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A mouse IgM monoclonal antibody recognizes breast and colon cancer

Bakar AF, Alitheen NB, Keong YS, Hamid M, Ali SA, Ali AM

Hybridoma (Larchmt), 2009 Jun;28(3):199-203.
PMID: 19519247 DOI: 10.1089/hyb.2007.0531

Hybridoma clone C3A8, which is a fusion product between splenic lymphocytes of Balb/c mice immunized with MCF7 breast carcinoma cells and SP2/0 myelomas, was produced and characterized. A stable clone that secreted IgM monoclonal antibody (MAb) with kappa light chain was obtained through limiting dilutions. Cell-ELISA screening, flow cytometry analysis, and immunofluorescence staining revealed that the MAb C3A8 had bound specifically and strongly to MCF7 and HT29 but cross reacted weakly or not on HeLa cell line. The MAb C3A8 reacted positively with paraffin-embedded tissues of human breast and colon cancers but there were no positive reactions on normal tissues. Western blot analysis showed the MAb recognized a 55 kDa protein, which was present in the extract of MCF7 and HT29 cell lines. Our results demonstrated that MAb C3A8 could be used for basic and clinical research of breast and colon cancers.

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Fulltext DNA mismatch repair and CD133-marked cancer stem cells in colorectal carcinoma

Cheah PL, Li J, Looi LM, Teoh KH, Ong DB, Arends MJ

PeerJ, 2018;6:e5530.
PMID: 30221090 DOI: 10.7717/peerj.5530

Background: Except for a few studies with contradictory observations, information is lacking on the possibility of association between DNA mismatch repair (MMR) status and the presence of cancer stem cells in colorectal carcinoma (CRC), two important aspects in colorectal carcinogenesis.
Methods: Eighty (40 right-sided and 40 left-sided) formalin-fixed, paraffin-embedded primary CRC were immunohistochemically studied for CD133, a putative CRC stem cell marker, and MMR proteins MLH1, MSH2, MSH6 and PMS2. CD133 expression was semi-quantitated for proportion of tumor immunopositivity on a scale of 0-5 and staining intensity on a scale of 0-3 with a final score (units) being the product of proportion and intensity of tumor staining. The tumor was considered immunopositive only when the tumor demonstrated moderate to strong intensity of CD133 staining (a decision made after analysis of CD133 expression in normal colon). Deficient MMR (dMMR) was interpreted as unequivocal loss of tumor nuclear staining for any MMR protein despite immunoreactivity in the internal positive controls.
Results: CD133 was expressed in 36 (90.0%) left-sided and 28 (70.0%) right-sided tumors (p 0.05).
Conclusion: Proficient MMR correlated with high levels of CD133-marked putative cancer stem cells in both right- and left-sided tumors, whereas significantly lower levels of CD133-marked putative cancer stem cells were associated with deficient MMR status in colorectal carcinomas found on the right.

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Fulltext Structural Studies of Epithelial Mesenchymal Transition Breast Tissues

Mohd Sobri SN, Abdul Sani SF, Sabtu SN, Looi LM, Chiew SF, Pathmanathan D, et al.

Sci Rep, 2020 02 06;10(1):1997.
PMID: 32029810 DOI: 10.1038/s41598-020-58932-5

At the supramolecular level, the proliferation of invasive ductal carcinoma through breast tissue is beyond the range of standard histopathology identification. Using synchrotron small angle x-ray scattering (SAXS) techniques, determining nanometer scale structural changes in breast tissue has been demonstrated to allow discrimination between different tissue types. From a total of 22 patients undergoing symptomatic investigations, different category breast tissue samples were obtained in use of surgically removed tissue, including non-lesional, benign and malignant tumour. Structural components of the tissues were examined at momentum transfer values between q = 0.2 nm-1 and 1.5 nm-1. From the SAXS patterns, axial d-spacing and diffuse scattering intensity were observed to provide the greatest discrimination between the various tissue types, specifically in regard to the epithelial mesenchymal transition (EMT) structural component in malignant tissue. In non-lesional tissue the axial period of collagen is within the range 63.6-63.7 nm (formalin fixed paraffin embedded (FFPE) dewaxed) and 63.4 (formalin fixed), being 0.9 nm smaller than in EMT cancer-invaded regions. The overall intensity of scattering from cancerous regions is a degree of magnitude greater in cancer-invaded regions. Present work has found that the d-spacing of the EMT positive breast cancer tissue (FFPE (dewaxed)) is within the range 64.5-64.7 nm corresponding to the 9th and 10th order peaks. Of particular note in regard to formalin fixation of samples is that no alteration is observed to occur in the relative differences in collagen d-spacing between non-lesional and malignant tissues. This is a matter of great importance given that preserved-sample and also retrospective study of samples is greatly facilitated by formalin fixation. Present results indicate that as aids in tissue diagnosis SAXS is capable of distinguishing areas of invasion by disease as well as delivering further information at the supramolecular level.

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Expression of IGFBP-rP1 in ovarian and breast cancers in association with diabetes mellitus status

Mohd Nafi SN, Siti Azrin AH, Mat Zin AA, Othman NH, Che Jalil NA

Malays J Pathol, 2019 Apr;41(1):33-39.
PMID: 31025635

INTRODUCTION: Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) is an important component of the IGF system that regulates insulin resistance-related to tumour development. The aim of this study is to investigate the expression of IGFBP-rP1 among female cancer patients who are known or not known to have Type 2 Diabetes Mellitus (T2DM).
MATERIALS AND METHODS: Using a cross-sectional design, cases of ovarian and breast cancer with clinical status of T2DM were selected over a 10-year period in Hospital Universiti Sains Malaysia. Immunohistochemical staining for IGFBP-rP1 was performed on paraffin-embedded tissues and the results were correlated with the patient's demographic and clinicopathological data.
RESULTS: A total of 152 breast cancer patients were recruited into the current study with 33.5% (51/152) patients were positive T2DM. Most of the breast cancer patients with T2DM were IGFBP-rP1-negative (66.7%, 34/51). The IGFBP-rP1 expression was significantly difference between breast cancer subjects with and without T2DM (p<0.001). There was no significant association of IGFBP-rP1 expression with data on the demographic and clinicopathological profiles of patients with breast cancer. Meanwhile, positive IGFBP-rP1 expression was evident in 44 out of 108 (40.74%) ovarian cancer cases. Among these cases, 36 were T2DM. In contrast to breast cancer cases, IGFBP-rP1 was mostly expressed among ovarian cancer patients with T2DM (66.7%, 24/36, p < 0.001). However, the -positive expression was not significantly associated with any sociodemographic and clinicopathological features of ovarian cancers.
CONCLUSIONS: Majority of breast cancer patients with T2DM did not express IGFBP-rP1. In contrast, majority of the ovarian cancer patients with T2DM expressed IGFBP-rP1.

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Fulltext Assessment of Telomere Length in Archived Formalin-Fixed, Paraffinized Human Tissue Is Confounded by Chronological Age and Storage Duration

Kong PL, Looi LM, Lau TP, Cheah PL

PLoS One, 2016;11(9):e0161720.
PMID: 27598341 DOI: 10.1371/journal.pone.0161720

Telomeres shorten with physiological aging but undergo substantial restoration during cancer immortalization. Increasingly, cancer studies utilize the archive of formalin-fixed, paraffin-embedded (FFPE) tissues in diagnostic pathology departments. Conceptually, such studies would be confounded by physiological telomere attrition and loss of DNA integrity from prolonged tissue storage. Our study aimed to investigate these two confounding factors. 145 FFPE tissues of surgically-resected, non-diseased appendixes were retrieved from our pathology archive, from years 2008 to 2014. Cases from 2013 to 2014 were categorized by patient chronological age (0-20 years, 21-40 years, 41-60 years, > 60 years). Telomere lengths of age categories were depicted by telomere/chromosome 2 centromere intensity ratio (TCR) revealed by quantitative fluorescence in situ hybridization. Material from individuals aged 0-20 years from years 2013/2014, 2011/2012, 2009/2010, and 2008 were compared for storage effect. Telomere integrity was assessed by telomere fluorescence intensity (TFI). Epithelial TCRs (mean ± SD) for the respective age groups were 4.84 ± 2.08, 3.64 ± 1.21, 2.03 ± 0.37, and 1.93 ± 0.45, whereas corresponding stromal TCRs were 5.16 ± 2.55, 3.84 ± 1.36, 2.49 ± 1.20, and 2.93 ± 1.24. A trend of inverse correlation with age in both epithelial and stromal tissues is supported by r = -0.69, p < 0.001 and r = -0.42, p < 0.001 respectively. Epithelial TFIs (mean ± SD) of years 2013/2014, 2011/2012, 2009/2010 and 2008 were 852.60 ± 432.46, 353.04 ± 127.12, 209.24 ± 55.57 and 429.22 ± 188.75 respectively. Generally, TFIs reduced with storage duration (r = -0.42, p < 0.001). Our findings agree that age-related telomere attrition occurs in normal somatic tissues, and suggest that an age-based reference can be established for telomere studies on FFPE tissues. We also showed that FFPE tissues archived beyond 2 years are suboptimal for telomere analysis.

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Fulltext Detection of epidermal growth factor receptor mutations in formalin fixed paraffin embedded biopsies in Malaysian non-small cell lung cancer patients

Shi Yeen TN, Pathmanathan R, Shiran MS, Ahmad Zaid FA, Cheah YK

J Biomed Sci, 2013 Apr 16;20:22.
PMID: 23590575 DOI: 10.1186/1423-0127-20-22

BACKGROUND: Somatic mutations of the epidermal growth factor receptor (EGFR) are reportedly associated with various responses in non-small cell lung cancer (NSCLC) patients receiving the anti-EGFR agents. Detection of the mutation therefore plays an important role in therapeutic decision making. The aim of this study was to detect EGFR mutations in formalin fixed paraffin embedded (FFPE) samples using both Scorpion ARMS and high resolution melt (HRM) assay, and to compare the sensitivity of these methods.
RESULTS: All of the mutations were found in adenocarcinoma, except one that was in squamous cell carcinoma. The mutation rate was 45.7% (221/484). Complex mutations were also observed, wherein 8 tumours carried 2 mutations and 1 tumour carried 3 mutations.
CONCLUSIONS: Both methods detected EGFR mutations in FFPE samples. HRM assays gave more EGFR positive results compared to Scorpion ARMS.

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ERG oncoprotein expression in prostate carcinoma patients of different ethnicities

Kelly GM, Kong YH, Dobi A, Srivastava S, Sesterhenn IA, Pathmanathan R, et al.

Molecular and clinical oncology, 2015 Jan;3(1):23-30.
PMID: 25469265

Overexpression of the erythroblast transformation-specific-related gene (ERG) oncoprotein due to transmembrane protease, serine 2 (TMPRSS2)-ERG fusion, the most prevalent genomic alteration in prostate cancer (CaP), is more frequently observed among Caucasian patients compared to patients of African or Asian descent. To the best of our knowledge, this is the first study to investigate the prevalence of ERG alterations in a multiethnic cohort of CaP patients. A total of 191 formalin-fixed paraffin-embedded sections of transrectal ultrasound-guided prostate biopsy specimens, collected from 120 patients treated at the Sime Darby Medical Centre, Subang Jaya, Malaysia, were analyzed for ERG protein expression by immunohistochemistry using the anti-ERG monoclonal antibody 9FY as a surrogate for the detection of ERG fusion events. The overall frequency of ERG protein expression in the population evaluated in this study was 39.2%. Although seemingly similar to rates reported in other Asian communities, the expression of ERG was distinct amongst different ethnic groups (P=0.004). Malaysian Indian (MI) patients exhibited exceedingly high expression of ERG in their tumors, almost doubling that of Malaysian Chinese (MC) patients, whereas ERG expression was very low amongst Malay patients (12.5%). When collectively analyzing data, we observed a significant correlation between younger patients and higher ERG expression (P=0.04). The prevalence of ERG expression was significantly different amongst CaP patients of different ethnicities. The higher number of ERG-expressing tumors among MI patients suggested that the TMPRSS2-ERG fusion may be particularly important in the pathogenesis of CaP amongst this group of patients. Furthermore, the more frequent expression of ERG among the younger patients analyzed suggested an involvement of ERG in the early onset of CaP. The results of this study underline the value of using ERG status to better understand the differences in the etiology of CaP initiation and progression between ethnic groups.

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Transcriptional profiling of oral squamous cell carcinoma using formalin-fixed paraffin-embedded samples

Saleh A, Zain RB, Hussaini H, Ng F, Tanavde V, Hamid S, et al.

Oral Oncol, 2010 May;46(5):379-86.
PMID: 20371203 DOI: 10.1016/j.oraloncology.2010.02.022

Despite the advances in cancer treatment, the 5-year survival rate for oral cancer has not changed significantly for the past 40 years and still remains among the worst of all anatomic sites. Gene expression microarrays have been used successfully in the identification of genetic alterations in cancer development, however, these have hitherto been limited by the need for specimens with good quality intact RNA. Here, we demonstrated the use of formalin-fixed paraffin-embedded tissues in microarray experiments to identify genes differentially expressed between cancerous and normal oral tissues. Forty-three tissue samples were macrodissected and gene expression analyses were conducted using the Illumina DASL assay. We report RNA yield of 2.4 and 0.8 microg/mm(3) from tumour and normal tissues, respectively and this correlated directly with the tissue volume used for RNA extraction. Using unsupervised hierarchical clustering, distinct gene expression profiles for tumour and normal samples could be generated, and differentially expressed genes could be identified. The majority of these genes were involved in regulation of apoptosis and cell cycle, metastasis and cell adhesion including BCL2A1, BIRC5, MMP1, MMP9 and ITGB4. Representative genes were further validated in independent samples suggesting that these genes may be directly associated with oral cancer development. The ability to conduct microarrays on formalin-fixed paraffin-embedded specimens represents a significant advancement that could open up avenues for finding genes that could be used as prognostication and predictive tools for cancer.

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Immunostaining of formalin-fixed, paraffin-embedded tissues for malignant lymphomas

Lim YC, Phang KS, Cheong SK

Malays J Pathol, 1992 Dec;14(2):85-9.
PMID: 1304629

With the advent of new monoclonal antibodies that are applicable to formalin-fixed, paraffin embedded sections, immunophenotyping is becoming increasingly important in the diagnosis and classification of lymphomas. However, multiple factors such as fixation, trypsinization and even type of antibodies used have certain effects on the final outcome of the staining procedure. In this paper we report our experience and the problems encountered in our laboratory when we first tried to establish a workable immunostaining protocol for formalin-fixed, paraffin embedded tissue sections using the immunoalkaline phosphatase technique.

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FISH analysis using PPAR γ-specific probes for detection of PAX8-PPAR γ translocation in follicular thyroid neoplasms

Sharifah NA, Zakaria Z, Chia WK

Methods Mol Biol, 2013;952:187-96.
PMID: 23100233 DOI: 10.1007/978-1-62703-155-4_13

Fluorescence in situ hybridization (FISH) is increasingly gaining importance in clinical diagnostics settings. Due to the ability of the technique to detect chromosomal abnormalities in samples with low cellularity or containing a mixed population of cells even at a single-cell level, it has become more popular in cancer research and diagnosis. Here, we describe the FISH technique for detection of PAX8-PPARγ translocation in follicular thyroid neoplasms, and the optimal protocol for the detection of this fusion gene using in archival formalin-fixed paraffin-embedded (FFPE) thyroid tissue sections.

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Fulltext Programmed cell death-ligand, thymidylate synthase and deleted in colorectal carcinoma biomarkers in colorectal carcinoma

Fauzah Abd Ghani, Reena Rehavu Zin, Maha Abdullah, Norhafizah Mohtarrudin, Ebenyi Emeka Onwe

Malaysian Journal of Medicine and Health Sciences, 2019;15(108):16-16.
MyJurnal

Introduction: It is well known that cancer cells evade the immune system with the help of programmed cell death protein 1 (PD-L1) molecule to remain undetected, causing abnormal proliferation of T-cells. PD-L1 expression on the surface of neoplastic cells inhibits cytotoxic T-cell responses which lead to negative regulation of cytokines and proliferation of T-cells. The deleted in colorectal cancer (DCC) gene belongs to the immunoglobulin superfamily. It is a candidate of the tumour suppressor gene by regulating apoptosis. DCC assessment gives an insight into progno-sis in patients with advanced stages of CRC. Thymidylate synthase (TYMS) is a highly conserved enzyme involved in DNA synthesis. TYMS has been an important target for cancer chemotherapy because of its central, rate-limiting role in de novo synthesis of thymidylate. Expression of PD-L1, TYMS and DCC has been demonstrated to confer a prognostic value in CRC but none have been completely validated for patient care. This study aimed to determine the prognostic and predictive potential of PD-L1, TYMS, and DCC biomarkers in CRC. Methods: The expression of these biomarkers was evaluated immunohistochemically in 91 formalin-fixed paraffin-embedded (FFPE) archival tumour samples from patients that underwent surgical resection. Results: There was high expression of DCC in most cases; 84.6% (77/91). TYMS expression at a high level score was 46.2% (42/91) and at low level was 53.8% (49/91). Majority of cases had low PD-L1 expression in 93.4% (86/91) cases and high expression was detected in 6.6% (6/94) of cases. In addition, there was a significant association between TYMS expression with gender (P < 0.05) with distribution of TYMS expression detected at high level was 76.2% in male and 23.8% in female. The Kaplan-Meier survival plot showed mean overall survival in patients with PD-L1 with high expression to be 22 months, which pre-dicts better survival. TYMS low expression showed mean overall survival of 90 which also indicated better survival. DCC high expression showed mean overall survival of 90 which indicated better survival. The correlation between the biomarkers and overall survival were not statistically significant. Conclusion: The results from this study suggest that PD-L1, TYMS and DCC expression could be used as biomarkers to predict treatment outcome in CRC. PD-L1 overexpression predicts patients who could benefit from anti-PD-1 and anti-PD-L1 immunotherapy whilst TYMS low expression predicts patients who could benefit from 5-fluorouracil therapy. DCC high expression tumours predicts a better prognosis and overall survival compared to DCC-negative tumours in advanced CRC.

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Classifying DLBCL according cell of origin using Hans algorithm and its association with clinicopathological parameters: A single centre experience

Wn Najmiyah WAW, Azlan H, Faezahtul AH

Med J Malaysia, 2020 03;75(2):98-102.
PMID: 32281588

INTRODUCTION: In recent years, "double hit" and "double protein" involving gene rearrangement and protein expression of c-MYC and BCL2 and/or BCL6 are the most used terms to describe poor prognostic factors in diffuse large B-cell lymphoma (DLBCL). This study was to determine the frequency of double or triple protein expression by using immunohistochemistry (IHC) and comparing the result with clinicopathological features and cell of origin (COO) classification.
METHODS: We conducted a cross-sectional study by using 29 archived formalin-fixed paraffin embedded tissue blocks of DLBCL. All the samples were evaluated for the subgrouping of COO DLBCL was determined by expression of CD10, BCL6 and MUM1 based on Hans classification. In addition, expressions of c-MYC, BCL2 and BCL6 were detected by IHC.
RESULTS: Among the 29 cases, MYC, BCL2 and BCL6 proteins were detected in 72.4%, 62.1% and 62.1% of patients, respectively. Concurrent expression (c-MYC positive/BCL2 positive and/or BCL6 positive) was present in 58.6% of patients. 34.5% were categorised as germinal centre like (GCB) subgroup and 65.5% were categorised as nongerminal centre like (non-GCB) subgroup. Among the clinicopathological features, the double/triple protein expression lymphoma was significantly associated with elevated LDH level (p=0.018), IPI score (p=0.003), Ann Arbor stage (p=0.011) and complete response rate (p=0.011).
CONCLUSION: Double/triple protein lymphoma was strongly associated more adverse clinical risk factors. Thus, analyses of MYC, BCL2 and BCL6 expression by IHC represents a rapid and inexpensive approach to risk-stratify patients with DLBCL at diagnosis.

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Fulltext MGMT and SPOCK2 Promoter Methylation in diffuse large B-Cell Lymphoma: a study in two tertiary health centres in the East Coast of Malaysia

Norafiza Zainuddin, Lailatul Jalilah Mohd Ridah, Aqilah Nabihah Omar, Norlelawati A. Talib, Naznin Muhammad, Faezahtul Arbaeyah Hussain

Jurnal Sains Kesihatan Malaysia, 2017;15(2):77-82.
MyJurnal

MGMT (O6
-Methylguanine-DNA Methyltransferase) suppresses tumor development by removing alkyl adduct, while
SPOCK2 (SPARC/Osteonectin CWCV and Kazal-like domains proteoglycan) abolishes the inhibition of membrane-type
matrix metalloproteinases (MT-MMP) which leads to angiogenesis. Hence, MGMT methylation may initiate malignant cells
transformation. In contrast, SPOCK2 methylation is hypothesized not to be a common event in diffuse large B-cell lymphoma
(DLBCL). In this study, we examined the methylation status of MGMT and SPOCK2 in DLBCL as in Malaysia the information
is extremely lacking. A total of 88 formalin-fixed paraffin-embedded tissue of patients diagnosed with DLBCL from the
year 2006 to 2013 were retrieved from Hospital Universiti Sains Malaysia, Kelantan and Hospital Tengku Ampuan Afzan,
Pahang. Methylation-specific polymerase chain reaction (MSP) was used to examine the methylation status of both genes.
Interestingly, methylation of MGMT was detected in all the 88 DLBCL samples, whereas SPOCK2 was found to be methylated
in 83 of 88 (94.3%) DLBCL cases. Our study showed a remarkably high percentage of promoter methylation of both
MGMT and SPOCK2 genes. Our finding also negates initial expectation that SPOCK2 methylation would be an uncommon
event in the majority of DLBCL cases. This study has shown a very high percentage of promoter methylation of MGMT and
SPOCK2 in the DLBCL cases studied by MSP, using archival lymphoma tissues. Nonetheless, additional research is needed
to quantitatively evaluate MGMT and SPOCK2 methylation, and to analyse gene expression and/or protein expression in
order to further understand the role of MGMT and SPOCK2 methylation in the pathogenesis of DLBCL.

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p53 codon 72 polymorphisms and random amplified polymorphic DNA analysis of non-melanoma skin cancer through archival formalin-fixed paraffin-embedded tissue

Yoke-Kqueen C, Ab Mutalib NS, Sidik SM, Learn-Han L, Geok-Chin T

Oncol Rep, 2012 Mar;27(3):753-63.
PMID: 22159872 DOI: 10.3892/or.2011.1581

Non-melanoma skin cancer (NMSC) is classified among the ten most frequent cancers in Malaysia. A common polymorphism at codon 72 of the p53 tumor suppressor gene and its influence on cancer risk has been studied for different types of cancer with mixed and inconsistent results with limited published data on the Malaysian population so far. In the present study, the frequency of p53 codon 72 polymorphism in 60 patients with NMSC was investigated from archival formalin-fixed paraffin-embedded (FFPE) tissue obtained from Hospital Universiti Kebangsaan Malaysia (HUKM). Additionally, random amplified polymorhic DNA -polymorphic chain reaction (RAPD-PCR) was employed for preliminary biomarker development. NMSC FFPE samples (70%) possess Arg/Arg, 20% with Pro/Pro and 10% with Arg/Pro. In total, there was no significant difference in the p53 codon 72 genotypes between histological types of NMSC, gender, race, tumor location and age group. However, there was an apparent age-associated increase in the Arg/Arg genotype but did not reach statistical significance (P=0.235). NMSC types and demographic characteristics did not influence genotype distribution. On the other hand, BCC and SCC distributions are influenced by age group, race and tumor location.

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Fulltext Decreased Expression of Inhibitor of Caspase-Activated DNase (ICAD) in Renal Cell Carcinoma - Tissue Microarray of Human Samples

Rajandram R, Razack AH, Ng KL, Gobe GC

J Kidney Cancer VHL, 2016;3(1):1-11.
PMID: 28326275 DOI: 10.15586/jkcvhl.2016.47

Although primary localised tumours of renal cell carcinoma (RCC) can be treated relatively successfully with surgery, metastatic RCC has poor prognosis because of late diagnosis and resistance to therapies. In the present study, we were interested in profiling the protein expression of "inhibitor of caspase-activated DNase" (ICAD), an apoptosis inhibitor, in kidney cancer and its paired normal kidney. Immunohistochemistry with automated batch staining and morphometry using digital pathology were used to compare ICAD in 121 RCC specimens with their paired normal kidney tissue. Tissue microarray of formalin-fixed, paraffin-embedded archival tissue was used. Intensity and localisation of ICAD were compared between normal and cancer samples, and against grading within the cancers. The results demonstrated that, in this cohort, ICAD was highly expressed in the proximal tubular epithelium of normal kidney, and significantly decreased in clear cell RCC tissue (p < 0.05) as well as other subtypes of RCC (p < 0.01) compared with normal kidney. There was a tendency towards nuclear localisation of ICAD in clear cell RCC, but not in other subtypes of RCC. No significant association was found between ICAD intensity and grade of RCC. In summary, down-regulation of ICAD occurs in RCC. ICAD normally inhibits DNA fragmentation and apoptosis; thus, its down-regulation was unexpected in a cancer known for its resistance to apoptosis. However, these RCC samples were from primary, not metastatic, RCC sites, and down-regulated ICAD may be part of a progressive pathway that promotes RCC metastasis.

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Fulltext The Role of ISL1 and LHX5 LIM Homeobox Genes in Bladder Tumourigenesis

Akhir MKAM, Choy CS, Abdullah MA, Ghani FA, Veerakumarasivam A, Hussin H

Malays J Med Sci, 2020 Feb;27(1):37-45.
PMID: 32158343 MyJurnal DOI: 10.21315/mjms2020.27.1.4

Introduction: Lin-11, Isl-1 and Mec-3 domains (LIM) homeobox genes are among the most important sub-families of homeobox genes. These genes are thought to play an important role in cancer. In this study, the protein expression of these genes was examined in urothelial carcinoma of the bladder. The expression pattern of Islet-1 (ISL1) and LIM homeobox 5 (LHX5) across different cancer stages and grades, as well as the association between the protein expression of these genes and patient demographics and clinicopathological features, were examined.
Methods: A total of 100 formalin-fixed paraffin-embedded urothelial carcinoma tissues were selected from the Department of Pathology, Hospital Kuala Lumpur and the protein expression of ISL1 and LHX5 was determined using immunohistochemistry.
Results: Positive expression of ISL1 and LHX5 was detected in 94% and 98% of the samples, respectively. There were no distinct LHX5 expression patterns associated with different cancer stages, but the proportion of high-expressing tumours was higher in high-grade tumours. In addition, there was a significant association between the expression of LHX5 and tumour grade. The proportion of tumours expressing high levels of ISL1 was found to be highest in later stage tumours.
Conclusion: The high percentage of tumours expressing both these genes suggests that ISL1 and LHX5 play an important role in bladder tumourigenesis across multiple stages.

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Fulltext Microvessel density and vascular endothelial growth factor receptors in breast carcinoma under the influence of rapamycin and platelet factor 4

Muhammad Sakri MS, Abdul Rahman WFW, Tengku Din TADA, Idris FM, Jaafar H

Indian J Pathol Microbiol, 2020 4 23;63(2):205-209.
PMID: 32317516 DOI: 10.4103/IJPM.IJPM_496_19

Background: Vascular endothelial growth factor receptors (VEGFRs) are major endothelial growth factor receptors that influence the growth of a tumor. Microvessel density.
(: MVD) is the quantification method of various aspects of tumor vasculature that indicates angiogenic activity. This study aims to analyze the correlation between MVD to the expression of VEGFRs on breast cancer tissue.
Materials and Method: A total of 60 N-methyl-N-nitrosourea (MNU)-induced breast carcinomas in rats were suppressed by using antiangiogenic drugs. The rats were then sacrificed, and the tumor was fixed in 10% formalin, paraffin embedded, and immunohistochemistry stained using VEGFRs and CD34.
Result: One-way ANOVA test showed a significant difference in all markers that have been used (P < 0.05) on MNU-breast tumor treated with rapamycin (M= 90.1664, SD= 7.4487), PF4 (M= 93.7946, SD= 7.1303) and rapamycin + PF4 (M= 93.6990, SD= 1.8432). We obtained a significant reduction of MVD count on breast carcinoma for rapamycin group (M= 25.6786, SD= 9.7075) and rapamycin + PF4 group (M= 30.5250, SD= 13.6928) while PF4 group (M=47.7985, SD=4.8892) showed slightly increase compared to control (M= 45.1875, SD= 4.4786). There was a moderately strong, positive correlation between angiogenic markers; Flt-1 (r= 0.544, n=60, P < 0.005) and Flt-4 (r= 0.555, n= 60, P < 0.005) while Flk-1 (r= 0.797, n= 60, P < 0.005) showed a strong, positive correlation with MVD.
Conclusion: MVD was strongly correlated to the VEGFRs expression on breast carcinoma.

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Fulltext Intra-operative frozen section consultation: concepts, applications and limitations

Jaafar H

Malays J Med Sci, 2006 Jan;13(1):4-12.
PMID: 22589584

Intra-operative frozen section plays an important role in the management of surgical patients and yet it must be used prudently to avoid the indiscriminate usage of this important technique. As it is subjected to many limitations in comparison to the paraffin embedded tissue sections, this review aims to highlight the important concepts and principle of intra-operative frozen section consultation as well as discussing the limitations of this technique. This will then allow the endusers of this technique to be more informed and more selective in their decisions when requesting for a frozen section report.

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Fulltext Neuronal Cell Death and Mouse (Mus musculus) Behaviour Induced by Bee Venom

Oktiansyah R, Juliandi B, Widayati KA, Juniantito V

Trop Life Sci Res, 2018 Jul;29(2):1-11.
PMID: 30112137 DOI: 10.21315/tlsr2018.29.2.1

Neuronal cell death can occur in a tissue or organ, including the brain, which affects memory. The objectives of this study were to determine the dose of bee venom that causes neuronal death and analyse the alteration of mouse behaviour, focusing in particular on spatial memory. Fifteen male mice of Deutsche Denken Yoken (DDY) strain were divided into control and treatment groups. Bee venom was injected six times for two weeks intraperitoneally with 1.88 mg/kg, 3.76 mg/kg, 5.6 mg/kg, and 7.48 mg/kg doses of venom. Brain histology was studied using haematoxylin-eosin stained paraffin embedded 5 μm coronal sections. A Y maze test was used to assay behaviour. Parameters observed were the number of dead neurons and the percentage of mice with altered behaviour. ANOVA showed that the effects of bee venom were significantly different in the case of the neuronal death parameter but were not significantly different in the case of the mice behaviour parameter. Duncan's Multiple Range Test (DMRT) demonstrated that P4 (7.48 mg/kg) gave the highest effect of bee venom to promote neuronal death.

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Fulltext The resin-embedded cornea prepared via rapid processing protocol : a good histomorphometric target for clinical investigation in ophthalmology and optometry

Cheah PS, Mohidin N, Mohd Ali B, Maung M, Latif AA

Malays J Med Sci, 2008 Jul;15(3):49-54.
PMID: 22570589

This study illustrates and quantifies the changes on corneal tissue between the paraffin-embedded and resin-embedded blocks and thus, selects a better target in investigational ophthalmology and optometry via light microscopy. Corneas of two cynomolgus monkeys (Macaca fascicularis) were used in this study. The formalin-fixed cornea was prepared in paraffin block via the conventional tissue processing protocol (4-day protocol) and stained with haematoxylin and eosin. The glutaraldehyde-fixed cornea was prepared in resin block via the rapid and modified tissue processing procedure (1.2-day protocol) and stained with toluidine blue. The paraffin-embedded sample exhibits various undesired tissue damage and artifact such as thinner epithelium (due to the substantial volumic extraction from the tissue), thicker stroma layer (due to the separation of lamellae and the presence of voids) and the distorted endothelium. In contrast, the resin-embedded corneal tissue has demonstrated satisfactory corneal ultrastructural preservation. The rapid and modified tissue processing method for preparing the resin-embedded is particularly beneficial to accelerate the microscopic evaluation in ophthalmology and optometry.

Matched MeSH terms: Paraffin Embedding

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