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Low cost immunohistochemistry bench for developing countries

Ch'ng ES, Khiro FI

Malays J Pathol, 2018 Aug;40(2):209-211.
PMID: 30173241

No abstract available.

Matched MeSH terms: Immunohistochemistry/economics*; Immunohistochemistry/methods*
Fulltext The use of immunohistochemistry in an oral pathology laboratory

Ajura AJ, Sumairi I, Lau SH

Malays J Pathol, 2007 Dec;29(2):101-5.
PMID: 19108402 MyJurnal

Immunohistochemistry has become part of normal routine diagnostic work in the Stomatology Unit, Institute for Medical Research, Kuala Lumpur. Of 9523 cases received from the year 2000 to 2005, 197 cases (2.1%) required immunohistochemical staining. These cases ranged from benign to malignant lesions. They include lymphomas (n=41), epithelial tumours (n=29), neural lesions (n=21), fibroblastic/myofibroblastic tumours (n=16), small round cell tumour (n=11), vascular tumours (n=4), smooth muscle tumours (n=4), myxomatous tumours (n=4) and skeletal muscle tumours (n=1). In most of the cases (69.5%), immunohistochemical staining was mandatory to reach a definite diagnosis, while 60 cases (30.5%) required immunohistochemistry in confirming the diagnosis. In 32 cases (16.2%), definitive diagnosis could not be made due to the small size of the specimens received or the results of immunohistochemistry were inconclusive. Standardization of techniques, competent medical laboratory technologists and sufficient budget allocation are important in producing a high quality immunohistochemistry service.

Matched MeSH terms: Immunohistochemistry/economics; Immunohistochemistry/standards; Immunohistochemistry/utilization*
Rapid 'technological lock in' and pathology - Is technology moving too fast?

Moorchung N

Malays J Pathol, 2019 Apr;41(1):1-5.
PMID: 31025631

The term "Lock In" as applied to Science and Technology refers to a technology which has been utilised for a certain amount of time and it has been determined that the technology is viable and cost effective. An analysis of the technological advancements in pathology over a period of time shows that the newer technologies in contrast to the older technologies are reaching a state of "Technological Lock In" much faster. Three different discoveries, the development of the autopsy as a research tool, the discovery of the microscope and immunohistochemistry illustrate how rapidly "Technological Lock In" is being achieved with the passage of time. Three probable scenarios are possible because of this rapid "Technological Lock In". Technology may continue to progress at the same pace (an ideal scenario), may plateau until pathologists accept and absorb new technologies or thirdly, develop very rapidly so that the technology may never reach pathology practice. What will the future be? How will technology influence the principles and practices of Pathology? Only time will tell.

Matched MeSH terms: Immunohistochemistry
Fulltext Hodgkin lymphoma mimicking a large soft tissue sarcoma of the shoulder: the essential role of immunohistochemistry in histopathological diagnosis

Zainal Abidin I, Zulkarnaen AN, Dk Norlida AO, Wai Hoong C, Huong Ling L

Malays J Med Sci, 2012 Oct;19(4):72-6.
PMID: 23613651 MyJurnal

The shoulder and axillary regions contain various complex anatomical structures in close proximity, many of which can give rise to neoplasms. Determining the origin and hence the exact diagnosis of advanced (diffuse) tumours in this region may become problematic. In view of the tumour morphology and the affected location in this case, we highlighted the importance of Hodgkin lymphoma immunohistochemistry interpretation in a tumour which was initially suspected to be a soft tissue sarcoma.

Matched MeSH terms: Immunohistochemistry
Fulltext Nuclear IHC enumeration: A digital phantom to evaluate the performance of automated algorithms in digital pathology

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*
Fulltext Post-operative immunohistochemical diagnosis of two synchronous primary non-small cell lung cancers in a single lobe

Sachithanandan A, Nor Y

Med J Malaysia, 2013 Apr;68(2):175-6.
PMID: 23629571 MyJurnal

Synchronous primary non-small cell lung cancers (NSCLC) are rare and may be discovered unexpectedly following lung resection. Discrimination from intrapulmonary metastases is important to guide treatment and prognosis but is difficult solely on clinical or radiological findings. Histopathological evaluation with immunohistochemistry (IHC) markers can prove decisive and should feature in the diagnostic algorithm of such patients. We report a rare case of two synchronous primary NSCLCs diagnosed post operatively following pathological examination of the resected lobe, highlighting the value of IHC and discuss the management of such patients.

Matched MeSH terms: Immunohistochemistry
Frequent detection of human herpesvirus 6 in oral carcinoma

Yadav M, Chandrashekran A, Vasudevan DM, Ablashi DV

J Natl Cancer Inst, 1994 Dec 07;86(23):1792-4.
PMID: 7966419
Matched MeSH terms: Immunohistochemistry
Fulltext Construction and validation of a mammalian expression vector for in utero electroporation study of mir-3099 in the Mouse Neocortex

Shahidee Zainal Abidin, Han-Chung Lee, Sze-Zheng Fam, Syahril Abdullah, Norshariza Nordin, Pike-See Cheah, et al.

Malaysian Journal of Medicine and Health Sciences, 2018;14(101):20-29.
MyJurnal

Introduction: MiR-3099 was reported to play a role in neuronal cell differentiation/function in the brain during late embryonic and early neonatal development. To further explore its potential regulatory effects on embryonic brain development, this study aims to construct and validate an expression vector of miR-3099 for future gain-of-function and loss-of-function studies. Methods: pCAG-eGFP vector was modified to include IRES2 and miR-3099 with 150bp upstream and downstream genomic sequences. The newly constructed vector, pCAG-miR-3099-IRES2-eGFP, consists of CAG promoter. The in vitro expression level of miR-3099 was measured using stem-loop RT-qPCR after it was transfected into 293FT cell. Later, the vector was electroporated into the embryonic brain at E15.5. Three days later, the E18.5 embryonic brain was harvested and cryopreserved. Immunohistochemistry was performed by using antibody against eGFP to validate the in utero expression of the transgene in the neocortex of the brain. Results: Our finding showed that, the expression level of miR-3099 was significantly upregulated (p

Matched MeSH terms: Immunohistochemistry
Fulltext Laryngeal Leiomyosarcoma: A Rare Case

Ng BHK, Tang IP, Suhashini G, Chai CK

Indian J Otolaryngol Head Neck Surg, 2019 Oct;71(Suppl 1):795-797.
PMID: 31742066 DOI: 10.1007/s12070-018-1553-7

Laryngeal leiomyosarcoma is a rare smooth muscle malignancy of the head and neck region. Diagnosis is based on immunohistochemistry. Here we present a case of laryngeal leiomyosarcoma that was diagnosed and treated in our center, focusing on the clinical features, histological diagnosis and management of this rare disease.

Matched MeSH terms: Immunohistochemistry
Aptahistochemistry in diagnostic pathology: technical scrutiny and feasibility

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*; Immunohistochemistry/trends
Fulltext A study of proliferating cell nuclear antigen expression in benign, borderline and malignant epithelial tumours of ovary

Khoo JJ

Med J Malaysia, 2002 Jun;57(2):161-8.
PMID: 24326646

Borderline epithelial tumours or low malignant potential epithelial tumours of ovary have a better prognosis and hence it is important to distinguish this group from their malignant counterparts. Several studies were done correlate the growth rates of tumours with nuclear proteins that are expressed in proliferating cells. Immunohistochemical stains with monoclonal antibodies against proliferating cell nuclear antigen (PCNA) were used on 51 archival epithelial tumours of ovary. The percentage of PCNA reactivity showed means of 1.1%, 2.3% and 27.7% with benign, borderline tumours and malignant epithelial tumours of ovary. respectively. The % PCNA reactivity was found to be significantly different amongst the three group (p<0.001). Thus , PCNA reactivity can help to differentiate borderline tumours from malignant epithelial tumours of ovary. This is critical when light microscopic appearances are equivocal and therapeutic management is dependent on the diagnosis.

Matched MeSH terms: Immunohistochemistry
Malignant teratoma of the thyroid with predominantly neuroepithelial differentiation. Fine needle aspiration cytologic, histologic and immunocytochemical features of a case

Jayaram G, Cheah PL, Yip CH

Acta Cytol., 2000 May-Jun;44(3):375-9.
PMID: 10833994

BACKGROUND: Teratoma of the thyroid in adults is extremely rare, and most are malignant. Only nine cases have been adequately documented in the English-language literature, and there are no reports detailing the fine needle aspiration (FNA) cytologic characteristics.

CASE: A 32-year-old female presented with a left-sided nodular thyroid mass with left cervical lymphadenopathy. FNA cytology of the thyroid and lymph nodes was done. The cytologic and immunocytochemical features were that of a small round cell tumor with neuroepithelial (NE) differentiation, metastasizing to the cervical nodes. Microscopic study of the thyroidectomy specimen showed a tumor showing an NE pattern with occasional islands of squamous and cuboidal epithelium, leading to a diagnosis of malignant teratoma.

CONCLUSION: Knowledge of FNA cytologic features of rare but highly malignant lesions like thyroid teratomas allow early recognition so that suitable and possibly aggressive treatment protocols can be adopted in the hope of prolonging survival.

Matched MeSH terms: Immunohistochemistry
Fulltext Fine needle aspiration cytology of metastatic renal cell carcinoma - a case report

Wan Muhaizan Wan Mustaffa, Sharifah Noor Akmal Syed Husain

Medicine & Health, 2006;1(1):75-80.
MyJurnal

Fine needle aspiration cytology under radiologic guidance for diagnosis of renal cell carcinoma is well established and is increasingly utilized. This is because renal cell carcinoma displays fairly characteristic cellular features permitting correct cytologic identification. We present a case of a 66-year-old man who had advanced renal cell carcinoma with spread to aortic and cervical lymph nodes, lungs and liver. Fine needle aspiration cytology of the para-aortic mass showed tight clusters of malignant cells with abundant and vacuolated cytoplasm consistent with renal cell carcinoma. Histology of the left cervical lymph nodes together with immunohistochemistry findings were consistent with the cytologic diagnosis of metastatic renal cell carcinoma. The patient succumb to his illness three years after the diagnosis was made.

Matched MeSH terms: Immunohistochemistry
Fulltext P53/MDM2 co-expression correlates with the tumour differentiation in oral squamous cell carcinoma - a retrospective study and a systematic review

Choon, Y.F., Ramanathan, A., Ali, H., Ghani, W.M.N., Cheong, S.C., Zain, R.B.

Ann Dent, 2011;18(1):8-17.
MyJurnal

Background: MDM2 and p53 are involved in a negative feedback loop where p53 regulates MDM2 at the transcriptional level. MDM2, in turn, downregulates p53. This co-ordinated interaction between these proteins is set to play an important role in the regulation of cell cycle progression following DNA damage to cells. The over-expression of both p53 and MDM2 has been reported in various cancers. However there are only few studies discussing the co-expression of MDM2 with p53 in oral squamous cell carcinoma Aim: The purpose of this study was to determine the correlation of co-expression of p53, MDM2, and Ki-67 proteins with clinico-pathological factors in oral squamous cell carcinoma (OSCC) and to conduct a systematic review of the co-expression of p53/MDM2.

Method: This is a retrospective descriptive study and a systematic review. Formalin-fixed paraffinembedded tissues from 45 OSCC cases were stained by immunohistochemistry (IHC) for p53, MDM2, and Ki-67 proteins.

Results: Immuno-reactivity for p53, MDM2, and Ki-67 was seen in 75.6%, 97.8%, and 62.2% cases of OSCC respectively. The co-expression of p53 and MDM2 (p53/MDM2) was detected in 97.1%, however there was no significant correlation between p53 and MDM2 expression. Notably, p53/MDM2 coexpression was significantly associated with tumour differentiation (p-value = 0.045). The Ki-67LI was not significantly associated with neither MDM2 nor p53/MDM2 co-expression (p-value = 0.268, 0.916 respectively).

Conclusion: The expression of MDM2 was not signif icantly associated with p53 expression suggesting that MDM2 expression is mediated by p53-independent pathways or mutated p53 could not induce the expression of MDM2 in this set of OSCCs. The only clinico-pathological parameter that correlates significantly with co-expression of p53/MDM2 is tumour differentiation where it is suggestive that the co-expression of these 2 proteins is indicative of aggressive tumour behavior.

Matched MeSH terms: Immunohistochemistry
Fulltext Evaluation of the Role Played by Cyclin D1 as a Diagnostic and Prognostic Marker in the Progression of Oral Carcinogenesis

John RR, Ravindran C, Malathi N, Aruna RM

J Maxillofac Oral Surg, 2018 Sep;17(3):389-395.
PMID: 30034160 DOI: 10.1007/s12663-018-1087-2

Abstract: Cyclin D1 is linked with the development and progression of oral squamous cell carcinoma (OSCC). This case-control study was directed to characterise the immunoreactivity of the protein cyclin D1 and its correlation with the clinicopathological parameters of patients with OSCC and potentially malignant disorders (PMD). A group of patients with OSCC were followed up after treatment, and the cyclin D1 expression was reviewed for correlation of cyclin D1 expression with prognosis of the patients.
Methodology: Sixty individuals were included in this study: OSCC (20), PMD (20) and Control (20). Immunohistochemistry assay was evaluated. The clinicopathological parameters were correlated with the staining intensity of cyclin D1. The results were subjected to Pearson's correlation test.
Results: Age, gender and site showed no statistically significant correlation with cyclin D1 expression in OSCC and PMD. The cyclin D1 score did not show a significant difference with histopathological diagnosis of OSCC. Cyclin D1 was not expressed in 60% of the Control and 30% PMD cases while the expression of cyclin D1 was seen in 100% of OSCC cases although cyclin D1 score did not show a statistically significant association in the prognosis of the disease among the OSCC patients.

Matched MeSH terms: Immunohistochemistry
Fulltext Malignant Transformation of a Rosette-Forming Glioneuronal Tumor with IDH1 Mutation: A Case Report and Literature Review

Jayapalan RR, Mun KS, Wong KT, Sia SF

World Neurosurg X, 2019 Apr;2:100006.
PMID: 31218281 DOI: 10.1016/j.wnsx.2018.100006

Background: Rosette-forming glioneuronal tumor (World Health Organization grade I) is considered as a benign tumor with very low potential for progression. The potential for malignant transformation of this tumor is not known and has never been reported before in literature.
Case Description: We report a 42-year-old man, diagnosed with rosette-forming glioneuronal tumor of the fourth ventricle with a positive isocitrate dehydrogenase 1 mutation, progressed to glioblastoma after 6 years from diagnosis. We discuss the clinical history, radiological findings, and histopathological characteristic with immunohistochemistry findings observed in this unique case.
Conclusions: Despite being acceptable as benign, based on our observations in this case, there is a potential for malignant transformation of rosette-forming glioneuronal tumor. The role of isocitrate dehydrogenase 1 mutation leading to malignant transformation could not be established as our finding is novel and further prospective studies are required to prove this association.

Matched MeSH terms: Immunohistochemistry
Swelling on the Upper Lip: A Diagnostic Challenge

Tegginamani AS, Hs V, Wanjari SG, Dubey G

J Coll Physicians Surg Pak, 2019 Aug;29(8):796.
PMID: 31358112 DOI: 10.29271/jcpsp.2019.08.796
Matched MeSH terms: Immunohistochemistry
Qualitative and quantitative assessment of immune cells in Oral Mucosal Lichen Planus (OMLP)

Sinon S, Rich A, Firth N, Seymour G

Sains Malaysiana, 2013;42:65-71.

Cell mediated immunity is currently thought to be involved in the pathogenesis of oral mucosal lichen planus (OMLP). However, literature reveals there is no large scale data of immunohistochemistry (IHC) study on these immune cell populations. The aim of this study was to assess and compare immune cell surface identification markers CD3, CD4, CD8, CD19 and CD83 between the OMLP (n=40) and non-specific inflammatory lesions (as control group) (n=10) qualitatively and quantitatively. Kruskal-Wallis and Mann Whitney U tests have been used to make comparison between the test and control group, p values of less than 0.05 was considered to be statistically significant. T cell surface markers (CD3+, CD4+ and CD8+), B cells (CD19+) and mature dendritic cells (CD83+) showed intense immunostaining in OMLP tissues with a significantly higher expression of positive cells than in the control group (p<0.05). CD3, CD4 and CD8+ve T cells were the predominant inflammatory cell type in OMLP rather than CD19+ B cells, supporting the role of Th1 cells in the pathogenesis of OMLP. CD83+ mature dendritic cells were present in the least number and were mostly localized to areas where there were aggregates of lymphocyte. There was a positive correlation and direct relationship between T and B lymphocyte subsets whereby as one subset increased, the other follows.

Matched MeSH terms: Immunohistochemistry
Loss of Interleukin-17RA Expression is Associated with Tumour Progression in Colorectal Carcinoma

Chai BY, Yip WK, Dusa N, Mohtarrudin N, Seow HF

Pathol Oncol Res, 2020 Oct;26(4):2291-2298.
PMID: 32462420 DOI: 10.1007/s12253-020-00820-4

Interleukin-17 (IL-17) is a pro-inflammatory cytokine found in various cancers. Current evidence indicates that IL-17 plays a vital role in tumour initiation and progression in colorectal carcinoma (CRC) via binding with its receptor, IL-17RA. However, the association between clinicopathological features and presence of IL-17 and IL-17RA protein in primary CRC tissues remains unclear. This study also investigates the difference between the presence of IL-17 and IL-17RA in the paired tumour tissues versus adjacent normal tissues. The presence of IL-17RA and IL-17 protein in primary CRC tissues was determined by immunohistochemistry. Associations between clinicopathological features and IL-17RA and IL-17 immunoreactivity, were analyzed by χ2 tests. We found that both IL-17RA (p = 0.001) and IL-17 (p = 0.025) in tumour cells of primary CRC tissues was significantly lower as compared to adjacent normal tissue. Positive immunoreactivity for IL-17RA and IL-17 were detected in 51.0% and 16.8% of tumour tissues, respectively. Furthermore, negative immunoreactivity of IL-17R was significantly associated with advanced stage according to TNM classifier (p = 0.027), high grade of tumour (p = 0.019), increased depth of tumour invasion (p = 0.023) and vascular invasion (p = 0.039). Positive IL-17 immunoreactivity was associated with advanced stage (p = 0.008) and lymph node metastasis (p = 0.008). Thus, this study suggests that the loss of IL-17RA expression occurs as tumour progresses and this may predict the aggressiveness of tumour whilst expression of IL-17 promotes tumour progression and lymph node metastasis. Thus, loss of IL-17RA could be a useful prognostic biomarker for tumour progression in CRC patients.

Matched MeSH terms: Immunohistochemistry
Fulltext Calcitriol-mediated Reversible Hypercalcemia in a Patient with Primary Adrenal Lymphoma

Mir SA, Masoodi SR, Wani AI, Ahmad SN, Hameed I

Malays J Med Sci, 2016 Nov;23(6):118-122.
PMID: 28090186 DOI: 10.21315/mjms2016.23.6.13

Primary adrenal lymphomas (PAL) are rare occurrences with only less than 150 cases reported in the literature. Two-thirds of these cases were reported in the last decade due to the advancements in imaging techniques and immunohistochemistry. The non-specific signs and symptoms have resulted in a delayed onset of symptoms and diagnosis of these tumors. Reports of the results of chemotherapy are not gratifying, and most patients die within one year of the diagnosis. We report a 65-year-old male with adrenal non-Hodgkin's lymphoma (NHL), who presented with hypercalcemia and renal failure. We reviewed all adrenal NHL cases presented with hypercalcemia and attempted to comprehend its etiology and overall survival effect.

Matched MeSH terms: Immunohistochemistry

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