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Fulltext Microarray dot electrodes utilizing dielectrophoresis for cell characterization

Yafouz B, Kadri NA, Ibrahim F

Sensors (Basel), 2013 Jul 12;13(7):9029-46.
PMID: 23857266 DOI: 10.3390/s130709029

During the last three decades; dielectrophoresis (DEP) has become a vital tool for cell manipulation and characterization due to its non-invasiveness. It is very useful in the trend towards point-of-care systems. Currently, most efforts are focused on using DEP in biomedical applications, such as the spatial manipulation of cells, the selective separation or enrichment of target cells, high-throughput molecular screening, biosensors and immunoassays. A significant amount of research on DEP has produced a wide range of microelectrode configurations. In this paper; we describe the microarray dot electrode, a promising electrode geometry to characterize and manipulate cells via DEP. The advantages offered by this type of microelectrode are also reviewed. The protocol for fabricating planar microelectrodes using photolithography is documented to demonstrate the fast and cost-effective fabrication process. Additionally; different state-of-the-art Lab-on-a-Chip (LOC) devices that have been proposed for DEP applications in the literature are reviewed. We also present our recently designed LOC device, which uses an improved microarray dot electrode configuration to address the challenges facing other devices. This type of LOC system has the capability to boost the implementation of DEP technology in practical settings such as clinical cell sorting, infection diagnosis, and enrichment of particle populations for drug development.

Matched MeSH terms: Tissue Array Analysis/instrumentation*
Whole-genome multiparametric screening to identify modulators of epithelial-to-mesenchymal transition

Said NA, Gould CM, Lackovic K, Simpson KJ, Williams ED

Assay Drug Dev Technol, 2014 Sep;12(7):385-94.
PMID: 25181411 DOI: 10.1089/adt.2014.593

Metastasis accounts for the poor prognosis of the majority of solid tumors. The phenotypic transition of nonmotile epithelial tumor cells to migratory and invasive "mesenchymal" cells (epithelial-to-mesenchymal transition [EMT]) enables the transit of cancer cells from the primary tumor to distant sites. There is no single marker of EMT; rather, multiple measures are required to define cell state. Thus, the multiparametric capability of high-content screening is ideally suited for the comprehensive analysis of EMT regulators. The aim of this study was to generate a platform to systematically identify functional modulators of tumor cell plasticity using the bladder cancer cell line TSU-Pr1-B1 as a model system. A platform enabling the quantification of key EMT characteristics, cell morphology and mesenchymal intermediate filament vimentin, was developed using the fluorescent whole-cell-tracking reagent CMFDA and a fluorescent promoter reporter construct, respectively. The functional effect of genome-wide modulation of protein-coding genes and miRNAs coupled with those of a collection of small-molecule kinase inhibitors on EMT was assessed using the Target Activation Bioapplication integrated in the Cellomics ArrayScan platform. Data from each of the three screens were integrated to identify a cohort of targets that were subsequently examined in a validation assay using siRNA duplexes. Identification of established regulators of EMT supports the utility of this screening approach and indicated capacity to identify novel regulators of this plasticity program. Pathway analysis coupled with interrogation of cancer-related expression profile databases and other EMT-related screens provided key evidence to prioritize further experimental investigation into the molecular regulators of EMT in cancer cells.

Matched MeSH terms: Tissue Array Analysis/methods
Identification of different subtypes of breast cancer using tissue microarray

Munirah MA, Siti-Aishah MA, Reena MZ, Sharifah NA, Rohaizak M, Norlia A, et al.

Rom J Morphol Embryol, 2011;52(2):669-77.
PMID: 21655659

Breast cancer may be classified into luminal A, luminal B, HER2+/ER-, basal-like and normal-like subtypes based on gene expression profiling or immunohistochemical (IHC) characteristics. The main aim of the present study was to classify breast cancer into molecular subtypes based on immunohistochemistry findings and correlate the subtypes with clinicopathological factors. Two hundred and seventeen primary breast carcinomas tumor tissues were immunostained for ER, PR, HER2, CK5/6, EGFR, CK8/18, p53 and Ki67 using tissue microarray technique. All subtypes were significantly associated with Malay ethnic background (p=0.035) compared to other racial origins. The most common subtypes of breast cancers were luminal A and was significantly associated with low histological grade (p<0.000) and p53 negativity (p=0.003) compared to HER2+/ER-, basal-like and normal-like subtypes with high histological grade (p<0.000) and p53 positivity (p=0.003). Luminal B subtype had the smallest mean tumor size (p=0.009) and also the highest mean number of lymph nodes positive (p=0.032) compared to other subtypes. All markers except EGFR and Ki67 were significantly associated with the subtypes. The most common histological type was infiltrating ductal carcinoma, NOS. Majority of basal-like subtype showed comedo-type necrosis (68.8%) and infiltrative margin (81.3%). Our studies suggest that IHC can be used to identify the different subtypes of breast cancer and all subtypes were significantly associated with race, mean tumor size, mean number of lymph node positive, histological grade and all immunohistochemical markers except EGFR and Ki67.

Matched MeSH terms: Tissue Array Analysis/methods*
Increased protein expression of p16 and cyclin D1 in squamous cell carcinoma tissues

Eshkoor SA, Ismail P, Rahman SA, Mirinargesi M, Oshkour SA

Biosci Trends, 2009 Jun;3(3):105-9.
PMID: 20103831

Abnormalities of Rb-pathway components are common in the formation of cancer. The immunostaining for cyclin D1 and p16 protein was applied on 1 mm serial tissue microarray (TMA) paraffin sections. Tissue microarray (TMAs) is potentially a good method to find the molecular features of the genes and expressions of them. The aim of this study was to evaluate the protein expressions of cyclin D1 and p16 genes in squamous cell carcinomas (SCCs) of skin and compare with the normal skin tissue. Twenty-five cases of cutaneous SCCs expressed cyclin D1 and p16 proteins. All SCCs samples on the slides showed positive protein expressions of cyclin D1 and p16 genes. Our findings suggested that the increased protein expressions of cyclin D1 and p16 genes might lead to aberrant expressions of these proteins in the affected tumor cells. This study demonstrated that cell cycle controlled deregulation and uncontrolled cell cycle progression might result in the carcinogenesis.

Matched MeSH terms: Tissue Array Analysis/methods
CIP2A expression in high grade prostatic intraepithelial neoplasia and prostate adenocarcinoma: a tissue mıcroarray study

Celikden SG, Baspinar S, Ozturk SA, Karaibrahimoglu A

Malays J Pathol, 2020 Aug;42(2):227-236.
PMID: 32860375

INTRODUCTION: CIP2A is an oncoprotein involved in the progression of several human malignancies. It has recently been described as a prognostic marker in many cancers. The present study aimed to investigate the immunohistochemical expression of CIP2A in benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN) and prostate cancer (PC), and to analyse the association with the clinicopathological parameters in PC cases to define its role in the development and progression of PC.
MATERIALS AND METHODS: Immunohistochemical staining for CIP2A was performed on the tissue microarray sections of 105 PC, 27 HGPIN and 27 BPH tissues. The CIP2A expression scores were compared with several clinicopathological parameters.
RESULTS: CIP2A was expressed in 96,2% of PC, 55,6% of HGPIN and 40,7% of BPH tissues. The expression of CIP2A in PC was significantly higher than in HGPIN (p<0.0001) and BPH (p<0.0001) cases. CIP2A expression score was significantly associated with Gleason score (p=0.032) and lymphovascular invasion (p=0.039). Nevertheless, there was no statistically significant association between the expression of CIP2A and perineural invasion, pT stage, metastasis and recurrence (p>0.05). Multivariate analysis indicated that GS, lymphovascular invasion, distant metastasis were independent prognostic factors for PC patients but, CIP2A expression score was not found to be a prognostic factor. Additionally, there was no significant difference between the survival times of patients according to CIP2A expression (p=0.174).
CONCLUSIONS: According to our results, the expression of CIP2A protein is increased in PC and its expression may be involved in the development, differentiation, and aggressiveness of PC. However, further studies are needed to confirm our findings and to clarify the role of CIP2A in the development of PC.

Matched MeSH terms: Tissue Array Analysis/methods*
Nuclear factor-kappa B subunits and their prognostic cancer-specific survival value in renal cell carcinoma patients

Ng KL, Yap NY, Rajandram R, Small D, Pailoor J, Ong TA, et al.

Pathology, 2018 Aug;50(5):511-518.
PMID: 29935727 DOI: 10.1016/j.pathol.2018.03.003

Better characterisation and understanding of renal cell carcinoma (RCC) development and progression lead to better diagnosis and clinical outcomes. In this study, expression of nuclear factor-kappa B (NF-κB) subunits: p65 (RelA), p105/p50, p100/p52, and cRel in RCC tissue were compared with corresponding normal kidney, along with tumour characteristics and survival outcome. Ninety-six cases of RCC with paired normal kidney were analysed. Clinicopathological data, demographics and survival data were available. Immunohistochemistry (IHC) for NF-κB subtypes was analysed using the Aperio digital pathology system for overall cellular expression and localisation. The prognostic cancer-specific survival value of the subunits in RCC patients was analysed. Approximately 50% of patients had clinical stage T1, with 22 patients having metastases at presentation. RCC subtypes were: clear cell (n = 76); papillary (n = 11); chromophobe (n = 5); clear cell tubulopapillary (n = 3); and one multilocular cystic RCC. Median follow up was 54.5 months (0.2-135), with 28 deaths at time of analysis. NF-κB p65 had higher overall and nuclear expressions, with lower overall and nuclear expressions of p50, p52 and cRel in RCC compared with normal kidney. Higher expressions of p65 (nuclear), p52 (overall and nuclear) and p50 (overall) correlated significantly with worse cancer-specific survival. This is the first large series of analysis of expression of NF-κB subunits in RCC. Especially with regards to the less studied subunits (p52, p50, cRel), our results allow a better understanding the role of NF-κB in RCC development and progression, and may pave the way for future targeted NF-κB subunit specific therapies.

Matched MeSH terms: Tissue Array Analysis/methods
Altered N-linked glycosylation in endometrial cancer

Mittal P, Briggs M, Klingler-Hoffmann M, Kaur G, Packer NH, Oehler MK, et al.

Anal Bioanal Chem, 2021 Apr;413(10):2721-2733.
PMID: 33222001 DOI: 10.1007/s00216-020-03039-z

It is well established that cell surface glycans play a vital role in biological processes and their altered form can lead to carcinogenesis. Mass spectrometry-based techniques have become prominent for analysing N-linked glycans, for example using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). Additionally, MALDI MS can be used to spatially map N-linked glycans directly from cancer tissue using a technique termed MALDI MS imaging (MALDI MSI). This powerful technique combines mass spectrometry and histology to visualise the spatial distribution of N-linked glycans on a single tissue section. Here, we performed N-glycan MALDI MSI on six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections and tissue microarrays (TMA) consisting of eight EC patients with lymph node metastasis (LNM) and twenty without LNM. By doing so, several putative N-linked glycan compositions were detected that could significantly distinguish normal from cancerous endometrium. Furthermore, a complex core-fucosylated N-linked glycan was detected that could discriminate a primary tumour with and without LNM. Structural identification of these putative N-linked glycans was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS). Overall, we observed higher abundance of oligomannose glycans in tumour compared to normal regions with AUC ranging from 0.85-0.99, and lower abundance of complex N-linked glycans with AUC ranges from 0.03-0.28. A comparison of N-linked glycans between primary tumours with and without LNM indicated a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2, in primary tumour with associated lymph node metastasis. In summary, N-linked glycan MALDI MSI can be used to differentiate cancerous endometrium from normal, and endometrial cancer with LNM from endometrial cancer without.

Matched MeSH terms: Tissue Array Analysis
Probing the colorectal cancer proteome for biomarkers: Current status and perspectives

Lee PY, Chin SF, Low TY, Jamal R

J Proteomics, 2018 09 15;187:93-105.
PMID: 29953962 DOI: 10.1016/j.jprot.2018.06.014

Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide. Biomarkers that can facilitate better clinical management of CRC are in high demand to improve patient outcome and to reduce mortality. In this regard, proteomic analysis holds a promising prospect in the hunt of novel biomarkers for CRC and in understanding the mechanisms underlying tumorigenesis. This review aims to provide an overview of the current progress of proteomic research, focusing on discovery and validation of diagnostic biomarkers for CRC. We will summarize the contributions of proteomic strategies to recent discoveries of protein biomarkers for CRC and also briefly discuss the potential and challenges of different proteomic approaches in biomarker discovery and translational applications.

Matched MeSH terms: Tissue Array Analysis
miR-205 in situ expression and localization in head and neck tumors - a tissue array study

Nurul-Syakima AM, Learn-Han L, Yoke-Kqueen C

Asian Pac J Cancer Prev, 2014;15(21):9071-5.
PMID: 25422181

BACKGROUND: microRNAs are small non-coding RNA that control gene expression by mRNA degradation or translational inhibition. These molecules are known to play essential roles in many biological and physiological processes. miR-205 may be differentially expressed in head and neck cancers; however, there are conflicting data and localization of expression has yet to be determined.
MATERIALS AND METHODS: miR-205 expression was investigated in 48 cases of inflammatory, benign and malignant tumor tissue array of the neck, oronasopharynx, larynx and salivary glands by Locked Nucleic Acid in situ hybridization (LNA-ISH) technology.
RESULTS: miR-205 expression was significantly differentially expressed across all of the inflammatory, benign and malignant tumor tissues of the neck. A significant increase in miR-205 staining intensity (p<0.05) was observed from inflammation to benign and malignant tumors in head and neck tissue array, suggesting that miR-205 could be a biomarker to differentiate between cancer and non-cancer tissues.
CONCLUSIONS: LNA-ISH revealed that miR-205 exhibited significant differential cytoplasmic and nuclear staining among inflammation, benign and malignant tumors of head and neck. miR-205 was not only exclusively expressed in squamous epithelial malignancy. This study offers information and a basis for a comprehensive study of the role of miR-205 that may be useful as a biomarker and/or therapeutic target in head and neck tumors.

Matched MeSH terms: Tissue Array Analysis
Fulltext Colonic Mucosal Transcriptomic Changes in Patients with Long-Duration Ulcerative Colitis Revealed Colitis-Associated Cancer Pathways

Low END, Mokhtar NM, Wong Z, Raja Ali RA

J Crohns Colitis, 2019 May 27;13(6):755-763.
PMID: 30954025 DOI: 10.1093/ecco-jcc/jjz002

BACKGROUND AND AIMS: Patients with ulcerative colitis [UC] with long disease duration have a higher risk of developing colitis-associated cancer [CAC] compared with patients with short-duration UC. The aim of this study was to identify transcriptomic differences associated with the duration of UC disease.
METHODS: We conducted transcriptome profiling on 32 colonic biopsies [11 long-duration UC, ≥20 years; and 21 short-duration UC, ≤5 years] using Affymetrix Human Transcriptome Array 2.0. Differentially expressed genes [fold change > 1.5, p < 0.05] and alternative splicing events [splicing index > 1.5, p < 0.05] were determined using the Transcriptome Analysis Console. KOBAS 3.0 and DAVID 6.8 were used for KEGG and GO analysis. Selected genes from microarray analysis were validated using qPCR.
RESULTS: There were 640 differentially expressed genes between both groups. The top ten upregulated genes were HMGCS2, UGT2A3 isoforms, B4GALNT2, MEP1B, GUCA2B, ADH1C, OTOP2, SLC9A3, and LYPD8; the top ten downregulated genes were PI3, DUOX2, VNN1, SLC6A14, GREM1, MMP1, CXCL1, TNIP3, TFF1, and LCN2. Among the 123 altered KEGG pathways, the most significant were metabolic pathways; fatty acid degradation; valine, leucine, and isoleucine degradation; the peroxisome proliferator-activated receptor signalling pathway; and bile secretion, which were previously linked with CAC. Analysis showed that 3560 genes exhibited differential alternative splicing between long- and short-duration UC. Among them, 374 were differentially expressed, underscoring the intrinsic relationship between altered gene expression and alternative splicing.
CONCLUSIONS: Long-duration UC patients have altered gene expressions, pathways, and alternative splicing events as compared with short-duration UC patients, and these could be further validated to improve our understanding of the pathogenesis of CAC.

Matched MeSH terms: Tissue Array Analysis
Fulltext Glypican-3 is useful but not superior to Hep Par 1 in differentiating hepatocellular carcinoma from other liver tumours

Pour AM, Masir N, Rose IM

Malays J Pathol, 2016 Dec;38(3):229-233.
PMID: 28028292 MyJurnal

To assess the diagnostic utility of glypican-3 (GPC-3) in comparison to Hep Par 1 in the diagnosis of liver tumours, a cross-sectional study involving 66 resected liver tumours were tested for the protein expression of these markers by immunohistochemistry using monoclonal antibodies. Of the 66 cases, 26 (39.4%) were hepatocellular carcinoma (HCC), 4 (6.1%) were intrahepatic cholangiocarcinoma and 36 (54.5%) were metastatic tumours. Hep Par 1 and GPC-3 expressions in HCC were 24/26 (92.3%) and 19/26 (73.1%) respectively. In contrast, of non-HCC cases, only 2/40 cases (5.0%) expressed Hep Par 1, including a metastatic colorectal adenocarcinoma and a metastatic gastric adenocarcinoma. GPC-3 was expressed in 3/40 cases (7.5%), i.e. a metastatic adenocarcinoma of unknown origin, a metastatic gastric adenocarcinoma and an intrahepatic cholangiocarcinoma. The sensitivity and specificity for Hep Par 1 were 92.3% and 95% respectively while that of GPC-3 was 73.1% and 92.5% respectively. GPC-3 is a useful marker in the diagnosis of HCC. However it is not superior to Hep Par 1 in its sensitivity and specificity. We recommend that it is utilized together with Hep Par 1 as a panel in the diagnosis of HCC.

Matched MeSH terms: Tissue Array Analysis
Tissue microarray immunohistochemical profiles of p53 and pRB in hepatocellular carcinoma and hepatoblastoma

Azlin AH, Looi LM, Cheah PL

Asian Pac J Cancer Prev, 2014;15(9):3959-63.
PMID: 24935581

The tumour suppressor genes, p53 and pRb, are known to play important roles in neoplastic transformation. While molecular routes to the uncontrolled growth of hepatocytes, leading to primary liver cancer have generated considerable interest, the roles of p53 and pRb mutations in hepatocellular carcinoma (HCC) and hepatoblastoma (HB) remain to be clarified. We examined the immunohistochemical expression of p53 and pRb gene products in 26 HCC and 9 HB, sampled into tissue microarray blocks. 10 (38%) of 26 HCC showed > 10% tumour nuclear staining for p53 protein, 3 of these also being HbsAg positive. Conversely, none of 9 HB expressed nuclear p53 immunopositivity. Some 24 (92%) HCC and 8 (89%) HB showed loss of pRb nuclear expression. Two of the 26 HCC and one of the 9 HB showed >10% tumour nuclear staining for pRb protein. Our results suggest that p53 does not have an important role in the development of HB but may contribute in HCC. There is also loss of pRb expression in the majority of HCC and HB, supporting loss of pRb gene function in the hepatocarcinogenesis pathway. However, a comparison of the staining profiles of p53 and pRb proteins in HCC and HB did not reveal a consistent pattern to differentiate between the two types of tumours immunohistochemically. Hence the use of p53 and pRB protein expression has no contribution in the situation where there is a diagnostic difficulty in deciding between HCC and HB.

Matched MeSH terms: Tissue Array Analysis
Fulltext Immunohistochemical expression of MAP1LC3A and MAP1LC3B protein in breast carcinoma tissues

Othman EQ, Kaur G, Mutee AF, Muhammad TS, Tan ML

J Clin Lab Anal, 2009;23(4):249-58.
PMID: 19623642 DOI: 10.1002/jcla.20309

Autophagy is a protein degradation process within the cell and its deregulation has been linked to various diseases and the formation of cancer. One of the important proteins involved in the autophagy process is microtubule-associated protein 1 light chain 3 (MAP1LC3). The aims of this study were to determine the MAP1LC3A and MAP1LC3B protein expression in both normal and cancer breast tissues and to determine the relationship between the expression of these proteins and type of tissues. Immunohistochemistry assessments were carried out on tissue microarrays consisting of breast tissues. MAP1LC3A expression was detected in 52/56 of normal breast tissue cores and 65/67 of breast cancer tissue cores. MAP1LC3B expression was detected in 55/56 of normal breast tissue cores and 67/67 of breast cancer tissue cores. MAP1LC3A and MAP1LC3B protein are expressed in the majority of normal and cancer breast tissues. A large number of MAP1LC3A and MAP1LC3B positive breast cancer tissues cores have high proportion of stained cells (81-100%) as compared with normal breast tissues. However, a significantly higher number of breast cancer tissues were found to express the MAP1LC3A protein with strong immunoreactivity as compared with the normal tissues, suggesting that MAP1LC3A may play a role in breast cancer development.

Matched MeSH terms: Tissue Array Analysis
Comparison of protein-based cell-of-origin classification to the Lymph2Cx RNA assay in a cohort of diffuse large B-cell lymphomas in Malaysia

Phang KC, Akhter A, Tizen NMS, Rahman FA, Zahratul Azma R, Elyamany G, et al.

J Clin Pathol, 2018 Mar;71(3):215-220.
PMID: 28775174 DOI: 10.1136/jclinpath-2017-204548

AIMS: The cell of origin (COO) based molecular characterisation into germinal centre B-cell-like (GCB) and activated B-cell-like (ABC) subtypes are central to the pathogenesis and clinical course in diffuse large B-cell lymphoma (DLBCL). Globally, clinical laboratories employ pragmatic but less than ideal immunohistochemical (IHC) assay for COO classification. Novel RNA-based platforms using routine pathology samples are emerging as new gold standard and offer unique opportunities for assay standardisation for laboratories across the world. We evaluated our IHC protocols against RNA-based technologies to determine concordance; additionally, we gauged the impact of preanalytical variation on the performance of Lymph2Cx assay.
METHODS: Diagnostic biopsies (n=104) were examined for COO classification, employing automated RNA digital quantification assay (Lymph2Cx). Results were equated against IHC-based COO categorisation. Assay performance was assessed through its impact on overall survival (OS).
RESULTS: 96 (92%) informative samples were labelled as GCB (38/96; 40%) and non-GCB (58/96; 60%) by IHC evaluation. Lymph2Cx catalogued 36/96 (37%) samples as GCB, 45/96 (47%) as ABC and 15/96 (16%) as unclassified. Lymph2Cx being reference, IHC protocol revealed sensitivity of 81% for ABC and 75% for GCB categorisation and positive predictive value of 81% versus 82%, respectively. Lymph2Cx-based COO classification performed superior to Hans algorithm in predicting OS (log rank test, p=0.017 vs p=0.212).
CONCLUSIONS: Our report show that current IHC-based protocols for COO classification of DLBCL at UKM Malaysia are in line with previously reported results and marked variation in preanalytical factors do not critically impact Lymph2Cx assay quality.

Matched MeSH terms: Tissue Array Analysis
Low HIP1R mRNA and protein expression are associated with worse survival in diffuse large B-cell lymphoma patients treated with R-CHOP

Wong KK, Ch'ng ES, Loo SK, Husin A, Muruzabal MA, Møller MB, et al.

Exp Mol Pathol, 2015 Dec;99(3):537-45.
PMID: 26341140 DOI: 10.1016/j.yexmp.2015.08.019

Huntingtin-interacting protein 1-related (HIP1R) is an endocytic protein involved in receptor trafficking, including regulating cell surface expression of receptor tyrosine kinases. We have previously shown that low HIP1R protein expression was associated with poorer survival in diffuse large B-cell lymphoma (DLBCL) patients from Denmark treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). In this multicenter study, we extend these findings and validate the prognostic and subtyping utility of HIP1R expression at both transcript and protein level. Using data mining on three independent transcriptomic datasets of DLBCL, HIP1R transcript was preferentially expressed in germinal center B-cell (GCB)-like DLBCL subtype (P<0.01 in all three datasets), and lower expression was correlated with worse overall survival (OS; P<0.01) and progression-free survival (PFS; P<0.05) in a microarray-profiled DLBCL dataset. At the protein level examined by immunohistochemistry, HIP1R expression at 30% cut-off was associated with GCB-DLBCL molecular subtype (P=0.0004; n=42), and predictive of OS (P=0.0006) and PFS (P=0.0230) in de novo DLBCL patients treated with R-CHOP (n=73). Cases with high FOXP1 and low HIP1R expression frequency (FOXP1(hi)/HIP1R(lo) phenotype) exhibited poorer OS (P=0.0038) and PFS (P=0.0134). Multivariate analysis showed that HIP1R<30% or FOXP1(hi)/HIP1R(lo) subgroup of patients exhibited inferior OS and PFS (P<0.05) independently of the International Prognostic Index. We conclude that HIP1R expression is strongly indicative of survival when utilized on its own or in combination with FOXP1, and the molecule is potentially applicable for subtyping of DLBCL cases.

Matched MeSH terms: Tissue Array Analysis

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