Displaying publications 1 - 20 of 31 in total

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  1. Zhou X, Li Y, Wang W, Wang S, Hou J, Zhang A, et al.
    Theranostics, 2020;10(21):9443-9457.
    PMID: 32863938 DOI: 10.7150/thno.46078
    Objective: Esophageal squamous cell carcinoma (ESCC) is one of the most commonly diagnosed cancer types in China. Recent genomic sequencing analysis indicated the over-activation of Hippo/YAP signaling might play important roles for the carcinogenic process and progression for ESCC patients. However, little is known about the molecular mechanisms that controls Hippo signaling activity in ESCC. Our previous studies indicated that PLCE1-an important risk factor for ESCC-linked to ESCC progression through snail signaling, during this period, we found PARK2 was an important downstream target of PLCE1-snail axis. PARK2 was decreased in ESCC human samples, and correlated with good prognosis in ESCC patients. Further research showed that PARK2 could inhibit YAP, which functions as key downstream effectors of the Hippo pathway. Here, we aim to reveal the molecular mechanisms of PARK2 modulated Hippo pathway in ESCC. Methods: To evaluate the function of PARK2 in ESCC, we used a tissue microarray (TMA) of 223 human ESCC patients and immunohistochemistry to analyze the correlation between PARK2 expression and clinicopathologic variables. Depletion of endogenous PARK2 and YAP from ESCC cells using CRISPR/Cas9 technologies. Flow cytometry and EdU cell proliferation assay were used to detect proliferation of ESCC cells. Nude mice subcutaneous injection and Ki-67 staining were used to evaluate tumor growth in vivo. Migration and invasion assays were performed. In addition, lung metastasis models in mice were used to validate the function of PARK2 in vivo. Identification of PARK2 involved in hippo pathway was achieved by expression microarray screening, double immunofluorescence staining and co-immunoprecipitation assays. The RNA-seq analysis results were validated through quantitative real-time PCR (qRT-PCR) analysis. The protein half-life of YAP was analyzed by Cycloheximide assay, and the TEAD activity was detected by Luciferase reporter assays. Results: Clinical sample of ESCC revealed that low PARK2 expression correlated with late tumor stage (P < 0.001), poor differentiation (P < 0.04), lymph node (P < 0.001) and distant metastasis (P = 0.0087). Multivariate Cox proportional regression analysis further revealed that PARK2 expression (P = 0.032) is an independent prognostic factor for the overall survival of ESCC patients. Besides, the immunohistochemistry results showed that PARK2 negatively correlated with YAP protein level (P < 0.001). PARK2 depletion promotes ESCC progression both through Hippo/YAP axis, while PARK2 overexpression suppresses ESCC tumor progression by Hippo signaling. Co-IP and ubiquitination assays revealed that PARK2 could interact with YAP in the cytosol and promotes YAP K48-linked ubiquitination at K90 sites. Conclusion: Clinical sample analysis and mechanistic study have validated PARK2 as a tumor suppressor for ESCC. Multivariate Cox proportional regression analysis further revealed that PARK2 is an independent prognostic factor for the overall survival of ESCC patients. Cellular and molecular mechanisms in this study showed that PARK2 associated with YAP protein in the cytosol, promoted YAP ubiquitination and proteasome-dependent degradation in ESCC cells. Therefore, as a novel modulator for Hippo signaling, modulation of PARK2 activity or gene expression level could be an appealing strategy to treat esophageal.
    Matched MeSH terms: Immunohistochemistry/methods
  2. Tay TKY, Lim KL, Hilmy MH, Thike AA, Goh ST, Song LH, et al.
    Malays J Pathol, 2017 Dec;39(3):257-265.
    PMID: 29279588
    INTRODUCTION: Human papillomavirus (HPV) testing is used as a means of triaging cervico-vaginal smears with low grade squamous abnormalities or as part of co-testing with cytology. While HPV testing has a high sensitivity, it has a low specificity in detecting cervical intraepithelial neoplasia grade 2 and above (CIN 2+) leading to unnecessary colposcopy referrals. We investigate the accuracy of the p16/Ki-67 dual immunocytochemical stain in determining the presence of CIN 2+ lesions on histology and its potential as a superior biomarker for triage.

    METHODS: Liquid based cervico-vaginal cytology specimens with squamous abnormalities and corresponding histology from 97 women with subsequent colposcopy and biopsy were included. The specimens were then subjected to the dual stain and Roche Cobas 4800 multiplex real time PCR HPV DNA testing. The sensitivity and specificity of the dual stain and HPV testing were calculated using CIN 2+ on histology as a reference standard.

    RESULTS: The sensitivity and specificity of the dual stain in detecting histology proven CIN 2+ was 93.7% and 76.5% while HPV testing was 85.7% and 14.7% respectively. Of the 44 women with ASCUS or LSIL on cytology, the dual stain also reduced the number of unnecessary colposcopy referrals from 27 to 7 when used as a triage marker compared to HPV testing.

    CONCLUSION: p16/Ki-67 dual stain was more sensitive and specific than HPV testing in determining the presence of CIN 2+ on histology. It could triage low grade cervico-vaginal specimens more effectively and potentially help women avoid unnecessary colposcopies. Future studies are needed to further evaluate its role in cervical cancer screening programmes.

    Matched MeSH terms: Immunohistochemistry/methods
  3. Ch'ng ES, Khiro FI
    Malays J Pathol, 2018 Aug;40(2):209-211.
    PMID: 30173241
    No abstract available.
    Matched MeSH terms: Immunohistochemistry/methods*
  4. Palo S, Biligi DS
    Malays J Pathol, 2017 Apr;39(1):55-67.
    PMID: 28413206
    OBJECTIVE: Due several overlapping histomorphological features and pitfalls in thyroid pathology, there is need to establish a panel of immunomarkers that would aid in proper diagnosis. This study was carried out to investigate the ability of HBME-1, CK19, and S100 in differentiating between hyperplastic, benign and malignant thyroid lesions.

    MATERIALS AND METHODS: Immunohistochemical analysis of 60 thyroidectomy specimens (10 hyperplastic nodules, 14 follicular adenomas and 36 malignant thyroid neoplasms) was carried out. The extent and intensity of HBME-1, CK19, and S100 immunoreactivity was assessed in each case.

    RESULTS: HBME-1 positivity was noted in 86.1% of malignant cases while the majority of the benign lesions were negative. Diffuse strong CK19 positivity was documented in 27/31 papillary carcinoma whereas all cases of follicular carcinoma and medullary carcinoma were negative. Most of the hyperplastic nodules and follicular adenomas were also CK19 negative, although focal weak staining was noted in a few cases. S100 was positive only in medullary carcinoma. HBME-1 was most sensitive (86.1%) and specific (87.5%) in distinguishing between benign and malignant thyroid lesions. The diagnostic accuracy was further increased when HBME-1 was used simultaneously with CK19/S100/CK19+S100. The sequential use of HBME-1 and CK19 also proved beneficial in discriminating between the various follicular-patterned thyroid lesions.

    CONCLUSION: HBME-1 immunolabeling suggests malignancy, whereas strong diffuse CK19 positivity substantiates papillary differentiation. The utilization of these markers (alone or in combination) along with histomorphological evaluation is helpful in the differential diagnosis. S100 has minimal utility in this regard.

    Matched MeSH terms: Immunohistochemistry/methods
  5. Teoh SH, Khoo JJ, Abdul Salam DSD, Peh SC, Cheah SC
    Malays J Pathol, 2019 Dec;41(3):273-281.
    PMID: 31901912
    INTRODUCTION: Epstein-Barr Virus (EBV) is associated with several B-cell non-Hodgkin's lymphoma (NHL), but the role of EBV in diffuse large B-cell lymphoma (DLBCL) is poorly defined. Several studies indicated the expression of phosphorylated STAT3 (pSTAT3) is predominant in EBV(+)- DLBCL, of which its activated form can promote the downstream oncogenes expression such as c-MYC. c-MYC gene rearrangements are frequently found in aggressive lymphoma with inferior prognosis. Furthermore, EBV is a co-factor of MYC dysregulation. JAK1/STAT3 could be the downstream pathway of EBV and deregulates MYC. To confirm the involvement of EBV in JAK1/ STAT3 activation and MYC deregulation, association of EBV, pSTAT3 and MYC in EBV(+)- DLBCL cases were studied. The presence of pSTAT3 and its upstream proteins: pJAK1 is identify to delineate the role of EBV in JAK1/STAT3 pathway.

    MATERIALS AND METHODS: 51 cases of DLBCL paraffin-embedded tissue samples were retrieved from a single private hospital in Kuala Lumpur, Malaysia. EBER-ISH was performed to identify the EBV expression; ten EBV(+)-DLBCL cases subjected to immunohistochemistry for LMP1, pJAK1, pSTAT3 and MYC; FISH assay for c-MYC gene rearrangement.

    RESULTS: Among 10 cases of EBV(+)-DLBCL, 90% were non-GCB subtype (p=0.011), 88.9% expressed LMP1. 40% EBV(+)-DLBCL had pJAK1 expression.

    CONCLUSION: 66.7% EBV(+)-DLBCL showed the positivity of pSTAT3, which implies the involvement of EBV in constitutive JAK/STAT pathway. 44.5% EBV(+)-DLBCL have co-expression of pSTAT3 and MYC, but all EBV(+)-DLBCL was absence with c-MYC gene rearrangement. The finding of clinical samples might shed lights to the lymphomagenesis of EBV associated with non-GCB subtypes, and the potential therapy for pSTAT3-mediated pathway.

    Matched MeSH terms: Immunohistochemistry/methods
  6. Wa Kammal WS, Yahaya A, Shah SA, Abdullah Suhaimi SN, Mahasin M, Mustangin M, et al.
    Malays J Pathol, 2019 Dec;41(3):293-301.
    PMID: 31901914
    INTRODUCTION: Thyroid carcinoma is classically diagnosed based on certain histological criteria. In some cases, definitive diagnoses may be challenging when morphological features are equivocal. This study evaluated the usefulness of Cytokeratin 19 (CK 19) as an immunohistochemical marker to differentiate the different histological types of malignant thyroid neoplasms, particularly papillary thyroid carcinoma (PTC) from benign thyroid lesions.

    MATERIALS AND METHODS: We collected 54 malignant and 65 benign thyroid lesions diagnosed by histology in Universiti Kebangsaan Malaysia Medical Centre between January 2010 and December 2015. All cases were immunohistochemically stained with CK 19 and evaluated by 3 independent observers. The immunostaining patterns were scored based on the intensity and proportion of staining and finally graded as negative, weak positive, moderate positive or strong positive. In addition, the immunostaining scores of the malignant cases were correlated with their TNM pathological tumour stages.

    RESULTS: Cytokeratin 19 staining expression was higher in malignant than benign thyroid lesions (p < 0.001) which was most prominent among classical PTC. The four PTC cases that showed negative or weak staining were all follicular variant of PTC. Benign conditions were mostly negative or showed weak positivity. There was no correlation between CK 19 expression and TNM primary tumour stage (pT).

    CONCLUSION: Cytokeratin 19 is a useful marker in differentiating malignant from benign thyroid conditions particularly the classical PTC, provided its interpretation is by correlation with morphology and takes into consideration the intensity and proportion of positive staining.

    Matched MeSH terms: Immunohistochemistry/methods
  7. Ngan KW, Shaari S, Subramaniam T
    Singapore Med J, 2009 Sep;50(9):e329-31.
    PMID: 19787163
    We report a six-year-old Malay girl who presented with a right retroperitoneal tumour that measured 7.5 cm in diameter. A wide excision of the lesion was performed. The tumour was separated from a normal-appearing right kidney by a capsule. Microscopically, this well-encapsulated tumour was composed of classical triphasic components: epithelial, mesenchymal and blastemal areas. The immunohistochemical study showed WT1 expression in the blastemal area. Thus, a diagnosis of Wilms' tumour with favourable histology was made. The patient was well for 12 months. Extrarenal Wilms' tumour is uncommon, with the majority of cases occurring in the retroperitoneal and inguinal areas. Wilms' tumour that is not arising from the intrarenal area but shares a common capsule with the ipsilateral kidney, is even rarer. Indeed, our case would be more appropriately classified as juxtarenal/pararenal Wilms' tumour. Despite its rarity, an extrarenal or even juxtarenal/pararenal Wilms' tumour should be included in the differential diagnosis of retroperitoneal tumour.
    Matched MeSH terms: Immunohistochemistry/methods
  8. Mathieu C, Guillaume V, Sabine A, Ong KC, Wong KT, Legras-Lachuer C, et al.
    PLoS One, 2012;7(2):e32157.
    PMID: 22393386 DOI: 10.1371/journal.pone.0032157
    Nipah virus (NiV) is a recently emerged zoonotic Paramyxovirus that causes regular outbreaks in East Asia with mortality rate exceeding 75%. Major cellular targets of NiV infection are endothelial cells and neurons. To better understand virus-host interaction, we analyzed the transcriptome profile of NiV infection in primary human umbilical vein endothelial cells. We further assessed some of the obtained results by in vitro and in vivo methods in a hamster model and in brain samples from NiV-infected patients. We found that NiV infection strongly induces genes involved in interferon response in endothelial cells. Among the top ten upregulated genes, we identified the chemokine CXCL10 (interferon-induced protein 10, IP-10), an important chemoattractant involved in the generation of inflammatory immune response and neurotoxicity. In NiV-infected hamsters, which develop pathology similar to what is seen in humans, expression of CXCL10 mRNA was induced in different organs with kinetics that followed NiV replication. Finally, we showed intense staining for CXCL10 in the brain of patients who succumbed to lethal NiV infection during the outbreak in Malaysia, confirming induction of this chemokine in fatal human infections. This study sheds new light on NiV pathogenesis, indicating the role of CXCL10 during the course of infection and suggests that this chemokine may serve as a potential new marker for lethal NiV encephalitis.
    Matched MeSH terms: Immunohistochemistry/methods
  9. Niazi MKK, Abas FS, Senaras C, Pennell M, Sahiner B, Chen W, et al.
    PLoS One, 2018;13(5):e0196547.
    PMID: 29746503 DOI: 10.1371/journal.pone.0196547
    Automatic and accurate detection of positive and negative nuclei from images of immunostained tissue biopsies is critical to the success of digital pathology. The evaluation of most nuclei detection algorithms relies on manually generated ground truth prepared by pathologists, which is unfortunately time-consuming and suffers from inter-pathologist variability. In this work, we developed a digital immunohistochemistry (IHC) phantom that can be used for evaluating computer algorithms for enumeration of IHC positive cells. Our phantom development consists of two main steps, 1) extraction of the individual as well as nuclei clumps of both positive and negative nuclei from real WSI images, and 2) systematic placement of the extracted nuclei clumps on an image canvas. The resulting images are visually similar to the original tissue images. We created a set of 42 images with different concentrations of positive and negative nuclei. These images were evaluated by four board certified pathologists in the task of estimating the ratio of positive to total number of nuclei. The resulting concordance correlation coefficients (CCC) between the pathologist and the true ratio range from 0.86 to 0.95 (point estimates). The same ratio was also computed by an automated computer algorithm, which yielded a CCC value of 0.99. Reading the phantom data with known ground truth, the human readers show substantial variability and lower average performance than the computer algorithm in terms of CCC. This shows the limitation of using a human reader panel to establish a reference standard for the evaluation of computer algorithms, thereby highlighting the usefulness of the phantom developed in this work. Using our phantom images, we further developed a function that can approximate the true ratio from the area of the positive and negative nuclei, hence avoiding the need to detect individual nuclei. The predicted ratios of 10 held-out images using the function (trained on 32 images) are within ±2.68% of the true ratio. Moreover, we also report the evaluation of a computerized image analysis method on the synthetic tissue dataset.
    Matched MeSH terms: Immunohistochemistry/methods*
  10. Ng KL, Del Vecchio SJ, Samaratunga H, Morais C, Rajandram R, Vesey DA, et al.
    Pathology, 2018 Aug;50(5):504-510.
    PMID: 29970253 DOI: 10.1016/j.pathol.2018.01.007
    One of the challenges in differentiating chromophobe renal cell carcinoma (chRCC) from benign renal oncocytoma (RO) is overlapping morphology between the two subtypes. The aim of this study was to investigate the usefulness of expression of leptin (Ob) and its receptor (ObR) in discriminating chRCC from RO. Sections from paraffin-embedded, formalin-fixed tumour nephrectomy specimens of 45 patients, made up of 30 chRCC (15 eosinophilic variant and 15 non-eosinophilic variant) and 15 RO, were used in this study. Samples (30) of clear cell RCC (ccRCC), the most common histological subtype, were used to verify staining patterns found by others in our cohort of Australasian patients. Matched morphologically normal non-cancer kidney tissues were included for each specimen. Sections were batch-immunostained using antibodies against Ob and ObR. Stained sections were digitally scanned using Aperio ImageScope, and the expression pattern of Ob and ObR was studied. In this cohort, male to female ratio was 2:1; median age was 64 (45-88 years); and median tumour size was 3.8 cm (range 1.2-18 cm). There were 47 (62.7%) T1, seven T2, 20 T3 and one T4 stage RCC. Two patients with ccRCC presented with metastases. Nuclear expression of Ob was significantly higher in RO compared with chRCC. The increased nuclear expression of Ob in RO compared with chRCC may be a useful aid in the difficult histological differentiation of RO from chRCC, especially eosinophilic variants of chRCC.
    Matched MeSH terms: Immunohistochemistry/methods
  11. Eamsobhana P, Tungtrongchitr A, Yong HS, Prasartvit A, Wanachiwanawin D, Gan XX
    Parasitology, 2021 Feb;148(2):234-239.
    PMID: 33004092 DOI: 10.1017/S0031182020001894
    Serological tests may yield false-negative results for specific antibodies detection before or at the early seroconversion phase. Tests that detect circulating antigens of Angiostrongylus cantonensis would therefore be of value in diagnosis to distinguish current or past infection. Here, a quick, easy to perform, portable and inexpensive diagnostic device for detection of 31-kDa A. cantonensis specific antigens had been developed. This sandwich dot-immunogold filtration assay (AcDIGFAAg), for detecting active angiostrongyliasis was produced using anti-A. cantonensis polyclonal antibody dotted on the nitrocellulose membrane as a capture agent and colloidal gold-labelled anti-31 kDa A. cantonensis antibody as a detection agent. A well-defined pink dot, indicating positivity, was seen readily by naked eye within 10-15 min. The AcDIGFAAg detected A. cantonensis-specific antigens in cerebrospinal fluid samples from 4 out of 10 serologically confirmed angiostrongyliasis cases and 2 out of 5 suspected cases with negative anti-A. cantonensis antibodies. Among the 19 patient sera with A. cantonensis infection, 2 showed positive reaction by AcDIGFAAg. No positive AcDIGFAAg reaction was observed in all the serum samples with other parasitic diseases, and the healthy controls. The present 'AcDIGFAAg' enables rapid qualitative detection of the specific 31-kDa antigens of A. cantonensis in clinical samples with potential for application even under resource-limited settings.
    Matched MeSH terms: Immunohistochemistry/methods*
  12. Eamsobhana P, Gan XX, Ma A, Wang Y, Wanachiwanawin D, Yong HS
    J Helminthol, 2014 Dec;88(4):396-401.
    PMID: 23710755 DOI: 10.1017/S0022149X13000321
    A rapid dot immunogold filtration assay (DIGFA) was adopted for specific immunodiagnosis of human cerebral angiostrongyliasis, using purified 31-kDa glycoprotein specific to Angiostrongylus cantonensis as diagnostic antigen and protein A colloidal gold conjugate as antigen-antibody detector. A total of 59 serum samples were assayed - 11 samples from clinically diagnosed patients with detectable A. cantonensis-specific antibody in immunoblotting; 23 samples from patients with other related parasitic diseases, i.e. gnathostomiasis (n= 8), cysticercosis (n= 5), toxocariasis (n= 2), filariasis (n= 4), paragonimiasis (n= 2) and malaria (n= 2); and 25 samples from normal healthy subjects. The sensitivity and specificity of DIGFA to detect anti-A. cantonensis specific antibodies in serologically confirmed angiostrongyliasis cases, were both 100%. No positive DIGFA was observed in cases with other parasitic diseases, and the healthy control subjects. The 3-min DIGFA is as sensitive and specific as the 3-h immunoblot test in angiostrongyliasis confirmed cases that revealed a 31-kDa reactive band. The gold-based DIGFA is more rapid and easier to perform than the traditional enzyme-linked immunosorbent assay (ELISA). The test utilizing purified A. cantonensis antigen is reliable and reproducible for specific immunodiagnosis of human infection with A. cantonensis - thus can be applied as an additional routine test for clinical diagnostic support. Large-scale sero-epidemiological studies in endemic communities in north-east Thailand are under way to evaluate its usefulness under field conditions.
    Matched MeSH terms: Immunohistochemistry/methods*
  13. Rashid Ali MR, Kannan KK
    J Bronchology Interv Pulmonol, 2015 Jan;22(1):66-8.
    PMID: 25590487 DOI: 10.1097/LBR.0000000000000128
    We report a case of a 52-year-old patient who had undergone a bladder resection and an ileal conduit for a transitional cell carcinoma. He then presented with a short history of hemoptysis 3 months later. Rigid bronchoscopy was performed revealing an endobronchial lesion, which was removed via laser and debulking method without complications. Histopathologic examination confirmed it to be a benign endobronchial glomus tumor. On the basis of our literature search, this is the 34th reported case of glomus tumor arising from the respiratory tract, seventh reported case of an endobronchial glomus tumor treated bronchoscopically, and the first possibly coincidental finding in relation to a patient with primary transitional bladder cell carcinoma.
    Matched MeSH terms: Immunohistochemistry/methods
  14. 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: Immunohistochemistry/methods
  15. Tan GC, Norlatiffah S, Sharifah NA, Razmin G, Shiran MS, Hatta AZ, et al.
    Indian J Pathol Microbiol, 2010 Jan-Mar;53(1):1-6.
    PMID: 20090212 DOI: 10.4103/0377-4929.59173
    Cervical cancer is the second most common cancer affecting Malaysian women. Despite the implementation of pap smear screening, many women are still diagnosed only in the advanced stage of cervical cancer. This could partly be due to failure of detection of its precursor lesions; hence the need to search for novel biomarkers to assist in the screening and diagnosis of cervical neoplasia. This study aims to determine the expression of p16INK4A and survivin as possible predictive biomarkers in cervical squamous neoplasm.
    Matched MeSH terms: Immunohistochemistry/methods
  16. Md Pauzi SH, Masir N, Yahaya A, Mohammed F, Tizen Laim NMS, Mustangin M, et al.
    Indian J Pathol Microbiol, 2021 10 22;64(4):677-682.
    PMID: 34673585 DOI: 10.4103/IJPM.IJPM_983_20
    Background: Human epidermal growth factor receptor 2 (HER2) over-expression in breast cancer is associated with aggressive tumor behavior and predicts response to targeted therapy. Accurate HER2 result is paramount for optimal patient management. However, routine HER2 immunohistochemistry (IHC) testing are subjected to intra- and inter-laboratory variability.

    Objective: This study aims to determine inter-laboratory variation in HER2 IHC testing through a slide-exchange program between five main reference laboratories.

    Method: A total of 20 breast carcinoma cases with different known HER2 expression and gene status were selected by the central laboratory in five testing rounds. Three unstained tissue sections from each case were sent to participating laboratories, which immunostained and interpreted the HER2 immunohistochemistry result. One of the stained slides was sent to one designated participating laboratory for evaluation. Results were analyzed by the central laboratory.

    Results: A complete concordance was achieved in six IHC-positive and six IHC-negative cases, its gene status of which was confirmed by in-situ-hybridization (ISH) study. The discordant results were observed in six equivocal cases, one negative case and one positive case with a concordance rate of 50-88.3%. Interestingly, the negative discordant case actually displays tumor heterogeneity. Good inter-observer agreement was achieved for all participating laboratories (k = 0.713-1.0).

    Conclusion: Standardization of HER2 testing method is important to achieve optimum inter-laboratory concordance. Discordant results were seen mainly in equivocal cases. Intra-tumoral heterogeneity may impact the final HER2 IHC scoring. The continuous quality evaluation is therefore paramount to achieve reliable HER2 results.

    Matched MeSH terms: Immunohistochemistry/methods
  17. Bukari BA, Citartan M, Ch'ng ES, Bilibana MP, Rozhdestvensky T, Tang TH
    Histochem Cell Biol, 2017 May;147(5):545-553.
    PMID: 28321500 DOI: 10.1007/s00418-017-1561-9
    Antibodies have been the workhorse for diagnostic immunohistochemistry to specifically interrogate the expression of certain protein to aid in histopathological diagnosis. This review introduces another dimension of histochemistry that employs aptamers as the core tool, the so-called aptahistochemistry. Aptamers are an emerging class of molecular recognition elements that could recapitulate the roles of antibodies. The many advantageous properties of aptamers suited for this diagnostic platform are scrutinized. An in-depth discussion on the technical aspects of aptahistochemistry is provided with close step-by-step comparison to the more familiarized immunohistochemical procedures, namely functionalization of the aptamer as a probe, antigen retrieval, optimization with emphasis on incubation parameters and visualization methods. This review offers rationales to overcome the anticipated challenges in transition from immunohistochemistry to aptahistochemistry, which is deemed feasible for an average diagnostic pathology laboratory.
    Matched MeSH terms: Immunohistochemistry/methods*
  18. 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: Immunohistochemistry/methods*
  19. Tamin A, Rota PA
    Dev Biol (Basel), 2013;135:139-45.
    PMID: 23689891 DOI: 10.1159/000189236
    Hendra virus (HeV) and Nipah virus (NiV) are the causative agents of emerging transboundary animal disease in pigs and horses. They also cause fatal disease in humans. NiV has a case fatality rate of 40 - 100%. In the initial NiV outbreak in Malaysia in 1999, about 1.1 million pigs had to be culled. The economic impact was estimated to be approximately US$450 million. Worldwide, HeV has caused more than 60 deaths in horses with 7 human cases and 4 deaths. Since the initial outbreak, HeV spillovers from Pteropus bats to horses and humans continue. This article presents a brief review on the currently available diagnostic methods for henipavirus infections, including advances achieved since the initial outbreak, and a gap analysis of areas needing improvement.
    Matched MeSH terms: Immunohistochemistry/methods
  20. Abas FS, Shana'ah A, Christian B, Hasserjian R, Louissaint A, Pennell M, et al.
    Cytometry A, 2017 06;91(6):609-621.
    PMID: 28110507 DOI: 10.1002/cyto.a.23049
    The advance of high resolution digital scans of pathology slides allowed development of computer based image analysis algorithms that may help pathologists in IHC stains quantification. While very promising, these methods require further refinement before they are implemented in routine clinical setting. Particularly critical is to evaluate algorithm performance in a setting similar to current clinical practice. In this article, we present a pilot study that evaluates the use of a computerized cell quantification method in the clinical estimation of CD3 positive (CD3+) T cells in follicular lymphoma (FL). Our goal is to demonstrate the degree to which computerized quantification is comparable to the practice of estimation by a panel of expert pathologists. The computerized quantification method uses entropy based histogram thresholding to separate brown (CD3+) and blue (CD3-) regions after a color space transformation. A panel of four board-certified hematopathologists evaluated a database of 20 FL images using two different reading methods: visual estimation and manual marking of each CD3+ cell in the images. These image data and the readings provided a reference standard and the range of variability among readers. Sensitivity and specificity measures of the computer's segmentation of CD3+ and CD- T cell are recorded. For all four pathologists, mean sensitivity and specificity measures are 90.97 and 88.38%, respectively. The computerized quantification method agrees more with the manual cell marking as compared to the visual estimations. Statistical comparison between the computerized quantification method and the pathologist readings demonstrated good agreement with correlation coefficient values of 0.81 and 0.96 in terms of Lin's concordance correlation and Spearman's correlation coefficient, respectively. These values are higher than most of those calculated among the pathologists. In the future, the computerized quantification method may be used to investigate the relationship between the overall architectural pattern (i.e., interfollicular vs. follicular) and outcome measures (e.g., overall survival, and time to treatment). © 2017 International Society for Advancement of Cytometry.
    Matched MeSH terms: Immunohistochemistry/methods
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