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Results for “Tissue Array Analysis”

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PubMed2004

Stat3 upregulates MEK5 expression in human breast cancer cells.

The constitutive activation of signal transducer and activator of transcription 3 (Stat3) is frequently detected in breast cancer cell lines but not in normal breast epithelial cells. Stat3 has been classified as an oncogene, because constitutively active Stat3 can mediate oncogenic transformation in cultured cells and tumor formation in nude mice. Since Stat3 appears to play an important role in breast cancer, it is of interest to investigate Stat3-regulated genes and elucidate Stat3-mediated oncogenesis. In this study, we investigated the Stat3-regulated genes in human breast epithelial cells. Upon overexpression of Stat3-C, a constitutively active Stat3 form, in nonmalignant telomerase immortalized breast (TERT) cells, the total mRNA was extracted and subjected to Affymetrix microarray analysis. Our results showed that mitogen-activated protein kinase kinase 5 (MEK5) was markedly induced (more than 22-fold increase, P<0.001) by Stat3-C expression. RT-PCR result also demonstrated that MEK5 mRNA was significantly induced by Stat3-C in TERT cells. The upregulation of MEK5 by Stat3-C was further confirmed by Western blot in MCF10A breast epithelial cells. Furthermore, in MDA-MB-435s breast carcinoma cells, which express high levels of activated Stat3 and MEK5, MEK5 protein was significantly reduced by using Stat3 short interfering RNA. The reduction of MEK5 was consistent with Stat3 knockdown in this breast carcinoma cell line. We also investigated MEK5 expression in different breast carcinoma cell lines and breast cancer tissues using tissue array analysis. Compared with nonmalignant breast epithelial cells or normal tissues without constitutively active Stat3 signaling, MEK5 protein levels are remarkably higher in breast carcinoma cell lines and cancer tissues with constitutively activated Stat3. Taken together, our findings suggest that constitutively active Stat3 upregulates MEK5 in the breast epithelial cells. MEK5 may be one of the Stat3-regulated genes and plays its essential roles in oncogenesis mediated by aberrantly activated Stat3 signaling in breast carcinomatosis and malignancies.

Base Sequence↗

PubMed2006

Profiling bladder cancer using targeted antibody arrays.

Bladder cancer is a common malignancy requiring a high degree of surveillance because of the frequent recurrences and the poor clinical outcome of invasive disease. To date, serum biomarkers for bladder cancer lack optimal sensitivity and specificity to assist in diagnosis and disease categorization. Here, we designed antibody arrays for bladder cancer by selecting antibodies against targets differentially expressed in bladder tumors. Serum protein profiles measured by an antibody array containing 254 antibodies discriminated bladder cancer patients from controls (n = 95) with a correct classification rate of 93.7%. A second independent antibody array containing 144 antibodies revealed that protein profiles provide predictive information by stratifying patients with bladder tumors (n = 37) based on their overall survival (P = 0.0479). In addition, serum proteins, such as c-met, that were top ranked at identifying bladder cancer patients were associated with pathological stage, tumor grade, and survival when validated by immunohistochemistry of tissue microarrays containing bladder tumors (n = 173). This study provides experimental evidence for the use of several integrated technologies strengthening the process of biomarker discovery. Serum protein profiles obtained by antibody arrays represent comprehensive means for bladder cancer diagnosis and clinical outcome stratification, which could potentially assist in selection of cancer patients who would benefit from early, individualized therapeutic intervention.

Adult↗

PubMed2005

Tissue MicroArray analyses of pancreatic duodenal homeobox-1 in human cancers.

In previous studies, we demonstrated that rat insulin promoter (RIP)-driven gene therapy successfully targeted human pancreatic tumor PANC-1 cells and mouse insulinoma NIT-1 cells, which are both pancreatic duodenal homeobox-1 (PDX-1)-positive. The purpose of this study was to perform a human tissue array analysis to determine potential targets for RIP-driven gene therapy. A custom-designed tissue MicroArray analysis of various human cancer specimens was performed using a PDX-1 polyclonal antibody generated in our laboratory. The custom-designed Tissue MicroArray of human tumor specimens consists of human cancer specimens from different origins, such as the pancreas, breast, colon, prostate, kidney, liver, lung, and ovary. A panel of normal human specimens from 20 organs or tissues was used as a control. All tissues were fixed in formalin and embedded in paraffin. The immunohistochemistry studies of the cytoplasm and the nuclear expression levels were compared using the Loda method and blind reviews. Data are presented as the mean +/- SEM (p < 0.05 was considered significant by the unpaired student t-test). PDX-1 expression intensity was elevated in both benign and malignant tissues from the same patient with pancreas, breast, colon, prostate, and kidney cancers, whereas normal human tissues from control subjects without cancer did not express PDX-1. These results suggest that PDX-1 is an early marker for these cancers and could be potentially used as a diagnostic parameter and perhaps could be targeted by PDX-1-activated gene therapies, such as RIP-TK.

Adenocarcinoma↗

PubMed2001

Genomic organization and expression profile of the parvin family of focal adhesion proteins in mice and humans.

We have characterized the genomic organization and the expression pattern of alpha-, beta- and gamma-parvin, a novel family of focal adhesion proteins, in mice and humans. alpha-Parvin is nearly ubiquitously expressed, beta-parvin is preferentially expressed in heart- and skeletal muscle, and gamma-parvin in lymphoid tissues. Parvins display diverse patterns of developmental regulation. The alpha-form is present throughout mouse development, beta-parvin is gradually upregulated and gamma-parvin is downregulated at embryonic day 11. The human alpha-parvin gene (PARVA), extending over 160 kb, is located on chromosome 11. Both, the human beta-parvin gene (PARVB), which is over 145 kb long, and the gamma-parvin gene (PARVG) of a total length of about 25 kb are positioned on chromosome 22 with PARVG located about 12 kb downstream of the 3' end of PARVB. Multiple tissue array analysis indicates that parvins are expressed at reduced levels in cancer as compared to the corresponding normal tissues. Analysis of ESTs and PCR-amplified fragments reveals alternatively spliced and alternatively polyadenylated gene products. Mammalian parvins are likely to have arisen late in evolution from gene duplication as they share a remarkably similar exon/intron organization, which is different from the organization of the single genes encoding parvin-like proteins in Drosophila and Caenorhabditis.

Actinin↗

PubMed2004

NF-kappa B in the vascular progression of melanoma.

PURPOSE: To examine a model of melanoma progression based on vascular factors and the role of NF-kappa B in the vascular progression of melanoma. PATIENTS AND METHODS: A data set of 526 patients from the University of California San Francisco Melanoma Center with 2 years of follow-up or first relapse was studied. The impact of the presence or absence of various prognostic factors on overall survival of melanoma patients was assessed using Cox regression and Kaplan-Meier analysis. A matched-pair analysis of NF-kappa B expression was performed in cases with vascular involvement and increased tumor vascularity versus matched controls lacking these factors. RESULTS: Cox regression analysis of factors evaluated by the American Joint Committee on Cancer Melanoma Staging Committee reproduced the powerful impact of tumor thickness and ulceration in this data set. With the inclusion of vascular factors such as tumor vascularity and vascular involvement, ulceration was no longer significant in predicting overall survival. By multivariate analysis, vascular involvement and tumor vascularity were the strongest predictors of melanoma outcome. Tumor vascularity seems to be a precursor of both vascular involvement and ulceration. A matched-pair tissue array analysis demonstrated the significant correlation between overexpression of NF-kappa B-p65 and the development of vascular factors. CONCLUSION: Vascular factors play an important role in the progression of malignant melanoma. Ulceration may be a surrogate marker for the interactions between melanoma and the tumor vasculature. NF-kappa B seems to play an important role in the development of these factors.

Biomarkers, Tumor↗

PubMed2006

High-throughput zebrafish histology.

The morphological effects of mutation and disease are often critical to our understanding of normal and abnormal function. The power and popularity of zebrafish as a forward and reverse genetic vertebrate model system, combined with its small size, have made it an ideal model in which to study the genetics of histologically scorable phenotypes. The presence of multiple tissue types in this organism's small larvae also makes it a potentially important model for toxicological analysis. Studying histological phenotypes is greatly enhanced by high-throughput methods of histology. Here, we describe details of high-throughput histology of the zebrafish using larval arrays, along with recent advances in mold design and discussion of work in progress that will lead to easier ways for people in the field to more rapidly score phenotypes in arrays. These detailed descriptions, together with the troubleshooting guide, should enable any laboratory with ties to a histology facility to perform high-throughput histology of zebrafish.

Animals↗

PubMed2003

Loss of the tight junction protein claudin-7 correlates with histological grade in both ductal carcinoma in situ and invasive ductal carcinoma of the breast.

Claudins are transmembrane proteins that seal tight junctions, and are critical for maintaining cell-to-cell adhesion in epithelial cell sheets. However, their role in cancer progression remains largely unexplored. Here, we report that Claudin-7 (CLDN-7) expression is lower in invasive ductal carcinomas (IDC) of the breast than in normal breast epithelium, as determined by both RT-PCR (9/10) and Western analysis (6/8). Immunohistochemical (IHC) analysis of ductal carcinoma in situ (DCIS) and IDC showed that the loss of CLDN-7 expression correlated with histological grade in both DCIS (P<0.001, n=38) and IDC (P=0.014, n=31), occurring predominantly in high-grade (Nuclear and Elston grade 3) lesions. Tissue array analysis of 355 IDC cases further confirmed the inverse correlation between CLDN-7 expression and histological grade (P=0.03). This pattern of expression is consistent with the biological function of CLDN-7, as greater discohesion is typically observed in high-grade lesions. In line with this observation, by IHC analysis, CLDN-7 expression was lost in the vast majority (13/17) of cases of lobular carcinoma in situ, which is defined by cellular discohesion. In fact, inducing disassociation of MCF-7 and T47D cells in culture by treating with HGF/scatter factor resulted in a loss of CLDN-7 expression within 24 h. Silencing of CLDN-7 expression correlated with promoter hypermethylation as determined by methylation-specific PCR (MSP) and nucleotide sequencing in breast cancer cell lines (3/3), but not in IDCs (0/5). In summary, these studies provide insight into the potential role of CLDN-7 in the progression and ability of breast cancer cells to disseminate.

Breast↗

PubMed2002

Insights into the pathobiology of hepatitis C virus-associated cirrhosis: analysis of intrahepatic differential gene expression.

The pathogenesis of hepatitis C virus (HCV)-associated liver injury involves many genes from multiple pathogenic pathways. cDNA array analysis, which examines the expression of many genes simultaneously, was used to achieve new insights into HCV liver injury. Membrane-based cDNA arrays of 874 genes compared HCV-associated cirrhosis with autoimmune hepatitis-associated cirrhosis as an inflammatory and cirrhotic control, and with nondiseased liver tissue. Array analysis identified many differentially expressed genes that are important in inflammation, fibrosis, proliferation, signaling, apoptosis, and oxidative stress. Genes up-regulated in HCV-associated cirrhosis were predominantly associated with a Th1 immune response, fibrosis, cellular proliferation, and apoptosis. Novel observations of differential gene expression included increased expression of secreted apoptosis-related protein 3, a Wnt pathway gene possibly involved in cellular apoptosis. EMMPRIN (CD147) and discoidin domain receptor 1 (CD167) were also shown to be increased and are likely to play a role in liver fibrosis. Real-time quantitative reverse transcriptase-polymerase chain reaction confirmed the increased expression of 15 genes. The comparison of HCV cirrhosis with autoimmune hepatitis cirrhosis showed a marked difference in the apoptosis-associated gene profile with HCV cirrhosis characterized by increased proapoptotic gene expression whereas autoimmune hepatitis was characterized by increased expression of both antiapoptotic and proapoptotic genes. Furthermore, expression of beta-catenin and the fibrosis-associated protein EMMPRIN were localized by immunohistochemistry to the plasma membranes of hepatocytes and biliary epithelium. In conclusion, HCV-associated cirrhosis was characterized by a proinflammatory, profibrotic, and proapoptotic gene expression profile.

Adult↗

PubMed2006

A comparison of immunohistochemical stain quality in conventional and rapid microwave processed tissues.

Same-day turnaround of pathology specimens is desirable in this era of managed care, and rapid microwave tissue processing produces histologic features of a quality equivalent to overnight processing. We studied whether microwave-assisted rapid tissue processing adversely affects the quality of immunohistochemical staining. We selected 30 specimens (20 neoplastic and 10 nonneoplastic) from our routine surgical pathology workload. Paired large tissue blocks were made from each specimen type, one for microwave-assisted rapid processing and one for conventional processing. Two microarrays of 60 punches each were made from the donor blocks. The microarray blocks were examined for intensity and extent of staining by 44 commonly used antibodies. Slides were reviewed independently by 2 pathologists blinded to the type of processing used. In 5,280 tissue punches examined, we found a high degree of concordance in quality, as measured by intensity and extent of immunohistochemical staining, between microwave and routinely processed tissues. Our study demonstrates that quality of immunohistochemical staining is similar between rapid microwave and conventional processing. The potential need for immunohistochemical analysis is not a contraindication for microwave-assisted rapid tissue processing.

Histocytological Preparation Techniques↗

PubMed2006

Theory and implementation of an electronic, automated measurement system for images obtained from immunohistochemically stained slides.

OBJECTIVE: To develop and implement an Internet-based, automated image measurement system for immunohistochemically stained slides including fluorescence images in online and off-line modes. STUDY DESIGN: An image analyzing system was developed that automatically measures digitized images obtained from immunohistochemically stained slides. It is divided into a common server platform and a specific image quantification system based upon DIAS (University of Jena). After registration, the user fills in an input data form and attaches images to be measured. The server periodically transfers the data to the measurement system. The measurement works on dynamic thresholding and active sampling of objects visualized by fluorescence and conventional chromogens. It includes stereologic algorithms, object quantification, syntactic structure analysis and quality assurance. RESULTS: The system has been tested for diaminobenzidene, alkaline phosphatase and fluorescence images (FITC, etc.). The reproducibility and stability of the system are > 98%. The series of successfully measured images comprises > 1,000 images in total in the online and off-line modes. CONCLUSION: An Internet-based automated image measurement system has been developed that offers worldwide access to the major requests for quantification of immunohistochemically stained slides-tissue array analysis, nuclear stains (MIB, hormones), membrane stains (CerbB2), vascularization and fluorescence in situ hybridization.

Anatomy, Cross-Sectional↗

PubMed2005

The p270 (ARID1A/SMARCF1) subunit of mammalian SWI/SNF-related complexes is essential for normal cell cycle arrest.

Mammalian SWI/SNF-related complexes are ATPase-powered nucleosome remodeling assemblies crucial for proper development and tissue-specific gene expression. The ATPase activity of the complexes is also critical for tumor suppression. The complexes contain seven or more noncatalytic subunits; only one of which, hSNF5/Ini1/BAF47, has been individually identified as a tumor suppressor thus far. The noncatalytic subunits include p270/ARID1A, which is of particular interest because tissue array analysis corroborated by screening of tumor cell lines indicates that p270 may be deficient in as many as 30% of renal carcinomas and 10% of breast carcinomas. The complexes can also include an alternative ARID1B subunit, which is closely related to p270, but the product of an independent gene. The respective importance of p270 and ARID1B in the control of cell proliferation was explored here using a short interfering RNA approach and a cell system that permits analysis of differentiation-associated cell cycle arrest. The p270-depleted cells fail to undergo normal cell cycle arrest on induction, as evidenced by continued synthesis of DNA. These lines fail to show other characteristics typical of arrested cells, including up-regulation of p21 and down-regulation of cyclins. The requirement for p270 is evident separately in both the up-regulation of p21 and the down-regulation of E2F-responsive products. In contrast, the ARID1B-depleted lines behaved like the parental cells in these assays. Thus, p270-containing complexes are functionally distinct from ARID1B-containing complexes. These results provide a direct biological basis to support the implication from tumor tissue screens that deficiency of p270 plays a causative role in carcinogenesis.

3T3 Cells↗

PubMed2006

WWOX protein expression in normal human tissues.

WWOX is a putative tumor suppressor gene that spans approximately a 1 Mb genomic region and is the site for the second most common chromosomal fragile site, FRA16D at 16q23. Various studies have focused on the expression of WWOX in human cancer mostly at the RNA level, but little is known about the normal pattern of WWOX protein expression in non-neoplastic tissues. In this study, a comprehensive analysis of WWOX protein expression in normal tissues was performed by means of immunohistochemistry utilizing a very specific anti-WWOX polyclonal antibody. We analyzed tissue cores of human samples representing more than 30 organs, using various tissue microarray (TMA) slides. Due to the potential role of WWOX in sex-steroid metabolism, whole sections from hormonally regulated organs like breast, ovaries, testes and prostate were also analyzed. The results from our study indicate that WWOX is preferentially highly expressed in secretory epithelial cells of reproductive, endocrine and exocrine organs, as well as in ductal epithelial cells from specific segments of the urinary system. Interestingly, we also observed significant WWOX protein expression in various cell types of neural origin including neurons, ependymal cells and astrocytes. No expression of WWOX was detected in adipose, connective, and lymphoid tissues, myelinized structures and blood vessels. By better defining the topographic distribution of WWOX in normal tissues this study provides some insight on the potential physiological role of this novel protein.

Humans↗

PubMed2005

Manual exfoliation of fresh tissue obviates the need for frozen sections for molecular profiling.

BACKGROUND: Simple, rapid tissue processing that preserves macromolecules will enhance translational research capabilities. Traditional fixative-based approaches for specimen preservation are ideal for histologic evaluation but are not conducive to molecular studies of nucleic acids and protein. Tissue cryosections preserve macromolecule integrity, but the process is labor intensive and technically challenging. To the authors' knowledge to date, an alternative method capable of retrieving cells while providing adequate histologic detail yet preserving macromolecule integrity has been lacking. In the current study, the authors evaluated the utility of using manual exfoliation of clinical tissue samples as a means of obtaining cells for molecular analysis. This technique possesses the advantages of fixed and frozen tissue sections without their drawbacks. This simple, rapid, nonfixative based technique is capable of preparing cells from human clinical material for further isolation without compromising the preservation of macromolecules in the tissue. METHODS: Cells from a variety of clinical resection specimens from solid tumors were directly scraped from the tissue samples using the edge of a glass microscope slide and smeared onto another slide for cytologic evaluation. The manually exfoliated cells were evaluated microscopically for cytologic quality and cellular quantity. Pure cell populations were procured by laser capture microdissection (LCM) with subsequent extraction of nucleic acids and proteins. The integrity and suitability of the recovered nucleic acids and proteins for molecular analysis were evaluated using the polymerase chain reaction (PCR), reverse transcriptase-PCR, and reverse-phase protein microarray, respectively. RESULTS: Manual exfoliation permits the selection of homogeneous cell populations by LCM based on well established cytologic characteristics. DNA and mRNA, of comparable quality to frozen sections, can be amplified from the manual exfoliation cells. Proteins of similar quality can be recovered using this technique and quantitated via reverse-phase protein microarray. CONCLUSIONS: Molecular macromolecules of high quality and sufficient quantity can be retrieved from human clinical samples using manual exfoliation and LCM to procure specific cell populations. The manual exfoliation technique does not destroy the original tissue source, thereby allowing subsequent formalin tissue fixation. The technique of manual exfoliation in conjunction with LCM can enable the molecular profiling of a sampled selected cell population. Because it does not destroy the original tissue, histologic correlation can be combined with molecular profiling.

Cell Separation↗

PubMed2006

Lipidomic analysis of twenty-seven prostanoids and isoprostanes by liquid chromatography/electrospray tandem mass spectrometry.

Prostanoids are potent mediators of many physiological and pathophysiological processes. Of the many analytical methodologies used for their qualitative and quantitative analysis, electrospray tandem mass spectrometry coupled to liquid chromatography (LC/ESI-MS/MS) offers a rapid, sensitive and versatile system applicable to lipidomic analyses. We have developed an LC/ESI-MS/MS assay for twenty-seven mediators including prostaglandins, prostacyclines, thromboxanes, dihydroprostaglandins and isoprostanes. The assay was liner over the concentration range 1-100 pg/microL. The limits of detection and quantitation were 0.5-50 and 2-100 pg, respectively, whilst recoveries were from 83-116% depending on the metabolite. The assay can be applied to the profiling of prostanoids produced by a variety of biological fluids and extracts including brain, liver, plasma and urine, thus facilitating our understanding of the role of these lipid mediators in health and disease, as well as assisting in drug development.

Animals↗

PubMed2006

Tissue microarray analysis of interleukin-20 expression.

Knowledge about the biological functions and clinical implications of interleukin (IL)-20, a recently discovered cytokine in the IL-10 family, is still incomplete. Our aim was to determine the distribution of IL-20 expression and to delineate the cell types that express IL-20 in healthy and neoplastic tissue, because this information will significantly affect the exploration of its pathophysiological roles. We used tissue microarray technology and an immunohistochemical survey using an anti-IL-20 monoclonal antibody to examine IL-20 expression in 36 non-neoplastic and 14 neoplastic tissues. IL-20 protein was positively stained in 30 non-neoplastic tissue types and five major cell types: epithelial cells, myoepithelial cells, endothelial cells, macrophages, and skeletal muscle cells. We also found that several types of tumor cells stained positive for IL-20, especially in squamous cell carcinoma of the skin, tongue, esophagus, and lung. Our data provide valuable references for further investigation of the biological functions and clinical implications of IL-20 in humans.

Gene Expression Profiling↗

PubMedDate not supplied

Tissue microarray analysis of EGFR and erbB2 copy number changes in ovarian tumors.

The objective of this study was to assess the implication of copy number changes of epidermal growth factor receptor (EGFR) and erbB2 genes in the etiology and progression of ovarian tumors. In our study, we used the highly reliable method of fluorescent in situ hybridization, applied on tissue microarray, containing 1006 ovarian tumors from different malignancy, histologic type and grade, and tumor stage, in order to analyze the correlations between gene copy number changes and tumor phenotype. We established copy number changes of erbB2 in 15.30% of malignant ovarian tumors-8.16% amplifications and 7.14% gains. The frequency of EGFR copy number changes was 10.67%-3.65% amplifications and 7.02% gains. EGFR gains occurred with approximately the same frequency in malignant (7.02%), low malignant potential (8.33%), and benign (7.19%) ovarian tumors. ErbB2 amplification was associated with clear cell type of ovarian cancer (P < 0.04). No amplification of EGFR and erbB2 genes was established in tumors with low malignant potency and in benign tumors. Regarding cancer phenotype, there was no statistically significant association between erbB2 copy number changes and histologic grade as well as tumor stage of ovarian cancer. EGFR gains are early events in ovarian tumorigenesis. Our results showed similar frequencies of EGFR gains in different grade tumors, while EGFR amplification increased from grades 1 to 2 to 3.

Adult↗

PubMed2004

Increased tissue microarray matrix metalloproteinase expression favors proteolysis in thoracic aortic aneurysms and dissections.

BACKGROUND: Little information is available regarding the role of matrix metalloproteinases (MMPs) in thoracic aortic aneurysms and dissections. We applied tissue microarray analysis to determine MMP profiles in a large group of surgically resected thoracic aneurysms and dissections. METHODS: Specimens from 47 patients undergoing a variety of surgical procedures for thoracic aneurysm (n = 30) and dissection (n = 17) were included. Expression of MMP-1, MMP-2, and MMP-9 and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were assessed by aortic tissue microarray immunostaining. Matrix metalloproteinase and TIMP expression in aortic tissue was compared with seven control aortic specimens, free of any vascular disease. RESULTS: Expression of MMP-1 and MMP-9 was significantly increased in aneurysm and aortic dissection patients compared with control specimens (p < 0.05). Expression of TIMP-2 was significantly increased in the entire patient group, compared with control specimens (p < 0.05). Aortic dissection patients had higher MMP-2 and MMP-9 expression than aortic aneurysm patients in areas of disease. Compared with control patients, the MMP-9 to TIMP-1 ratio (a relative index of proteolytic state) was increased in both the aortic aneurysm and dissection groups (p < 0.05). CONCLUSIONS: The increased MMP expression in aortic aneurysms and dissections indicates a metamorphosis in the aneurysm wall toward increased proteolysis compared with the normal aorta. Furthermore, we find even higher MMP-2 and MMP-9 presence in aortic dissection. In both aneurysms and dissections, this transformation to a proteolytic state likely plays an important pathophysiologic role in the development and progression of the aortic disease. The recognition of this pathophysiologic mechanism raises the potential for drug therapy to interrupt the cascade of events.

Aged↗

PubMed2006

Differential tissue and subcellular expressionof ERM proteins in normal and malignant tissues: cytoplasmic ezrin expression has prognostic signficance for head and neck squamous cell carcinoma.

BACKGROUND: Members of the ezrin-radixin-moesin (ERM) protein family regulate cellular shape, motility, and proliferation and potentially influence ability to metastasize. We investigated the correlation between ERM subcellular localization and survival in patients with squamous cell carcinoma (SCC) METHODS: Tissue microarrays (TMAs) were constructed from paraffin-embedded tissue. TMA sections were evaluated for ERM protein expression immunohistochemically. The results were compared across clinical and histopathologic variables RESULTS: ERM staining results for 47 patients showed that cytoplasmic ERM expression was prevalent in tumors (>92%). Whereas ezrin and moesin also localized to the membrane, only willin was found in the nucleus of tumors. Multivariable Cox regression analysis demonstrated that strong cytoplasmic ezrin expression was independently associated with poorer survival (p = .04, hazard ratio 1.82) CONCLUSIONS: Both level of expression and subcellular localization of ERM proteins may be important indicators of clinical outcome in SCC. This pilot study justifies the need for an expanded validation study of ERM proteins and clinical outcome.

Adult↗