendrogliomas, we investigated these parameters and correlated the results with patient outcome. Twenty-seven cases of low-grade oligodendroglioma (LO) and 29 cases of anaplastic oligodendroglioma (AO) were analyzed by FISH for 1p and 19q status and by immunohistochemistry for p53, p16, and GFAP expression using a tissue microarray. Direct sequencing of the p53 gene was also performed. 1p deletion was observed in 39 of 56 patients (69.9%), and 19q deletion in 41 of 56 (73.2%). Combined loss of 1p and 19q was found in 38 of 56 (67.9%) and exhibited distinct concomitant deletion (P = 0.000). p53 overexpression was observed in 17 cases (30.3%), GFAP expression in 18 cases (32.1%), and p16 loss in 40 cases (74%) of oligodendrogliomas. The expressions of p53 and GFAP were more frequent in AO than in LO (P = 0.015 and 0.001). In contrast, p53 expression was more common in oligodendrogliomas with an intact 19q (P = 0.029), or an intact 1p (P = 0.071). Only five of 14 patients with p53 expression showed TP53 mutation, which was inversely correlated with 1p deletion (P = 0.036). Patients with combined loss of 1p and 19q exhibited better overall survival (P = 0.045). Patients with p53 expression without combined 1p and 19q loss showed poor overall survival (P < 0.000). However, TP53 mutation along with 1p and 19q status could not predict patient outcome. Patients with p16 loss without combined 1p and 9q loss showed poor overall survival (P = 0.011). Therefore, in oligodendrogliomas, the absence of the combined deletion of 1p and 19q and the aberrant expression of p53 or loss of p16 could be used as poor prognostic markers. [source] Fluorescence in situ hybridization analysis with a tissue microarray: ,FISH and chips' analysis of pathology archivesPATHOLOGY INTERNATIONAL, Issue 8 2010Haruhiko Sugimura Practicing pathologists expect major somatic genetic changes in cancers, because the morphological deviations in the cancers they diagnose are so great that the somatic genetic changes to direct these phenotypes of tumors are supposed to be correspondingly tremendous. Several lines of evidence, especially lines generated by high-throughput genomic sequencing and genome-wide analyses of cancer DNAs are verifying their preoccupations. This article reviews a comprehensive morphological approach to pathology archives that consists of fluorescence in situ hybridization with bacterial artificial chromosome (BAC) probes and screening with tissue microarrays to detect structural changes in chromosomes (copy number alterations and rearrangements) in specimens of human solid tumors. The potential of this approach in the attempt to provide individually tailored medical practice, especially in terms of cancer therapy, is discussed. [source] Downregulation of Krüppel-like factor 9 in human colorectal cancerPATHOLOGY INTERNATIONAL, Issue 6 2008Ling Kang Mammalian Sp and Krüppel-like factors (KLF), a family of zinc finger-containing transcription factors, are involved in growth control, proliferation, apoptosis and angiogenesis of a wide variety of tissues and cells. Several KLF have been linked to various types of human cancers, but the relationship between Krüppel-like factor 9 (KLF9) and colorectal cancer has not been explored. The purpose of the present study was to investigate KLF9 expression in human colorectal cancer tissue. KLF9 mRNA was detected on quantitative real-time reverse transcriptase,polymerase chain reaction (Q-PCR). Of the 50 cancerous tissues examined, 86% (43/50) expressed lower levels of KLF9 mRNA than individually matched normal mucosa (P < 0.0001). On western blot, reduced or absent expression of KLF9 protein was observed in 65% (13/20) of the samples (P < 0.01). A total of 81% (35/43) of normal samples had expression of KLF9 protein, whereas its protein was detected in only 9% (4/43) of tumor tissues (P < 0.001) on tissue microarray. These results indicate that KLF9 may be involved in the carcinogenesis of human colorectal cancer. [source] Immunohistopathological re-evaluation of adenocarcinoma of the lung with mixed subtypes using a tissue microarray technique and hierarchical clustering analysisPATHOLOGY INTERNATIONAL, Issue 12 2007Gehan Gamal To re-evaluate adenocarcinoma, mixed subtypes (ADMIX) of the lung, a total of 201 cases were classified into three main subgroups according to the most differentiated histological growth pattern; namely bronchioloalveolar carcinoma (BAC)-mixed, which was the most predominant (73.1%), papillary (PAP)-mixed (21.9%), and acinar-mixed (5%). The PAP-mixed was significantly male predominant and had more progressed clinicopathological features. A significant cytological difference was observed among the three subgroups. A tissue microarray was constructed and immunohistochemistry was undertaken using 15 biomarkers. Hierarchical clustering analysis was separately applied to the immunohistochemical results of ADMIX and ADMIX subgroups, and it was found that most acinar-mixed cases were placed in a separate cluster, while the BAC-mixed and PAP-mixed failed to form significant independent clusters. The antibody clustering profile for the acinar-mixed was clearly different from that for the BAC-mixed or PAP-mixed, but the PAP-mixed shared a dendrogram profile with the other two subgroups. Statistically, approximately half of the 15 biomarkers were significant for differentiating between ADMIX subgroups and between different histological growth patterns. In conclusion, ADMIX can be classified into three histopathological subgroups according to the most differentiated growth pattern, of which a PAP growth pattern might indicate more aggressive behavior than that of a BAC growth pattern. [source] Immunohistochemical study of the expression of adhesion molecules in ovarian serous neoplasmsPATHOLOGY INTERNATIONAL, Issue 2 2006Eun Yoon Cho To clarify possible roles of adhesion molecules including E-cadherin, ,- and ,-catenin, CD44s, CD44v6, CD56, and CD99 in ovarian serous neoplasms, an immunohistochemical study was undertaken for 23 benign, 40 borderline, and 95 malignant ovarian serous neoplasms using tissue microarray (TMA). Significantly reduced expression of E-cadherin, and overexpression of CD44s, CD56, and CD99 were more frequently observed in adenocarcinomas than in benign and borderline tumors. Expression of CD44v6 and nuclear ,- and ,-catenin were detected only in borderline tumors and adenocarcinomas. Reduced expression of E-cadherin was also correlated with high tumor grade (P = 0.03), presence of peritoneal seeding (P = 0.03), and low overall survival rate (P = 0.02). Overexpression of CD44s was significantly associated with high tumor grade (P = 0.04), advanced stage (P = 0.03), and low overall survival rate (P = 0.02). CD56 was increasingly expressed in the case of advanced stage (P = 0.005) and peritoneal seeding (P = 0.001). Nuclear staining for ,-catenin was correlated with tumor progression (P = 0.004) and advanced International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.02). Only CD44s expression and stage were correlated with overall survival in multivariate study. These results suggest that although E-cadherin, CD44s, CD56, and nuclear ,-catenin immunoexpression seem to be useful prognostic markers for serous neoplasm of the ovary, CD44s expression and FIGO stage are independent prognostic factors. [source] A strategy for high-resolution protein identification in surface-enhanced laser desorption/ionization mass spectrometry: Calgranulin A and chaperonin 10 as protein markers for endometrial carcinomaPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 7 2005Jingzhong Guo Abstract Surface-enhanced laser desorption/ionization-mass spectrometry (SELDI-MS) has conventionally been practiced on linear time of flight (TOF) which has low mass accuracy and resolution. Here we demonstrate in an examination of both malignant and nonmalignant endometrial tissue homogenates that high mass accuracy and resolution in the MS stage are crucial. Using a commercially available quadrupole/TOF (QqTOF), we were able to resolve two potential cancer markers, subsequently identified off-line as chaperonin 10 and calgranulin A, that differ by 8 Da in mass. Two off-line protein identification protocols were developed: the first was based on size-exclusion chromatography (SEC), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), protein extraction, trypsin digestion, and matrix-assisted laser desorption/ionization-tandem MS (MALDI-MS/MS); the second on SEC and shotgun nano-liquid chromatography (nanoLC)-MS/MS. Analyses on a cohort of 44 endometrial homogenates showed 22 out of 23 nonmalignant samples had nondetectable to very low abundance of chaperonin 10 and calgranulin A; 17 of the 21 malignant samples had detectable to abundant levels of both proteins. Immunohistochemical staining of a tissue microarray of 32 samples showed that approximately half of malignant endometrial tissues exhibited positive staining for calgranulin A in the malignant epithelium, while 9 out of 10 benign tissues exhibited negative epithelial staining. In addition, macrophages/granulocytes in malignant as well as nonmalignant tissues showed positive staining. No immunostaining occurred in stroma or myometrium. Calgranulin A, in combination with chaperonin 10 and other proteins, may eventually constitute a panel of markers to permit diagnosis and screening of endometrial cancer. [source] Expression of KiSS-1 Gene and its Role in Invasion and Metastasis of Human Hepatocellular CarcinomaTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 8 2009Zang Shengbing Abstract KiSS-1 has been identified as a putative metastasis-suppressor gene in human melanomas and breast cancer cell lines. Although loss of KiSS-1 expression has been associated with progression and poor prognosis of various cancers, the exact role of KiSS-1 expression in HCC is not well-defined. Our study investigated KiSS-1 expression levels in HCC and its role in invasion and metastasis of human HCC. The expression levels of KiSS-1 and MMP-9 protein were determined by tissue microarray (TMA) serial sections, immunohistochemistry and semi-quantitative image analysis. All clinical and histological data obtained were subjected to statistical analysis. The expression of KiSS-1 protein in HCC and intrahepatic metastasis lesions was significantly lower (P < 0.01) when compared with non-tumor liver tissue and normal liver tissue. Multivariate analysis revealed a significant inverse correlation between KiSS-1 expression and ,1 TNM stage, (F = 7.113, P < 0.01) and ,2intrahepatic metastasis (t = 2.898, P < 0.01). Loss of KiSS-1 in intrahepatic metastasis versus primary carcinomas was statistically significant (P<0.01). We also found a negative correlation between KiSS-1 and MMP-9 expression in HCC (r = -0.506, P < 0.01). We conclude that loss of KiSS-1 during HCC metastasis, along with a concomitant upregulation of MMP-9 suggests a possible mechanism for cell motility and invasion during HCC metastasis, with KiSS-1 emerging as a possible therapeutic target during HCC metastasis. Anat Rec, 292:1128,1134, 2009. © 2009 Wiley-Liss, Inc. [source] SPARC (Osteonectin) in Breast Tumors of Different Histologic Types and Its Role in the Outcome of Invasive Ductal CarcinomaTHE BREAST JOURNAL, Issue 3 2010Yi-Hsuan Hsiao MD Abstract:, The purpose of this study was to characterize the immunohistochemical distribution of secreted protein acidic and rich in cystein (SPARC) in benign and malignant breast tumors of different histologic types and define its association with the outcome of invasive ductal carcinoma (IDC) patients. A total of 286 samples of benign and malignant breast lesions between 1994 and 2005 were retrieved from National Taiwan University Hospital. Up to 11 years clinical follow-up data were available for 185 patients with IDC. Immunohistochemistry staining with SPARC was performed in tissue microarray or whole section. The association of expression of SPARC and cumulative overall survival of IDC patients were analyzed using Kaplan,Meier survival analysis and Cox regression analysis. Secreted protein acidic and rich in cystein was not expressed in benign breast phylloides and all benign breast tumors, while expressed in 17.2% of IDC, 85% of metaplastic carcinoma of the breast (MCB), and all malignant breast phylloides. Secreted protein acidic and rich in cystein was strongly expressed in mesenchymal components of MCB and expression levels in epithelial components were variable. The correlation of positive expression of SPARC and poor long-term survival in IDC is significant (p = 0.004). Individuals with positive SPARC expression had 2.34 times higher hazard of death compared with those with negative SPARC expression after adjusting for factors including positive lymph node, TNM tumor stage, estrogen receptor, and progesterone receptor. Secreted protein acidic and rich in cystein may be useful as a prognostic indicator for IDC. [source] Selective over-expression of fibroblast growth factor receptors 1 and 4 in clinical prostate cancer,THE JOURNAL OF PATHOLOGY, Issue 1 2007K Sahadevan Abstract Fibroblast growth factor receptors (FGFRs) mediate the tumourigenic effects of FGFs in prostate cancer. These receptors are therefore potential therapeutic targets in the development of inhibitors to this pathway. To identify the most relevant targets, we simultaneously investigated FGFR1,4 expression using a prostate cancer tissue microarray (TMA) and in laser capture microdissected (LCM) prostate epithelial cells. In malignant prostates (n = 138) we observed significant FGFR1 and FGFR4 protein over-expression in comparison with benign prostates (n = 58; p < 0.0001). FGFR1 was expressed at high levels in the majority of tumours (69% of grade 3 or less, 74% of grade 4 and 70% of grade 5), while FGFR4 was strongly expressed in 83% of grade 5 cancers but in only 25% of grade 1,3 cancers (p < 0.0001). At the transcript level we observed a similar pattern, with FGFR1 and FGFR4 mRNA over-expressed in malignant epithelial cells compared to benign cells (p < 0.0005 and p < 0.05, respectively). While total FGFR2 was increased in some cancers, there was no association between expression and tumour grade or stage. Transcript analysis, however, revealed a switch in the predominant isoform expressed from FGFR2IIIb to FGFR2IIIc among malignant epithelial cells. In contrast, protein and transcript expression of FGFR3 was very similar between benign and cancer biopsies. The functional effect of targeting FGFR4 in prostate cancer cells has not previously been investigated. In in vitro experiments, suppression of FGFR4 by RNA interference effectively blocked prostate cancer cell proliferation (p < 0.0001) and invasion (p < 0.001) in response to exogenous stimulation. This effect was evident regardless of whether the cells expressed the FGFR4 Arg388 or Gly388 allele. In parallel experiments, FGFR3 suppression had no discernible effect on cancer cell behaviour. These results suggest evidence of selective over-expression of FGFR1 and FGFR4 in clinical prostate cancer and support the notion of targeted inhibition of these receptors to disrupt FGF signalling. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Characterization and over-expression of chaperonin t-complex proteins in colorectal cancerTHE JOURNAL OF PATHOLOGY, Issue 3 2006C Coghlin Abstract The chaperonins are key molecular complexes, which are essential in the folding of proteins to produce stable and functionally competent protein conformations. One member of the chaperonin group of proteins is TCP1 (chaperonin containing t-complex polypeptide 1, or CCT), but little is known about this protein in tumours. In this study, we used comparative proteomic analysis to show that t-complex protein subunits TCP1 beta and TCP1 epsilon are over-expressed in colorectal adenocarcinomas. Monoclonal antibodies to these proteins were developed and the expression and cellular localization of these two proteins in colorectal cancer were analysed by immunohistochemistry on a colorectal cancer tissue microarray. In colorectal cancer, TCP1 beta cellular localization was exclusively cytoplasmic, whereas TCP1 epsilon staining was seen in both the nucleus and the cytoplasm. Both cytoplasmic TCP1 beta and cytoplasmic TCP1 epsilon were significantly over-expressed (p < 0.001 for each protein) in primary colorectal cancer and also showed increased expression with advancing Dukes' stage (p = 0.018 for TCP1 beta and p = 0.045 for TCP1 epsilon). A trend was also identified between over-expression of cytoplasmic TCP1 beta and reduced patient survival (p = 0.05). These results show that both TCP1 beta and TCP1 epsilon are over-expressed in colorectal cancer and indicate a role for TCP1 beta and TCP1 epsilon in colorectal cancer progression. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Geminin predicts adverse clinical outcome in breast cancer by reflecting cell-cycle progressionTHE JOURNAL OF PATHOLOGY, Issue 2 2004Michael A Gonzalez Abstract Geminin inhibits DNA replication by preventing Cdt1 from loading minichromosome maintenance (MCM) proteins onto DNA. The present study has investigated whether the frequency of geminin expression predicts clinical outcome in breast cancer. Immunohistochemistry was used first to examine geminin expression in normal and malignant breast tissue (n = 67). Correlations with cell-cycle parameters, pathological features, and clinical outcome were then determined using an invasive breast carcinoma tissue microarray (n = 165). Breast carcinomas were scanned for mutations (n = 61) and copy number imbalances (n = 241) of the geminin gene. Finally, the cell cycle distribution of geminin in breast cancer cells was investigated in vivo and in vitro. Despite a putative tumour suppressor function, it was found that increased geminin expression is a powerful independent indicator of adverse prognosis in invasive breast cancer. Both poor overall survival (p = 0.0002) and the development of distant metastases (p = 0.005) are predicted by high geminin expression, which performs better in this patient cohort than traditional factors currently used to determine prognosis and appropriate therapy. No mutations or deletions of the geminin gene and no evidence that a high frequency of protein expression is related to gene amplification were found. It is shown that geminin is expressed from S to M phase in breast carcinoma tissue and cell lines, disappearing at the metaphase,anaphase transition. While MCM proteins identify all non-quiescent cells, geminin identifies the sub-fraction that have entered S phase, but not exited mitosis, thereby indicating the rate of cell-cycle progression. It is suggested that this explains its unexpected value as a prognostic marker in breast cancer. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] | |||||||||||||||||||||||||||||||