Displaying publications 1 - 20 of 31 in total

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  1. 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
  2. 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
  3. Chai WL, Moharamzadeh K, Brook IM, Van Noort R
    Biotech Histochem, 2011 Aug;86(4):242-54.
    PMID: 20392135 DOI: 10.3109/10520291003707916
    The success of dental implant treatment depends on the healing of both hard and soft tissues. While osseointegration provides initial success, the biological seal of the peri-implant soft tissue is crucial for maintaining the long term success of implants. Most studies of the biological seal of peri-implant tissues are based on animal or monolayer cell culture models. To understand the mechanisms of soft tissue attachment and the factors affecting the integrity of the soft tissue around the implants, it is essential to obtain good quality histological sections for microscopic examination. The nature of the specimens, however, which consist of both metal implant and soft peri-implant tissues, poses difficulties in preparing the specimens for histomorphometric analysis of the implant-soft tissue interface. We review various methods that have been used for the implant-tissue interface investigation with particular focus on the soft tissue. The different methods are classified and the advantages and limitations of the different techniques are highlighted.
    Matched MeSH terms: Immunohistochemistry/methods*
  4. Abu Backer FM, Mustapha NR, Othman NH
    Anal. Quant. Cytol. Histol., 2011 Oct;33(5):283-8.
    PMID: 22611756
    To differentiate endocervical adenocarcinoma (ECA) from endometrial adenocarcinoma (EMA) using p16INK4a, p21WAF1 and p27Kip1.
    Matched MeSH terms: Immunohistochemistry/methods
  5. Azrif M, Ibrahim J, Aslan NM, Fong KV, Ismail F
    Asian Pac J Cancer Prev, 2011;12(1):157-62.
    PMID: 21517250
    INTRODUCTION: Neoadjuvant chemotherapy for locally advanced breast cancer is given with the aim of shrinking the disease sufficiently for surgery. However, many clinical trials investigating neoadjuvant chemotherapy regimens were conducted for operable breast cancer.

    METHODS AND MATERIALS: Patients with T3-4, N2 M0 breast cancer diagnosed between January 2005 and December 2008 and who received at least one cycle of neoadjuvant chemotherapy were eligible for this study. Thirty-four patients were identified from the Chemotherapy Daycare Records and their medical records were reviewed retrospectively. The neoadjuvant chemotherapy regimen administered was at the discretion of the treating oncologist. Breast tumour size and nodal status was assessed at diagnosis, at each cycle and before surgery.

    RESULTS: All 34 patients had invasive ductal cancer. The median age was 52 years (range 27-69). 65% had T4 disease and 76% were clinically lymph node positive at diagnosis. The median size of the breast tumour at presentation was 80 mm (range 42-200 mm). Estrogen and progesterone receptor positivity was seen in less than 40% and HER2 positivity, by immunohistochemistry, in 27%. The majority (85%) of patients had anthracycline based chemotherapy, without taxanes. The overall response rate (clinical CR+PR) was 67.6% and pathological complete responses were apparent in two (5.9%). 17.6% of patients defaulted part of their planned treatment. Recurrent disease was seen in 44.1% and the median time to relapse was 11.3 months. The three year disease free and overall survival rates were 52.5% and 58% respectively.

    CONCLUSION: Neoadjuvant chemotherapy for locally advanced breast cancer in a Malaysian setting confers response and pCR rates comparable to published clinical trials. Patients undergoing neoadjuvant chemotherapy are at risk of defaulting part of their treatment and therefore their concerns need to be identified proactively and addressed in order to improve outcomes.

    Matched MeSH terms: Immunohistochemistry/methods
  6. Heah KG, Hassan MI, Huat SC
    Asian Pac J Cancer Prev, 2011;12(4):1017-22.
    PMID: 21790244
    INTRODUCTION: Oral squamous cell carcinoma (OSCC) has high local recurrence, partly caused by the lack of clear margin identification on surgical removal of cancerous tissues. Direct visualization by immunostaining and fluorescent in situ hybridization (FISH) in tissue sections gives more definite information about genetic damage at margins with appropriately selected biomarkers.

    AIMS: To determine the usefulness of immunohistochemical techniques and FISH of the tumour suppressor TP 53 gene to identify microinvasion in marginal tissue sections and to relate the possible correlation between protein expression and genetic aberrations in OSCC cases in Malaysia.

    METHODS: Immunohistochemistry and FISH of TP 53 genes were applied on 26 OSCC formalin fixed paraffin embed (FFEP) blocks selected from two oral cancer referral centers in Malaysia.

    RESULTS: For p53 protein immunohistochemistry, 96% of the 26 OSCC studied showed positive immunostaining at the excision margins. In FISH assay, 48.9±9.7% of the cancerous cells were monoploid for p53 probe signals, 41.0±9.5 % were diploid, and 10.2±7.8 % were polyploid. A correlation between p53 immunostaining and TP53 gene aberrations was noted (p< 0.05).

    CONCLUSIONS: Immunohistochemical analysis of p53 protein expression and FISH of TP53 gene could be applied as screening tool for microinvasion of OSCC.

    Matched MeSH terms: Immunohistochemistry/methods
  7. Ning TZ, Kin WW, Mustafa S, Ahmed A, Noordin R, Cheong TG, et al.
    Asian Pac J Trop Biomed, 2012 Jan;2(1):61-5.
    PMID: 23569836 DOI: 10.1016/S2221-1691(11)60191-3
    To compare the efficacy of three different tissue stains, namely haematoxylin and eosin (H&E), periodic-acid Schiff (PAS) and immunohistochemical (IHC) stains for detection of Entamoeba histolytica (E. histolytica) trophozoites in abscessed liver tissues of hamster.
    Matched MeSH terms: Immunohistochemistry/methods
  8. 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*
  9. 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
  10. 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
  11. 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
  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. Wong YP, Shah SA, Shaari N, Mohamad Esa MS, Sagap I, Isa NM
    Asian Pac J Cancer Prev, 2014;15(4):1725-30.
    PMID: 24641399
    Management of patients with stage II colorectal carcinomas remains challenging as 20 - 30% of them will develop recurrence. It is postulated that these patients may harbour nodal micrometastases which are imperceptible by routine histopathological evaluation. The aims of our study were to evaluate (1) the feasibility of multilevel sectioning method utilizing haematoxylin and eosin stain and immunohistochemistry technique with cytokeratin AE1/AE3, in detecting micrometastases in histologically-negative lymph nodes, and (2) correlation between nodal micrometastases with clinicopathological parameters. Sixty two stage I and II cases with a total of 635 lymph nodes were reviewed. Five-level haematoxylin and eosin staining and one-level cytokeratin AE1/AE3 immunostaining were performed on all lymph nodes retrieved. The findings were correlated with clinicopathological parameters. Two (3.2%) lymph nodes in two patients (one in each) were found to harbour micrometastases detected by both methods. With cytokeratin AE1/AE3, we successfully identified four (6.5%) patients with isolated tumour cells, but none through the multilevel sectioning method. Nodal micrometastases detected by both multilevel sectioning and immunohistochemistry methods were not associated with larger tumour size, higher depth of invasion, poorer tumour grade, disease recurrence or distant metastasis. We conclude that there is no difference between the two methods in detecting nodal micrometastases. Therefore it is opined that multilevel sectioning is a feasible and yet inexpensive method that may be incorporated into routine practice to detect nodal micrometastases in centres with limited resources.
    Matched MeSH terms: Immunohistochemistry/methods*
  14. Chan SW, Kallarakkal TG, Abraham MT
    Asian Pac J Cancer Prev, 2014;15(5):2145-52.
    PMID: 24716948
    BACKGROUND: The survival rate for oral squamous cell carcinoma (OSCC) has remained generally unchanged in the past three decades, underlining the need for more biomarkers to be developed to aid prognostication and effective management. The prognostic potential of E-cadherin expression in OSCCs has been variable in previous studies while galectin-9 expression has been correlated with improved prognosis in other cancers. The aim of the present study was to investigate the expression of galectin-9 and E-cadherin in OSCC and their potential as prognostic biomarkers.

    MATERIALS AND METHODS: E-cadherin and Galectin-9 expression was examined by immunohistochemistry in 32 cases of OSCC of the buccal mucosa (13 with and 19 without lymph node metastasis), as well as 6 samples of reactive lesions and 5 of normal buccal mucosa.

    RESULTS: The expression of E-cadherin in OSCC was significantly lower than the control tissues but galectin-9 expression was conversely higher. Median E-cadherin HSCOREs between OSCCs positive and negative for nodal metastasis were not significantly different. Mean HSCOREs for galectin-9 in OSCC without lymph node metastasis (127.7 ± 81.8) was higher than OSCC with lymph node metastasis (97.9 ± 62.9) but this difference was not statistically significant.

    CONCLUSIONS: E-cadherin expression is reduced whilst galectin-9 expression is increased in OSCC. However, the present results suggest that E-cadherin and galectin-9 expression may not be useful as prognostic markers for OSCC.

    Matched MeSH terms: Immunohistochemistry/methods
  15. 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
  16. 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
  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. 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
  19. Mittal P, Klingler-Hoffmann M, Arentz G, Winderbaum L, Kaur G, Anderson L, et al.
    Biochim Biophys Acta Proteins Proteom, 2017 Jul;1865(7):846-857.
    PMID: 27784647 DOI: 10.1016/j.bbapap.2016.10.010
    The prediction of lymph node metastasis using clinic-pathological data and molecular information from endometrial cancers lacks accuracy and is therefore currently not routinely used in patient management. Consequently, although only a small percentage of patients with endometrial cancers suffer from metastasis, the majority undergo radical surgery including removal of pelvic lymph nodes. Upon analysis of publically available data and published research, we compiled a list of 60 proteins having the potential to display differential abundance between primary endometrial cancers with versus those without lymph node metastasis. Using data dependent acquisition LC-ESI-MS/MS we were able to detect 23 of these proteins in endometrial cancers, and using data independent LC-ESI-MS/MS the differential abundance of five of those proteins was observed. The localization of the differentially expressed proteins, was visualized using peptide MALDI MSI in whole tissue sections as well as tissue microarrays of 43 patients. The proteins identified were further validated by immunohistochemistry. Our data indicate that annexin A2 protein level is upregulated, whereas annexin A1 and α actinin 4 expression are downregulated in tumours with lymph node metastasis compared to those without lymphatic spread. Moreover, our analysis confirmed the potential of these markers, to be included in a statistical model for prediction of lymph node metastasis. The predictive model using highly ranked m/z values identified by MALDI MSI showed significantly higher predictive accuracy than the model using immunohistochemistry data. In summary, using publicly available data and complementary proteomics approaches, we were able to improve the prediction model for lymph node metastasis in EC.
    Matched MeSH terms: Immunohistochemistry/methods
  20. 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
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