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Immunosensing prostate-specific antigen: Faradaic vs non-Faradaic electrochemical impedance spectroscopy analysis on interdigitated microelectrode device

Ibau C, Arshad MKM, Gopinath SCB, Nuzaihan M N M, Fathil MFM, Shamsuddin SA

Int J Biol Macromol, 2020 Nov 01;162:1924-1936.
PMID: 32822729 DOI: 10.1016/j.ijbiomac.2020.08.125

This work explores Electrochemical Impedance Spectroscopy (EIS) detection for a highly-sensitive quantification of prostate-specific antigen (PSA) in Faradaic (f-EIS) and non-Faradaic modes (nf-EIS). Immobilization of monoclonal antibody specific to PSA (anti-PSA) was performed using 1-ethyl-3-dimethylaminopropylcarbodiimide hydrochloride and N-hydroxysuccinimide crosslinking agents in order to conjugate carboxylic (-COOH) terminated group of 16-Mercaptoundecanoic acid with amine (-NH3+) on anti-PSA epitope. This approach offers simple and efficient approach to form a strong, covalently bound thiol-gold (SAu) for a reliable SAM layer formation. Studies on the topographic of pristine Au-IDE surface were performed by Scanning Electron Microscopy and Energy Dispersive X-ray Spectroscopy techniques, meanwhile a 3-dimensional optical surface profiler, Atomic Force Microscopy and X-ray Photoelectron Spectroscopy techniques were used to validate the successful functionalization steps on the sensor transducer surface. Detection of PSA in f-EIS mode was carried out by measuring the response in charge transfer resistance (Rct) and impedance change (Z), meanwhile in nf-EIS mode, the changes in device capacitance was monitored. In f-EIS mode, the sensor reveals a logarithmic detection of PSA in a range of 100 ng/ml down to 0.01 ng/ml in Phosphate Buffered Saline with a recorded sensitivity of 2.412 kΩ/log10 ([PSA] ng/ml) and the limit of detection (LOD) down to 0.01 ng/ml. The nf-EIS detection mode yields a logarithmic detection range of 5000 ng/ml down to 0.5 ng/ml, with a sensitivity of 8.570 nF/log10 ([PSA] ng/ml) and an LOD of 0.5 ng/ml. The developed bio-assay yields great device stability, specificity to PSA and repeatability of detection that would pave its way for the future development into portable lab-on-chip bio-sensing system.

Matched MeSH terms: Biomarkers, Tumor/analysis
Cutaneous metastasis of hepatocellular carcinoma diagnosed by fine needle aspiration cytology and Hep Par 1 immunopositivity

Isa NM, Bong JJ, Ghani FA, Rose IM, Husain S, Azrif M

Diagn Cytopathol, 2012 Nov;40(11):1010-4.
PMID: 21563319 DOI: 10.1002/dc.21706

Cutaneous metastasis of hepatocellular carcinoma (HCC) is very rare, accounting for less than 0.8% of all known cutaneous metastases and occurring in 2.7-3.4% of HCCs. With less than 50 such cases reported worldwide, most of which were diagnosed histologically on excised lesions, it can only be expected that diagnosis made on cytological features alone would be challenging. We report a case of cutaneous metastasis of HCC diagnosed based on cytological features and confirmed by Hep Par 1 immunopositivity of the cell block material. An 81-year-old man, who was known to have unresectable HCC, presented with a 1-month history of painless, left nasal alae mass. The mass measured 1.5 cm in diameter, and was multilobulated with a central necrosis. Fine needle aspiration of the mass was done. Smears were cellular, comprising of malignant cells in loose clusters and aggregates as well as singly dispersed. The malignant cells displayed moderate nuclear pleomorphism, occasional prominent nucleoli, and intranuclear pseudoinclusion. Cell block material demonstrated the trabeculae pattern of the malignant cells and Hep Par 1 immunopositivity. The final diagnosis of a metastatic cutaneous HCC was made. In conclusion, cutaneous HCC metastasis is rare and should be considered in the differential diagnosis in patients with a history of HCC presenting with suspicious skin lesion. In the right clinical setting, a confident diagnosis can be made in such cases by using the fine needle aspiration technique aided with immunopositivity for Hep Par 1 antibody of the aspirated material.

Matched MeSH terms: Biomarkers, Tumor/analysis*
Fulltext Ki-67 immuno-histochemistry index in stage III giant cell tumor of the bone

Ismail FW, Shamsudin AM, Wan Z, Daud SM, Samarendra MS

J Exp Clin Cancer Res, 2010 Mar 12;29(1):25.
PMID: 20226047 DOI: 10.1186/1756-9966-29-25

BACKGROUND: Giant cell tumor is an infrequent and unpredictable bony lesion. Although numerous attempts have been made to predict the behaviour of GCT, there are no definite biological or histological parameters to determine the prognosis or aggressiveness of this lesion
MATERIALS AND METHODS: We analyzed Ki 67 immuno-histochemistry of 31 consecutive cases staged III giant cell tumor to determine the clinico-pathological correlation. There were 19 male patients compare to 12 females. The mean age was 33.8 years ranged from 18 to 59 years. Five cases presented with local recurrence prior to wide resection and one case had multiple recurrences there after. Six cases had pulmonary metastases. Expression of Ki 67 antigen was evaluated by immuno-histochemical staining techniques using the avidin-biotin perioxidase complex method using an LSAB2 kit (Dako, Glostrup, Denmark). The primary antibody used in this study was Ki-67 (MIB-I clone, dilution 1:25; Dako).
RESULTS: The mean value of Ki-67 index obtained as a percentage of 1000 background cells was 8.15 (ranged 1.00 - 20.0). The median Ki 67 index was 7.5 with standard deviation of 5.12. The Ki 67 index of recurrence tumor was 4.323 compared to 6.05 without recurrence and was not statistically significant (mean difference of 0.865 with p value in independent t test of 0.736). The Ki 67 index was also not statistically significant in the presence of pulmonary metastases with the mean value of metastases group of 6.681 compared to 2.890 without metastases (mean difference of 1.895 with p value in independent t test of 0.424).
CONCLUSION: Ki 67 index is not use-full prognostic marker for aggressive type of giant cell tumor of the bone.

Matched MeSH terms: Biomarkers, Tumor/analysis*
Urine of patients with early prostate cancer contains lower levels of light chain fragments of inter-alpha-trypsin inhibitor and saposin B but increased expression of an inter-alpha-trypsin inhibitor heavy chain 4 fragment

Jayapalan JJ, Ng KL, Shuib AS, Razack AH, Hashim OH

Electrophoresis, 2013 Jun;34(11):1663-9.
PMID: 23417432 DOI: 10.1002/elps.201200583

The present study was aimed at the identification of proteins that are differentially expressed in the urine of patients with prostate cancer (PCa), those with benign prostatic hyperplasia (BPH) and age-matched healthy male control subjects. Using a combination of 2DE and MS/MS, significantly lower expression of urinary saposin B and two different fragments of inter-alpha-trypsin inhibitor light chain (ITIL) was demonstrated in the PCa patients compared to the controls. However, only one of the ITIL fragments was significantly different between the PCa and BPH patients. When image analysis was performed on urinary proteins that were transferred onto NC membranes and detected using a lectin that binds to O-glycans, a truncated fragment of inter-alpha-trypsin inhibitor heavy chain 4 was the sole protein found to be significantly enhanced in the PCa patients compared to the controls. Together, these urinary peptide fragments might be useful complementary biomarkers to indicate PCa as well as to distinguish it from BPH, although further epidemiological evidence on the specificity and sensitivity of the protein candidates is required.

Matched MeSH terms: Biomarkers, Tumor/analysis
Cytologic evaluation of prognostic markers in breast carcinoma

Jayaram G, Elsayed EM

Acta Cytol., 2005 Nov-Dec;49(6):605-10.
PMID: 16450899

To type breast carcinomaon on fine needle aspiration cytology (FNAC) material and correlate the results with histologic typing, to grade breast carcinoma on FNAC material and correlate the findings with Bloom-Richardson histologic grading, and to determine the estrogen receptor (ER) status in cases of breast carcinoma by immunocytochemical (ICC) staining of FNA cytologic material and correlate the findings with ER status, as determined by immunohistochemical (IHC) staining of tissue sections.

STUDY DESIGN: Seventy-seven cases of breast carcinoma diagnosed on FNAC formed the basis of this study. Typing was done in all cases on the basis of cytologic features and grading in 62. (Fifteen cases were special types of breast carcinoma). In all cases, ER status was determined by immunostaining of cytologic smears. Results of tumor typing, grading and ER status on cytologic material were compared with the results of histologic typing, grading and immunostaining of histologic material obtained from mastectomy or wide excision specimens.

RESULTS: Tumor typing was accurate in 73 of 77 cases (94.8%). Fifteen of 18 cases that were cytologically grade 3 were confirmed on histology, while 3 proved to be grade 2. Of 40 cytologic grade 2 cases, 26 were confirmed on histology, while 14 cases were grade 3. Three of 4 cytologically grade 1 cases were confirmed on histology while 1 was grade 2. The overall accuracy for cytologic grading was 71% (44 of 62 cases). Thirty-seven of 40 ER-positive cases (92.5%) were labeled ER positive on ICC. One case was ER negative on cytology, while in 2 cases the cellularity of the cytologic smear was insufficient to assess ER expression. Thirty-seven cases were negativefor ER on IHC. Nine of these showed ER positivity on ICC, 26 were negative, and 2 had cellularity that was inadequate for assessment of ER. Sensitivity and specificity rates for ER detection on ICC were 97.4% and 74.3%, respectively.

CONCLUSION: Tumor typing, grading and evaluation of ER status on FNA C material in breast carcinomas are simple, quick and moderately reliable techniques that compare and correlate favorably with histologic typing, grading and ER status on IHC.

Matched MeSH terms: Biomarkers, Tumor/analysis*
Malignant rhabdoid tumour of the kidney: report of a case showing focal glomeruloid differentiation

Jayaram G, Looi LM

Malays J Pathol, 1994 Jun;16(1):83-7.
PMID: 16329582

A five-month-old male baby presented with an abdominal mass which was found on computerised tomography (CT) to be involving the left kidney. Nephrectomy and histopathological study showed morphological featues of a malignant rhabdoid tumour. The tumour cells stained strongly for cytokeratin and epithelial membrane antigen and less intensely for vimentin. Electron microscopy revealed concentric whorled arrays of intermediate filaments within the tumour cell cytoplasm. The child was put on post-operative chemotherapy and radiotherapy but developed bilateral lung metastases and died three months after surgery.

Matched MeSH terms: Biomarkers, Tumor/analysis
Aberrant proteins featured in the saliva of habitual betel quid chewers: an indication of early oral premalignancy?

Jessie K, Jayapalan JJ, Rahim ZH, Hashim OH

Electrophoresis, 2014 Dec;35(24):3504-11.
PMID: 25223738 DOI: 10.1002/elps.201400252

Prolonged chewing of betel quid is known to cause oral diseases, including cancer. The present study was performed to screen for aberrant proteins in the saliva of habitual betel quid chewers compared to nonchewers. Saliva of female subjects (n = 10) who had been chewing betel quid for more than 20 years and nonbetel quid chewers (n = 10) of the same gender and range of age was analyzed by gel-based proteomics. Increased structural microheterogeneity of saliva haptoglobin beta chains indicated by shifts of focused spots similar to that earlier reported in patients with oral squamous cell carcinoma, and their relatively higher abundance compared to nonbetel quid chewers, were detected in saliva protein profiles of all chewers. In addition, the majority of the betel quid chewers also showed significant higher abundance of hemopexin, alpha-1B glycoprotein, alpha1-antitrypsin, complement C3, and transthyretin. These proteins had previously been associated with several different cancers. Our data demonstrated different forms of protein aberration in the saliva of betel quid chewers, which may be indicative of early oral precancerous conditions.

Matched MeSH terms: Biomarkers, Tumor/analysis*
CD10 expression pattern in prostatic adenocarcinoma: Elucidation of differences between Gleason's grades

Kaur M, Verma S, Gupta R, Pant L, Singh S

Malays J Pathol, 2018 Apr;40(1):57-60.
PMID: 29704385

CD10, a transmembrane endopeptidase, has been shown to be lost as an early event in prostate cancer. We aimed at evaluating the pattern of expression of CD10 in various Gleason's grades of prostatic adenocarcinoma in comparison with nodular hyperplasia of prostate. This retrospective study included 30 cases of nodular hyperplasia and 30 of prostatic adenocarcinoma of various Gleason's grades. Immunohistochemical staining for CD10 was performed on all cases and positivity evaluated as percentage of cells as well as location (membranous or cytoplasmic or both). Of prostatic adenocarcinomas, grade 3 was seen in 10 foci, grade 4 in 28 and grade 5 in 22 foci. CD10 positivity in carcinoma was lower than in nodular hyperplasia, with the lowest positivity in grade 5. The pattern of expression of CD10 also changed from membranous in grade 3 to cytoplasmic in grade 5. Loss of CD10 expression appears to be associated with increasing tumour grade in carcinoma prostate and this can potentially be useful in stratification of such patients.

Matched MeSH terms: Biomarkers, Tumor/analysis*
Fulltext Pattern of hMLH1, hMSH2 and hMSH6 expression and clinical characteristics in a sample of Malaysian colorectal carcinoma cases

Khoo JJ, Gunn A, Peh SC

Malays J Pathol, 2013 Jun;35(1):45-57.
PMID: 23817394 MyJurnal

Malignant transformation from normal colonic mucosa to carcinomas may be accelerated by genetic loss or inactivation of genes of the DNA mismatch repair system. The aim of the study was to determine the local incidence and pattern of immunohistochemical expression of mismatch repair proteins namely: hMLH1, hMSH2 and hMSH6 in a series of colorectal carcinomas (CRCs) and correlate this to their clinical and pathological features. Forty-three out of 298 cases of CRCs (14.4%) showed abnormal staining pattern for mismatch repair proteins with a majority (65.1%) showing single hMLH1 loss. Tumours with mismatch repair defect (MMR-d) were frequently found at the right side of colon (p<0.001), poorly differentiated carcinomas (p<0.001), produced more mucin (p=0.007), exophytic growth (p=0.007) and were bigger (p=0.002) than tumours with no mismatch repair defect. Immunohistochemical stains for mismatch repair proteins could be done in local laboratories on these selected cases before referring for the expensive molecular test.

Matched MeSH terms: Biomarkers, Tumor/analysis*
Fulltext Histomorphology and Immunohistochemistry of Gastrointestinal Stromal Tumors in a Malaysian Population

Kkrishnappa P, Loh EJ, Mohamad IB, Tata MD, Akhilesh M, Palayan K

Asian Pac J Cancer Prev, 2016;17(6):2795-9.
PMID: 27356692

PURPOSE: To study histomorphological and immunohistochemical patterns of gastro-intestinal stromal tumours (GISTs) in Malaysia.

MATERIALS AND METHODS: A total of 29 GIST cases from Hospital Tuanku Ja'afar, Seremban ,were studied retrospectively over a period of 10 years from January 2002 to December 2011. Patient demographic data like age, sex and etnicity were collected. Tumour characteristics like site, maximum dimension and specimen type were analysed. Evaluation was according to established criteria into very low, low, intermediate and high-risk categories. Immunohistochemical characteristics were also analysed.

RESULTS: The mean age of patients was 59.7 years. Males (59%) were found to be more commonly affected than females (41%). The Chinese (45%) were commonly affected than Malays (41%), and Indians (10%). The most common symptom was pain in the abdomen (13.8%). More than half of the cases were seen in stomach (53%). The tumour size ranged from 1.5 cm to 17 cm with a mean of 6.94cm. Microscopic findings revealed that the spindle cell type was the most common (76%). It was observed that the majority of the cases (48%) were categorised in the intermediate risk group. Immunohistochemical staining showed positivity for CD117 (78.6%), CD34 (71.4%), vimentin (86.2%), S-100 (27.6%), SMA (35.7%), PKC THETA (46.4%) and PDGRFA (67.9%).

Matched MeSH terms: Biomarkers, Tumor/analysis*
Human telomerase reverse transcriptase expression in oral carcinogenesis--a preliminary report

Kumar SK, Zain RB, Ismail SM, Cheong SC

J Exp Clin Cancer Res, 2005 Dec;24(4):639-46.
PMID: 16471328

Human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, is strongly associated with telomerase activity implicated in cellular immortalization and tumorigenesis. In situ detection of hTERT will aid in determining the localization of telomerase positive cells. The aim of this study was to detect hTERT protein expression in multistep oral carcinogenesis using paraffin embedded tissue samples, and to study the relationship of hTERT expression with different histological stages in oral carcinogenesis. Normal (n = 4), hyperplastic (n = 4), dysplastic (n = 4) and neoplastic (n = 10) oral epithelia representing different histological stages in oral carcinogenesis were included in the study. hTERT protein detection was done by immunohistochemistry (IHC) technique. Nuclear staining intensities were noted and the hTERT-labelling index was determined. Dysplastic and neoplastic oral epithelia showed an increased percentage of hTERT positive cells (Grade 4: > 50% positive staining nuclei) with intense staining in the basal, parabasal and superficial layers of the epithelia, unlike normal oral mucosa which showed intense staining only in the basal and parabasal cell layers, which are the normal proliferative progenitor compartments. hTERT protein expression was elevated with the corresponding advancement of the histological stages of oral carcinogenesis, from normal to hyperplasia to dysplasia to carcinoma. There seems to be an upregulation of hTERT protein expression during the progression of oral cancer, therefore, this may indicate the feasibility of IHC detection of hTERT protein in oral carcinogenesis as a potential diagnostic or prognostic marker.

Matched MeSH terms: Biomarkers, Tumor/analysis*
Stromal podoplanin expression and its clinicopathological role in breast carcinoma

Kumcu E, Unverdi H, Kaymaz E, Oral O, Turkbey D, Hucmenoglu S

Malays J Pathol, 2018 Aug;40(2):137-142.
PMID: 30173230

INTRODUCTION: Breast cancer is still a serious health problem in 21st century and diagnosis, treatment and prognosis of this malignant disease are subject to many research. While cancer research has been focused on tumour cells primarily, recent studies showed that tumour stroma contribute to carcinogenesis as well as tumour cells. Especially fibroblasts adjacent to epithelial tumour cells are not ordinary fibroblasts and play the critical role. Studies showed that these cancer associated fibroblasts (CAFs) have different genetic profile and protein expression. One of the differently expressed molecules recently found is podoplanin. Podoplanin, utilised as a lymphatic endothelial marker, is found to be expressed in CAFs. The aim of this study is to evaluate the relationship between the stromal expression of podoplanin in invasive breast carcinoma and clinicopathological parameters.
MATERIALS & METHODS: Podoplanin expression was evaluated immunohistochemically in 153 breast cancers. Tumours with ≥ 10% distinct cytoplasmic podoplanin staining in CAFs were considered as positive.
RESULTS: In 65.3% of analysed tumours, podoplanin expression was found positive in CAFs. According to our results, podoplanin positive CAFs correlated significantly with tumour size (p= 0.012), tumour grade (p= 0.032) and cerbB2 score (p= 0.032).
DISCUSSION: Our results suggest that podoplanin expression by CAFs could predict poor patient outcome in breast carcinoma.

Matched MeSH terms: Biomarkers, Tumor/analysis*
Spitz tumour with ALK rearrangement: A case report and literature review

Lai SK, Bakrin IH, Abd Rauf N, Abdul Raub SH

Malays J Pathol, 2024 Apr;46(1):103-108.
PMID: 38682850

Spitz tumour with ALK rearrangement is a recently described entity and a rare tumour. The incidence of Spitz tumour was estimated at 3.63 per 100,000 persons in American paediatric population; while there is no data in Asian population. Here we reported a case of an eleven-year-old Asian boy who presented with a left shin nodule of two months' duration. The skin biopsy revealed a Spitz tumour with predominantly spindle cell morphology arranged in fascicles, vertically orientated nests and radial growth pattern. Junctional component, melanin pigment or Kamino bodies were not identified. Immunohistochemical study displayed homogenous cytoplasmic staining for ALK. Fluorescence in-situ hybridisation (FISH) analysis confirmed ALK rearrangement. Review of the literatures demonstrated that positive ALK immunohistochemistry may not correlate with ALK rearrangement. ALK-rearranged Spitz tumour confirmed with FISH analysis favour clinically benign behaviour despite atypical histomorphology or positive sentinel lymph node. Therefore, correlation of histomorphology, immunohistochemical stain and molecular study are important for the definitive diagnosis of this entity.

Matched MeSH terms: Biomarkers, Tumor/analysis
Probing the endogenous peptidomes of cancer for biomarkers: A new endeavor

Lee PY, Low TY, Jamal R

Adv Clin Chem, 2018 12 27;88:67-89.
PMID: 30612607 DOI: 10.1016/bs.acc.2018.10.004

The life span of cancer patients can be prolonged with appropriate therapies if detected early. Mass screening for early detection of cancer, however, requires sensitive and specific biomarkers obtainable from body fluids such as blood or urine. To date, most biomarker discovery programs focus on the proteome rather than the endogenous peptidome. It has been long-established that tumor cells and stromal cells produce tumor resident proteases (TRPs) to remodel the surrounding tumor microenvironment in support of tumor progression. In fact, proteolytic products of TRPs have been shown to correlate with malignant behavior. Being of low molecular weight, these unique peptides can pass through the endothelial barrier of the vasculature into the bloodstream. As such, the cancer peptidome has increasingly become a focus for biomarker discovery. In this review, we discuss on the various aspects of the peptidome in cancer biomarker research.

Matched MeSH terms: Biomarkers, Tumor/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: Biomarkers, Tumor/analysis*
TRPM4 expression is associated with activated B cell subtype and poor survival in diffuse large B cell lymphoma

Loo SK, Ch'ng ES, Md Salleh MS, Banham AH, Pedersen LM, Møller MB, et al.

Histopathology, 2017 Jul;71(1):98-111.
PMID: 28248435 DOI: 10.1111/his.13204

AIMS: Transient receptor potential channel melastatin 4 (TRPM4) is an ion channel that regulates influx of calcium cations (Ca2+ ). Recent studies suggest that TRPM4 is an oncoprotein, and its up-regulated transcript level has been reported in diffuse large B cell lymphoma (DLBCL). We aimed to investigate TRPM4 protein expression pattern in non-malignant tissues and DLBCL cases, and its association with clinico-demographic parameters and survival in DLBCL.
METHODS AND RESULTS: Analysis of publicly available DLBCL microarray data sets showed that TRPM4 transcripts were up-regulated in DLBCL compared to normal germinal centre B (GCB) cells, were expressed more highly in the activated B cell-like DLBCL (ABC-DLBCL) subtype and higher TRPM4 transcripts conferred worse overall survival (OS) in R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)-treated DLBCL cases (P < 0.05). Our immunohistochemical analysis showed that TRPM4 was expressed in various human tissues but not in normal B cells within lymphoid tissues (reactive tonsil, lymph node and appendix). TRPM4 protein was present in 26% (n = 49 of 189) of our cohort of R-CHOP-treated DLBCL cases and this was associated significantly with more aggressive clinical parameters, including higher lactate dehydrogenase (LDH), Eastern Cooperative Oncology Group (ECOG) scores or stage (P < 0.01 for each of the parameters) and the ABC-DLBCL subtype (P = 0.016). TRPM4 positivity conferred significantly worse OS (P = 0.004) and progression-free survival (PFS) (P = 0.005). Worse OS remained associated significantly with TRPM4 positivity in multivariate analysis, including higher International Prognostic Index (IPI) or the non-GCB DLBCL phenotype (P < 0.05).
CONCLUSIONS: TRPM4 protein expression is up-regulated in DLBCL cases compared to non-malignant B cells with preferential expression in ABC-DLBCL cases, and it confers significantly poorer DLBCL patient outcomes.

Matched MeSH terms: Biomarkers, Tumor/analysis*
Using fuzzy association rule mining in cancer classification

Mahmoodian H, Hamiruce Marhaban M, Abdulrahim R, Rosli R, Saripan I

Australas Phys Eng Sci Med, 2011 Apr;34(1):41-54.
PMID: 21327594 DOI: 10.1007/s13246-011-0054-8

The classification of the cancer tumors based on gene expression profiles has been extensively studied in numbers of studies. A wide variety of cancer datasets have been implemented by the various methods of gene selection and classification to identify the behavior of the genes in tumors and find the relationships between them and outcome of diseases. Interpretability of the model, which is developed by fuzzy rules and linguistic variables in this study, has been rarely considered. In addition, creating a fuzzy classifier with high performance in classification that uses a subset of significant genes which have been selected by different types of gene selection methods is another goal of this study. A new algorithm has been developed to identify the fuzzy rules and significant genes based on fuzzy association rule mining. At first, different subset of genes which have been selected by different methods, were used to generate primary fuzzy classifiers separately and then proposed algorithm was implemented to mix the genes which have been associated in the primary classifiers and generate a new classifier. The results show that fuzzy classifier can classify the tumors with high performance while presenting the relationships between the genes by linguistic variables.

Matched MeSH terms: Biomarkers, Tumor/analysis*
Fulltext Human telomerase reverse transcriptase expression in ovarian tumors

Maraei AA, Hatta AZ, Shiran MS, Tan GC

Indian J Pathol Microbiol, 2012 Apr-Jun;55(2):187-91.
PMID: 22771641 DOI: 10.4103/0377-4929.97865

Ovarian cancer is the 6 th most common cancer among women. In ovarian tumors, the borderline category is not well defined due to the difficulty in assessing stromal invasion. The World Health Organization (WHO) defined it as tumor that lacks obvious invasion of the stroma with mitotic activity and nuclear abnormalities intermediate between clearly benign and unquestionably malignant. Telomerase is expressed in many human cancers and is hence a potential biomarker for cancer. Immunohistochemical study of anti-human telomerase enzyme reverse transcriptase (hTERT) antibody allows direct visualization of its expression. The aim of this study was to determine the expression of hTERT and serum CA-125 level in ovarian epithelial tumors, and their ability to distinguish borderline tumor from malignancy.

Matched MeSH terms: Biomarkers, Tumor/analysis*
Cyclooxygenase-2 (COX2) expression in adenocarcinoma surpasses that of squamous cell carcinoma in the uterine cervix

Marutha Muthu AK, Cheah PL, Koh CC, Chew MF, Toh YF, Looi LM

Malays J Pathol, 2017 Dec;39(3):251-255.
PMID: 29279587 MyJurnal

Over the years, adenocarcinoma (ADC), which has a worse prognosis than squamous cell carcinoma (SCC) of the cervix, has shown an increasing trend. Cyclooxygenase-2 (COX2) expression which has been associated with worse prognosis in several solid cancers was studied for its association with SCC and ADC of the cervix. 35 histologically re-confirmed SCC and 35 ADC were immunohistochemically stained for COX2 using a mouse monoclonal antibody to COX2 (1:100; Dako: Clone CX-294) on a Ventana Benchmark XT. The histoscore was computed as intensity of staining, semi-quantitated on a scale of 0-3 with 0 = negative, 1 = weak, 2 = moderate and 3 = strong staining intensity; multiplied by percentage of immunopositivity on a scale of 0-4 with 0 = <1%, 1 = 1-25%, 2 = 26-50%, 3 = 51-75% and 4 = ≥75% of immunopositive tumour cells. Histoscore 1-3/12 was considered as low and ≥4/12 as high COX2 expression. SCC affected Chinese more than Malays, while Malays had more ADC (p = 0.032). Mean age at presentation of SCC (57.5 years) was about a decade later than ADC at 47.9 years (p = 0.002). 30/35 (85.7%) of SCC and 34/35 (97.1%) of ADC expressed COX2. Histoscores of ADC (median = 4.0, IQR = 3.0-6.0) was significantly higher (p = 0.014) than those of SCC (median = 3.0, IQR = 2.0-3.0). High histoscores (≥4/12) were more frequent in ADC (55.9%) compared with SCC (26.7%) (p = 0.018), implicating COX2, either directly or indirectly, as a possible player in influencing the poorer outcome of ADC compared with SCC.

Matched MeSH terms: Biomarkers, Tumor/analysis*
BCL2 protein expression in follicular lymphomas with t(14;18) chromosomal translocations

Masir N, Campbell LJ, Goff LK, Jones M, Marafioti T, Cordell J, et al.

Br J Haematol, 2009 Mar;144(5):716-25.
PMID: 19120369 DOI: 10.1111/j.1365-2141.2008.07528.x

The t(14;18)(q32;q21) chromosomal translocation induces BCL2 protein overexpression in most follicular lymphomas. However the expression of BCL2 is not always homogeneous and may demonstrate a variable degree of heterogeneity. This study analysed BCL2 protein expression pattern in 33 cases of t(14;18)-positive follicular lymphomas using antibodies against two different epitopes (i.e. the widely used antibody BCL2/124 and an alternative antibody E17). 16/33 (49%) cases demonstrated strong BCL2 expression. In 10/33 (30%) cases, BCL2 expression was heterogeneous and in some of these, its loss appeared to be correlated with cell proliferation, as indicated by Ki67 expression. Double immunofluorescence labelling confirmed an inverse BCL2/Ki67 relationship, where in 24/28 (86%) cases cellular expression of BCL2 and Ki67 was mutually exclusive. In addition, seven BCL2 'pseudo-negative' cases were identified in which immunostaining was negative with antibody BCL2/124, but positive with antibody E17. Genomic DNA sequencing of these 'pseudo-negative' cases demonstrated eleven mutations in four cases and nine of these were missense mutations. It can be concluded that in follicular lymphomas, despite carrying the t(14;18) translocations, BCL2 protein expression may be heterogeneous and loss of BCL2 could be related to cell proliferation. Secondly, mutations in translocated BCL2 genes appear to be common and may cause BCL2 pseudo-negative immunostaining.

Matched MeSH terms: Biomarkers, Tumor/analysis*

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