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  1. Azizan N, Hayati F, Tizen NMS, Farouk WI, Masir N
    Investig Clin Urol, 2018 07;59(4):232-237.
    PMID: 29984337 DOI: 10.4111/icu.2018.59.4.232
    Purpose: To evaluate the expression of estrogen receptor (ER)-beta and Ki67 in prostate cancer and study their relationship.

    Materials and Methods: We analyzed 101 cases of prostate adenocarcinoma diagnosed from January 2011 to June 2015 in 100 patients. Immunohistochemical staining of ER-beta and Ki67 was analyzed according to Gleason score categorized into prognostic groups of 1 to 5. Double-immunofluorescent staining of ER-beta and Ki67 was performed in a total of 20 cases to study the co-expression and the relationship between these markers within the same tumor.

    Results: A total of 53 of 101 cases (52.5%) were positive for ER-beta expression. There was a positive correlation whereby a high percentage of ER-beta expression was seen in the higher prognostic groups (groups 4 and 5; p=0.007). High Ki67 expression was observed in the higher prognostic group, whereas low Ki67 or negative expression was found in the lower prognostic group (p<0.001). The majority of cases evaluated with double-immunofluorescent staining (14/20) showed co-expression of ER-beta and Ki67 at the individual cell level.

    Conclusions: ER-beta and Ki67 are independent tumor markers in high prognostic groups. Hence, co-expression of ER-beta and Ki67 indicates a more aggressive tumor with a poorer prognosis.

  2. Phang KC, Hussin NH, Abdul Rahman F, Tizen NMS, Mansoor A, Masir N
    Malays J Pathol, 2019 Aug;41(2):101-124.
    PMID: 31427546
    INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive type of non-Hodgkin lymphoma with variable clinical outcomes. The immunogenotypic features of this heterogeneous disease in Malaysia were not well characterized.

    MATERIALS & METHODS: In total 141 local series of DLBCL cases from UKM Medical Centre were retrospectively studied.

    RESULTS: Of these cases, we classified our patients into two subtypes: 32.7% (37/113) GCB and non-GCB 67.3% (76/113) by Hans algorithm and the results showed strong agreement with the results by Choi algorithm (κ = 0.828, P<0.001). Survival analysis indicated significant difference in between GCB and non-GCB subtypes (P=0.01), elevated serum LDH (P=0.016), age more than 60-year-old (P=0.021) and the presence of B symptoms (P=0.04). We observed 12% DLBCL cases were CD5 positive and 81.8% of them died of the disease (P=0.076). Analysis on the dual expression of MYC/BCL2 revealed that there is no significant difference in DE and non-DE groups (P=0.916). FISH study reported there were 9.22% (13/141) rearranged cases observed in our population at which highest frequency of BCL6 gene rearrangement (76.9%), followed by MYC (15.4%) and BCL2 (7.7%); no BCL10 and MALT-1 gene rearrangement found regardless of using TMAs or whole tissue samples. More cases of MYC protein overexpression observed compared to MYC translocation.

    CONCLUSION: Relatively lower frequency of GCB tumours and low gene rearrangement rates were observed in Malaysian population. A national study is therefore warranted to know better the immunogenotypic characteristics of DLBCL in Malaysia and their implications on the survival.

  3. Hashim M, Tizen NMS, Alfian N, Hashim H, Nawi AM, Pauzi SHM
    Pan Afr Med J, 2021;38:200.
    PMID: 33995806 DOI: 10.11604/pamj.2021.38.200.19978
    Introduction: endometrial carcinoma (EC) is the seventh most common cancer in females in Malaysia, of which the majority is composed of lower grade type I EC. Although less prevalent, type II EC which is of higher grade has poorer outcome and prognosis. Human epidermal growth factor receptor 2 (HER2) is one of the possible prognostic molecular markers which can be a target for immunotherapy. This study aimed to assess the expression of HER2 in common type of EC in the local population and to determine its correlation with the clinicopathological features.

    Methods: a total of 53 cases of endometrioid type of EC were selected within a six-year period comprising of 22 cases of grade 1, 25 cases of grade 2 and six cases of grade 3 carcinoma. The selected whole tumour tissue sections were immune-stained with HER2 antibody. The scoring was semi-quantitatively analyzed based on 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAPs) guidelines for the scoring of HER2 in breast cancer.

    Results: all cases regardless of grades of endometrioid carcinoma showed negative expression of HER2 (score 0).

    Conclusion: there was no significant HER2 expression in endometrioid carcinoma. However, a follow-up study with a larger number of samples from different type of endometrial carcinoma is needed. Testing of several tumour tissue blocks to assess possible tumour heterogeneity, as well as correlation with HER2 gene amplification status by in-situ-hybridisation, are also recommended.

  4. Affandi KA, Tizen NMS, Mustangin M, Zin RRMRM
    J Pathol Transl Med, 2018 Sep;52(5):283-289.
    PMID: 30235512 DOI: 10.4132/jptm.2018.08.14
    BACKGROUND: Lung cancer is the third most common cancer worldwide. With major advances in the molecular testing of lung cancers and the introduction of targeted therapies, the distinction between adenocarcinoma and squamous cell carcinoma as well as pathologic subtyping has become important. Recent studies showed that p40 is highly specific for squamous and basal cells and is superior to p63 for diagnosing lung squamous cell carcinoma. The aim of this study was to evaluate the use of p40 immunohistochemical stain in the diagnosis of non-small cell lung carcinoma and its potential to replace current p63 antibody as the best immunohistochemical squamous marker.

    METHODS: Seventy formalin-fixed paraffin-embedded cases previously diagnosed as primary lung squamous cell carcinoma (n = 35) and lung adenocarcinoma (n = 35) from January 2008 to December 2016 were retrieved. The results of tumour cell immunoreactivity for p40 and p63 antibodies in lung squamous cell carcinoma and lung adenocarcinoma were compared.

    RESULTS: p40 was expressed in 27 cases of lung squamous cell carcinoma (77.1%). All cases of lung adenocarcinoma (35/35, 100%) were negative for p40. p63 expression was positive in 30 cases of lung squamous cell carcinoma (85.7%) and 13 cases of lung adenocarcinoma (37.1%). Reactivity for both p40 and p63 in lung squamous cell carcinoma was strong and diffuse, whereas variable reactivity was observed in lung adenocarcinoma.

    CONCLUSIONS: p40 is an excellent marker for distinguishing lung squamous cell carcinoma from adenocarcinoma, and p40 expression is equivalent to p63 expression in lung squamous cell carcinoma.

  5. Phang KC, Akhter A, Tizen NMS, Rahman FA, Zahratul Azma R, Elyamany G, et al.
    J Clin Pathol, 2018 Mar;71(3):215-220.
    PMID: 28775174 DOI: 10.1136/jclinpath-2017-204548
    AIMS: The cell of origin (COO) based molecular characterisation into germinal centre B-cell-like (GCB) and activated B-cell-like (ABC) subtypes are central to the pathogenesis and clinical course in diffuse large B-cell lymphoma (DLBCL). Globally, clinical laboratories employ pragmatic but less than ideal immunohistochemical (IHC) assay for COO classification. Novel RNA-based platforms using routine pathology samples are emerging as new gold standard and offer unique opportunities for assay standardisation for laboratories across the world. We evaluated our IHC protocols against RNA-based technologies to determine concordance; additionally, we gauged the impact of preanalytical variation on the performance of Lymph2Cx assay.

    METHODS: Diagnostic biopsies (n=104) were examined for COO classification, employing automated RNA digital quantification assay (Lymph2Cx). Results were equated against IHC-based COO categorisation. Assay performance was assessed through its impact on overall survival (OS).

    RESULTS: 96 (92%) informative samples were labelled as GCB (38/96; 40%) and non-GCB (58/96; 60%) by IHC evaluation. Lymph2Cx catalogued 36/96 (37%) samples as GCB, 45/96 (47%) as ABC and 15/96 (16%) as unclassified. Lymph2Cx being reference, IHC protocol revealed sensitivity of 81% for ABC and 75% for GCB categorisation and positive predictive value of 81% versus 82%, respectively. Lymph2Cx-based COO classification performed superior to Hans algorithm in predicting OS (log rank test, p=0.017 vs p=0.212).

    CONCLUSIONS: Our report show that current IHC-based protocols for COO classification of DLBCL at UKM Malaysia are in line with previously reported results and marked variation in preanalytical factors do not critically impact Lymph2Cx assay quality.

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