Displaying publications 1 - 20 of 43 in total

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  1. Kaewput C, Suppiah S, Vinjamuri S
    World J Nucl Med, 2018 Jan-Mar;17(1):34-40.
    PMID: 29398963 DOI: 10.4103/wjnm.WJNM_16_17
    The aim of our study was to correlate tumor uptake of 68Ga-DOTA-NOC positron emission tomography/computed tomography (PET/CT) with the pathological grade of neuroendocrine tumors (NETs). 68Ga-DOTA-NOC PET/CT examinations in 41 patients with histopathologically proven NETs were included in the study. Maximum standardized uptake value (SUVmax) and averaged SUV SUVmean of "main tumor lesions" were calculated for quantitative analyses after background subtraction. Uptake on main tumor lesions was compared and correlated with the tumor histological grade based on Ki-67 index and pathological differentiation. Classification was performed into three grades according to Ki-67 levels; low grade: Ki-67 <2, intermediate grade: Ki-67 3-20, and high grade: Ki-67 >20. Pathological differentiation was graded into well- and poorly differentiated groups. The values were compared and evaluated for correlation and agreement between the two parameters was performed. Our study revealed negatively fair agreement between SUVmax of tumor and Ki-67 index (r = -0.241) and negatively poor agreement between SUVmean of tumor and Ki-67 index (r = -0.094). SUVmax of low-grade, intermediate-grade, and high-grade Ki-67 index is 26.18 ± 14.56, 30.71 ± 24.44, and 6.60 ± 4.59, respectively. Meanwhile, SUVmean of low-grade, intermediate-grade, and high-grade Ki-67 is 8.92 ± 7.15, 9.09 ± 5.18, and 3.00 ± 1.38, respectively. As expected, there was statistically significant decreased SUVmax and SUVmean in high-grade tumors (poorly differentiated NETs) as compared with low- and intermediate-grade tumors (well-differentiated NETs). SUV of 68Ga-DOTA-NOC PET/CT is not correlated with histological grade of NETs. However, there was statistically significant decreased tumor uptake of 68Ga-DOTA-NOC in poorly differentiated NETs as compared with the well-differentiated group. As a result of this pilot study, we confirm that the lower tumor uptake of 68Ga-DOTA-NOC may be associated with aggressive behavior and may, therefore, result in poor prognosis.
    Matched MeSH terms: Ki-67 Antigen
  2. Cheah PL, Looi LM, Nazarina AR, Mun KS, Goh KL
    Malays J Pathol, 2008 Dec;30(2):103-7.
    PMID: 19291919 MyJurnal
    Transaminase enzymes, alanine (ALT) and aspartate transaminase (AST), have been reported to be raised and implicated to have prognostic value in hepatocellular carcinoma (HCC). Ki67, a marker of cellular proliferative activity, has also been noted to be increased in HCC. A study was conducted at the Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur to determine the possible association of proliferative activity, as determined by Ki67, with the transaminase enzymes. 31 cases of histologically diagnosed HCC who underwent tumour resection were retrieved from departmental archives. The patients' ages ranged between 40 to 79 years with a mean of 58.3 years. There was a male preponderance with M:F = 2.9:1. Ethnic Chinese formed 83.9% of the cases. 4 microm sections, cut from the formalin-fixed, paraffin-embedded tumour tissue block of each case, were immunohistochemically stained with Ki67 (DAKO monoclonal MIB-1) using the commercial DakoCytomation EnVision+System-HRP kit. The latest ALT and AST levels, assayed within 7 days prior to tumour resection, were retrieved from the patients' case records. 24 (77.4%) HCC demonstrated elevation of either ALT and/or AST. 27 (87.1%) HCC were immunopositive for Ki67. Ki67 immunoexpression was significantly correlated with raised transaminases (p<0.05). Hypothetically, the mechanism by which this phenomenon may occur may simply be release of transaminases due to destruction of hepatocytes by the cancer. Thus rising levels of the transaminases could signal a more rapid growth of the tumour and these routinely performed tests can be of prognostic value in management of HCC patients.
    Matched MeSH terms: Ki-67 Antigen/biosynthesis*
  3. Cheah PL, Kunaseegaran R, Looi LM
    Malays J Pathol, 2001 Jun;23(1):27-30.
    PMID: 16329544
    Ki-67 expression in diffuse proliferative lupus nephritis, WHO Class IV, was compared against normal controls to establish that cellular proliferation is involved in the production of glomerular hypercellularity. Twenty-three histologically confirmed WHO Class IV lupus nephritis and 23 normal control renal tissue were immunohistochemically stained with a polyclonal antibody to Ki-67 (Dako) using the peroxidase labelled streptavidin bioitin kit (Dako). There were 20 females and 3 males, with 17 Chinese and 6 Malays in the WHO Class IV lupus nephritis group. Ages of patients ranged between 10-56 years with a mean of 31.9 years. The normal controls, 20 males and 3 females, and ethnically 9 Indians, 7 Malays, 2 Chinese, and 5 foreign nationals (4 Indonesians and 1 Bangladeshi), had an age range between 15-33 years (mean = 23.3 years). Sixteen (69.6%) WHO Class IV lupus nephritis and 8 (34.8%) normal controls demonstrated Ki-67 immunoreactivity in at least 1 glomerulus (p<0.05). Of the 256 WHO Class IV lupus nephritis non-sclerosed, glomeruli studied, 37 (14.5%) were Ki-67 immunopositive compared with normal controls where 16 (0.7%) of 2159 glomeruli demonstrated Ki-67 (p< 0.01). Cellular proliferative activity, as evidenced by Ki-67 expression, was significantly increased in WHO Class IV lupus nephritis confirming that cell proliferation contributes to glomerular hypercellularity.
    Matched MeSH terms: Ki-67 Antigen/metabolism*
  4. Yip Ch, Bhoo-Pathy N, Daniel J, Foo Y, Mohamed A, Abdullah M, et al.
    Asian Pac J Cancer Prev, 2016;17(3):1077-82.
    PMID: 27039727
    BACKGROUND: The three standard biomarkers used in breast cancer are the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The Ki-67 index, a proliferative marker, has been shown to be associated with a poorer outcome, and despite absence of standardization of pathological assessment, is widely used for therapy decision making. We aim to study the role of the Ki-67 index in a group of Asian women with breast cancer.

    MATERIALS AND METHODS: A total of 450 women newly diagnosed with Stage 1 to 3 invasive breast cancer in a single centre from July 2013 to Dec 2014 were included in this study. Univariable and multivariable logistic regression was used to determine the association between Ki-67 (positive defined as 14% and above) and age, ethnicity, grade, mitotic index, ER, PR, HER2, lymph node status and size. All analyses were performed using SPSS Version 22.

    RESULTS: In univariable analysis, Ki -67 index was associated with younger age, higher grade, ER and PR negativity, HER2 positivity, high mitotic index and positive lymph nodes. However on multivariable analysis only tumour size, grade, PR and HER2 remained significant. Out of 102 stage 1 patients who had ER positive/PR positive/HER2 negative tumours and non-grade 3, only 5 (4.9%) had a positive Ki-67 index and may have been offered chemotherapy. However, it is interesting to note that none of these patients received chemotherapy.

    CONCLUSIONS: Information on Ki67 would have potentially changed management in an insignificant proportion of patients with stage 1 breast cancer.

    Matched MeSH terms: Ki-67 Antigen/metabolism*
  5. Wang PL, Peh SC
    Malays J Pathol, 1997 Jun;19(1):59-64.
    PMID: 10879243
    The International Working Formulation divides non-Hodgkin's lymphoma (NHL) into three grades: low, intermediate and high. This grading system implies rate of tumour growth and hence prognosis. Ki-67 antigen is a proliferation-related nuclear antigen and bcl-2 oncogene product is known to inhibit apoptosis. This study aimed to determine the pattern of expression of Ki-67 antigen and bcl-2 oncoprotein in various grades of NHL. Paraffin-embedded tissues from 42 cases of NHL (7 low, 15 intermediate, 20 high grade) were retrieved from the files of the Department of Pathology, University of Malaya. Ki-67 antigen and bcl-2 oncoprotein were detected using immunohistochemistry. The percentage of positively stained neoplastic cells was determined by semi-quantitative estimation and given scores ranging from 0 to 6. Partition chi square test demonstrated the association of Ki-67 antigen expression and histological grade (p = 0.007). There was no significant difference in Ki-67 antigen expression between intermediate and high grade malignant lymphomas (p = 0.28), whereas significant difference was demonstrated between low and intermediate/high grade tumours (p = 0.003). Bcl-2 oncoprotein expression in the neoplastic cells varied widely within the three histological grades. Statistical analysis showed no association between the expression of bcl-2 oncoprotein and histological grade (p = 0.25). Ki-67 immunostaining is therefore a useful adjunct to histological grading of NHL.
    Matched MeSH terms: Ki-67 Antigen/metabolism*
  6. 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.

    Matched MeSH terms: Ki-67 Antigen/metabolism*
  7. Ismail FW, Shamsudin AM, Wan Z, Daud SM, Samarendra MS
    J Exp Clin Cancer Res, 2010 Mar 12;29(1):25.
    PMID: 20226047 DOI: 10.1186/1756-9966-29-25
    BACKGROUND: Giant cell tumor is an infrequent and unpredictable bony lesion. Although numerous attempts have been made to predict the behaviour of GCT, there are no definite biological or histological parameters to determine the prognosis or aggressiveness of this lesion

    MATERIALS AND METHODS: We analyzed Ki 67 immuno-histochemistry of 31 consecutive cases staged III giant cell tumor to determine the clinico-pathological correlation. There were 19 male patients compare to 12 females. The mean age was 33.8 years ranged from 18 to 59 years. Five cases presented with local recurrence prior to wide resection and one case had multiple recurrences there after. Six cases had pulmonary metastases. Expression of Ki 67 antigen was evaluated by immuno-histochemical staining techniques using the avidin-biotin perioxidase complex method using an LSAB2 kit (Dako, Glostrup, Denmark). The primary antibody used in this study was Ki-67 (MIB-I clone, dilution 1:25; Dako).

    RESULTS: The mean value of Ki-67 index obtained as a percentage of 1000 background cells was 8.15 (ranged 1.00 - 20.0). The median Ki 67 index was 7.5 with standard deviation of 5.12. The Ki 67 index of recurrence tumor was 4.323 compared to 6.05 without recurrence and was not statistically significant (mean difference of 0.865 with p value in independent t test of 0.736). The Ki 67 index was also not statistically significant in the presence of pulmonary metastases with the mean value of metastases group of 6.681 compared to 2.890 without metastases (mean difference of 1.895 with p value in independent t test of 0.424).

    CONCLUSION: Ki 67 index is not use-full prognostic marker for aggressive type of giant cell tumor of the bone.

    Matched MeSH terms: Ki-67 Antigen/analysis*
  8. Yehya AHS, Subramaniam AV, Asif M, Kaur G, Abdul Majid AMS, Oon CE
    World J Gastroenterol, 2022 Aug 28;28(32):4620-4634.
    PMID: 36157930 DOI: 10.3748/wjg.v28.i32.4620
    BACKGROUND: Pancreatic cancer is the most aggressive cancer type. Gemcitabine is the first line chemo-drug used for pancreatic cancer but exerts a broad spectrum of organ toxicities and adverse effects in patients.

    AIM: To evaluate the anti-tumour activity and toxicological effects of Orthosiphon stamineus extract formulation (ID: C5EOSEW5050ESA trademarked as Nuva-staticTM), and gemcitabine combination on pancreatic xenograft model.

    METHODS: Mice were randomly divided into six groups of 6 mice each (n = 6) and given different treatments for 28 d. The study design consisted of a 2 x 3 factorial treatment structure, with gemcitabine (yes/no) by oral (at 1200 and 400 mg/kg per day). Human pancreatic cancer cells were injected subcutaneously into the flanks of athymic nude mice. C5EOSEW5050ESA (200 or 400 mg/kg per day) was administered orally, while gemcitabine (10 mg/kg per 3 d) was given intraperitoneally either alone or in combination treatment. Histopathological analyses of vital organs, tumour tissues, and incidence of lethality were analysed. Analyses of tumour necrosis and proliferation were determined by haematoxylin-eosin staining and immunohistochemistry for Ki-67, respectively.

    RESULTS: No signs of toxicity or damage to vital organs were observed in all treatment groups compared to the untreated group. C5EOSEW5050ESA at 200 mg/kg and gemcitabine combination had no additive antitumor effects compared to a single treatment. Remarkably, a comparably greater response in a reduction in tumour growth, Ki-67 protein expression, and necrosis was demonstrated by 400 mg/kg of C5EOSEW5050ESA and gemcitabine combination than that of the individual agents.

    CONCLUSION: These results highlighted the synergistic activity of C5EOSEW5050ESA with gemcitabine to reduce pancreatic tumour growth in mice compared to a single treatment. Thus, this study provides valuable insights into using C5EOSEW5050ESA as a complementary treatment with gemcitabine for pancreatic cancer.

    Matched MeSH terms: Ki-67 Antigen/metabolism
  9. Mohd Yunus MH, Rashidbenam Z, Fauzi MB, Bt Hj Idrus R, Bin Saim A
    Molecules, 2021 Nov 06;26(21).
    PMID: 34771136 DOI: 10.3390/molecules26216724
    The normal function of the airway epithelium is vital for the host's well-being. Conditions that might compromise the structure and functionality of the airway epithelium include congenital tracheal anomalies, infection, trauma and post-intubation injuries. Recently, the onset of COVID-19 and its complications in managing respiratory failure further intensified the need for tracheal tissue replacement. Thus far, plenty of naturally derived, synthetic or allogeneic materials have been studied for their applicability in tracheal tissue replacement. However, a reliable tracheal replacement material is missing. Therefore, this study used a tissue engineering approach for constructing tracheal tissue. Human respiratory epithelial cells (RECs) were isolated from nasal turbinate, and the cells were incorporated into a calcium chloride-polymerized human blood plasma to form a human tissue respiratory epithelial construct (HTREC). The quality of HTREC in vitro, focusing on the cellular proliferation, differentiation and distribution of the RECs, was examined using histological, gene expression and immunocytochemical analysis. Histological analysis showed a homogenous distribution of RECs within the HTREC, with increased proliferation of the residing RECs within 4 days of investigation. Gene expression analysis revealed a significant increase (p < 0.05) in gene expression level of proliferative and respiratory epithelial-specific markers Ki67 and MUC5B, respectively, within 4 days of investigation. Immunohistochemical analysis also confirmed the expression of Ki67 and MUC5AC markers in residing RECs within the HTREC. The findings show that calcium chloride-polymerized human blood plasma is a suitable material, which supports viability, proliferation and mucin secreting phenotype of RECs, and this suggests that HTREC can be a potential candidate for respiratory epithelial tissue reconstruction.
    Matched MeSH terms: Ki-67 Antigen/analysis; Ki-67 Antigen/genetics
  10. Zulfahmi Said, Hellen Colley, Craig Murdoch
    MyJurnal
    Introduction: Tissue-engineered oral mucosa (TEOM) is increasingly being used to model oral mucosal diseases and to assess drug toxicity. Current TEOM models are constructed using normal oral fibroblasts (NOF) contained within a hydrogel matrix with normal oral keratinocytes (NOK) cultured on top. NOK are not commercially available and suffer from donor-to-donor variability. Therefore, oral mucosal models based on immortalised keratinocytes may offer advantages over NOK-based models. The objective of this study was to construct and characterise the TEOM developed using TERT2-immortalised oral keratinocyte (FNB6) cells and validate its similarity to normal oral muco-sal tissue. Methods: TEOM were constructed by culturing FNB6 cells on top of a NOF-populated collagen type-1 hydrogel in tissue culture transwell inserts cultured at an air-to-liquid interface and collected at 14 day. TEOM were subjected to morphological (H&E and PAS), ultrastructural (TEM) and immunohistological (Ki-67, cytokeratin 14 and E-cadherin) analysis. Results: Histologically TEOM mimicked native oral mucosa displaying a stratified epithelium, fibroblast-containing connective tissue and basement membrane. Furthermore, TEM confirmed the presence of des-mosomes and hemi-desmosomes in the epithelium. IHC revealed expression of differentiation markers (cytokeratin 14), proliferation (Ki-67), cell adhesion (E-cadherin). Conclusion: FNB6 mucosal models able to mimic native oral mucosa structure. It has potential for drug delivery and toxicity evaluation, and replacing models based on NOK where access to primary cells is limited.
    Matched MeSH terms: Ki-67 Antigen
  11. Zhang Y, Lee SH, Wang C, Gao Y, Li J, Xu W
    Jpn J Clin Oncol, 2020 Jun 24.
    PMID: 32579167 DOI: 10.1093/jjco/hyaa089
    BACKGROUND: Patient-derived xenograft model is a powerful and promising tool for drug discovery and cancer biology studies. The application of previous metastatic colorectal cancer models has been greatly limited by its low success rate and long time to develop metastasis. Therefore, in this study, we aim to describe an optimized protocol for faster establishment of colorectal cancer metastatic patient-derived xenograft mouse models.

    METHODS: Smaller micro tissues (˂150 μm in diameter) mixed with Matrigel were engrafted subcutaneously into NSG mice to generate the passage 1 (P1) patient-derived xenograft. The micro tumours from P1 patient-derived xenograft were then excised and orthotopically xenografted into another batch of NSG mice to generate a metastatic colorectal cancer patient-derived xenograft, P2. Haematoxylin and eosin and immunohistochemistry staining were performed to compare the characters between patient-derived xenograft tumours and primary tumours.

    RESULTS: About 16 out of 18 P1 xenograft models successfully grew a tumour for 50.8 ± 5.1 days (success rate 89.9%). Six out of eight P1 xenograft models originating from metastatic patients successfully grew tumours in the colon and metastasized to liver or lung in the NSG recipients for 60.9 ± 4.5 days (success rate 75%). Histological examination of both P1 and P2 xenografts closely resembled the histological architecture of the original patients' tumours. Immunohistochemical analysis revealed similar biomarker expression levels, including CDH17, Ki-67, active β-catenin, Ki-67 and α smooth muscle actin when compared with the original patients' tumours. The stromal components that support the growth of patient-derived xenograft tumours were of murine origin.

    CONCLUSIONS: Metastatic patient-derived xenograft mouse model could be established with shorter time and higher success rate. Although the patient-derived xenograft tumours were supported by the stromal cells of murine origin, they retained the dominant characters of the original patient tumours.

    Matched MeSH terms: Ki-67 Antigen
  12. Wong Y, Abdul-Rahman F, Samsudin AT, Masir N
    Malays J Pathol, 2014 Aug;36(2):125-9.
    PMID: 25194535 MyJurnal
    Follicular lymphoma is characterised by the t(14;18)(q32;q21) chromosomal translocation causing BCL2 protein overexpression. A proportion of follicular lymphomas do not carry the t(14;18) translocation and lacked BCL2 protein expression. We describe a case of a BCL2 protein- and t(14;18)-negative follicular lymphoma that caused diagnostic difficulty. The usefulness of several immunomarkers including Ki67, CD79a and CD21 in aiding the diagnosis is discussed. The patient is a 51-year-old male who presented with gradually enlarging lymphadenopathy. Histopathological examination of the lymph node showed complete architectural effacement by neoplastic follicles containing expanded CD21-positive follicular dendritic cell meshwork. The neoplastic cells expressed pan-B cell markers (CD20, CD79a) and germinal centre marker (BCL6) but not BCL2 and CD10. Of interest are the staining patterns of Ki67 and CD79a. We observed that the Ki67- positive proliferating cells were evenly distributed within the neoplastic follicles without zonation. In addition, CD79a was homogeneously strong within the neoplastic follicles. These staining patterns were distinctly different from that observed in reactive lymphoid follicles. Fluorescent insitu hybridisation (FISH) analysis however showed absence of BCL2 gene rearrangement. Despite the atypical immunophenotype and lack of BCL2 gene rearrangement, the diagnosis of follicular lymphoma was made based on careful observation of the morphology as well as immunoarchitecture of the Ki67, CD79a and CD21 markers.
    Matched MeSH terms: Ki-67 Antigen/metabolism*
  13. Mdpaiman N, Md Ali SA, Mdzin R, Meor Kamal MZ, Md Amin WA, Nallusamy M, et al.
    PLoS One, 2014;9(2):e89172.
    PMID: 24586570 DOI: 10.1371/journal.pone.0089172
    Breast cancer estrogen receptor (ER) status is one of the strong additional factors in predicting response of patients towards hormonal treatment. The main aim of this study was to assess the morphological characteristics and proliferative activity using MIB-1(Ki-67) of estrogen receptor negative invasive breast ductal carcinoma (NOS type) as well as to correlate these features with clinicopathological data. We also aim to study the expression of c-erbB2 in ER negative breast tumors. High proliferative rate (MIB-1 above 20%) was observed in 63 (63.6%) of 99 ER negative tumors and that these tumors were associated with high expression of c-erbB2 (57.6%). We observed that MIB-1 is a reliable independent prognostic indicator for ER negative infiltrating ductal carcinoma in this study.
    Matched MeSH terms: Ki-67 Antigen/metabolism*
  14. Yahaya B, Baker A, Tennant P, Smith SH, Shaw DJ, McLachlan G, et al.
    Exp. Lung Res., 2011 Nov;37(9):519-35.
    PMID: 21895444 DOI: 10.3109/01902148.2011.605513
    Understanding the fundamental processes involved in repairing the airway wall following injury is fundamental to understanding the way in which these processes are perturbed during disease pathology. Indeed complex diseases such as asthma and chronic obstructive pulmonary disease (COPD) have at their core evidence of airway wall remodeling processes that play a crucial functional role in these diseases. The authors sought to understand the dynamic cellular events that occur during bronchial airway epithelial repair in sheep. The injury was induced by endobronchial brush biopsy (BBr), a process that causes epithelial débridement and induces a consequential repair process. In addition, the current experimental protocol allowed for the time-dependent changes in airway wall morphology to be studied both within and between animals. The initial débridement was followed by evidence of dedifferentiation in the intact epithelium at the wound margins, followed by proliferation of cells both within the epithelium and in the deeper wall structures, notably in association with the submucosal glands and smooth muscle bundles. Seven days after injury, although the airway wall was thickened at the site of damage, the epithelial layer was intact, with evidence of redifferentiation. These studies, in demonstrating broad agreement with previous studies in small animals, indicate the wider relevance of this system as a comparative model and should provide a solid basis upon which to further characterize the critical cellular and molecular interactions that underlie both effective restitution and pathological repair.
    Matched MeSH terms: Ki-67 Antigen/metabolism
  15. Alomari YM, Sheikh Abdullah SN, MdZin RR, Omar K
    Comput Math Methods Med, 2015;2015:673658.
    PMID: 25793010 DOI: 10.1155/2015/673658
    Analysis of whole-slide tissue for digital pathology images has been clinically approved to provide a second opinion to pathologists. Localization of focus points from Ki-67-stained histopathology whole-slide tissue microscopic images is considered the first step in the process of proliferation rate estimation. Pathologists use eye pooling or eagle-view techniques to localize the highly stained cell-concentrated regions from the whole slide under microscope, which is called focus-point regions. This procedure leads to a high variety of interpersonal observations and time consuming, tedious work and causes inaccurate findings. The localization of focus-point regions can be addressed as a clustering problem. This paper aims to automate the localization of focus-point regions from whole-slide images using the random patch probabilistic density method. Unlike other clustering methods, random patch probabilistic density method can adaptively localize focus-point regions without predetermining the number of clusters. The proposed method was compared with the k-means and fuzzy c-means clustering methods. Our proposed method achieves a good performance, when the results were evaluated by three expert pathologists. The proposed method achieves an average false-positive rate of 0.84% for the focus-point region localization error. Moreover, regarding RPPD used to localize tissue from whole-slide images, 228 whole-slide images have been tested; 97.3% localization accuracy was achieved.
    Matched MeSH terms: Ki-67 Antigen/metabolism*
  16. Govindaraj PK, Kallarakkal TG, Mohd Zain R, Tilakaratne WM, Lew HL
    PLoS One, 2021;16(12):e0261575.
    PMID: 34941961 DOI: 10.1371/journal.pone.0261575
    BACKGROUND: Local relapse of oral squamous cell carcinoma in non-involved mucosal surgical margins indicated possibility of field alteration in the margins, which could be predicted with certain biomarkers. The objectives were to evaluate the expression of Ki-67, Cornulin and ISG15 in non-involved mucosal surgical margins and the association of clinicopathological prognosticators with local relapse in oral squamous cell carcinoma.

    METHODS: Surgical margins from the study (relapse) group (n = 23), control (non-relapse) group (n = 32) and normal oral mucosa (n = 5) were immunohistochemically stained using Ki-67, Cornulin and ISG15 antibodies. Association between expression of markers and clinicopathological prognosticators with local relapse in oral squamous cell carcinoma was analyzed statistically.

    RESULTS: The study group surgical margins demonstrated significantly decreased Cornulin expression (p = 0.032). Low Cornulin expression was significantly associated with local relapse (p = 0.004) and non-tongue primary tumor (p = 0.013). Although not significantly associated with local relapse, expression of Ki-67 was significantly reduced in female patients (p = 0.041). Age above 57.5 years, Chinese & Indian ethnicity, alcohol consumption, epithelial dysplasia in surgical margins, and type III and IV patterns of invasion of tumor were also significantly related to local relapse. Regression analysis showed low expression of Cornulin (p = 0.018), and increased patient's age (p = 0.008) were predictors of local relapse in oral squamous cell carcinoma, with 34-fold risk and 18-fold risk, respectively. Expression of Ki-67 and ISG15 did not show significant association with local relapse in oral squamous cell carcinoma.

    CONCLUSION: Low expression of Cornulin is an independent predictor of relapse in oral squamous cell carcinoma.

    Matched MeSH terms: Ki-67 Antigen/analysis*
  17. Mohd Ali NA, Nasaruddin AF, Mohamed SS, Wan Rahman WF
    Asian Pac J Cancer Prev, 2020 Sep 01;21(9):2653-2659.
    PMID: 32986365 DOI: 10.31557/APJCP.2020.21.9.2653
    OBJECTIVE: Phyllodes tumour (PT) is a rare fibroepithelial neoplasm of the breast that carries a risk of malignancy. Histopathological examination remains a gold standard for diagnosis. The usage of the immunohistochemical markers of Ki67 and p53 acts as a supplement method, particularly for the malignant PT. We aim here to study the expression of these markers in PT and to see their relation to the tumour grading.

    METHODOLOGY: We conducted a retrospective cross-sectional study on 57 archived formalin-fixed paraffin-embedded tissue blocks of PT from the years 2015 to 2018 from two hospitals in East Coast Malaysia. The histopathological examination and immunohistochemical stain for Ki67 and p53 were analysed.

    RESULTS: There was an association between clinical descriptive data of skin changes, lump size of more than 3 cm, cytological atypia, stromal hypercellularity, mitosis and immunohistochemistry with the clinical diagnosis of PT. Both marked expression of Ki67 and p53 were seen in borderline and malignant PT. Our study showed that in the presence of high mitotic figures, marked expression of Ki67 was only seen in cases of malignant PT.

    CONCLUSION: We found a significant association of Ki67 and p53 expressions, high mitosis and other descriptive histopathological features in malignant PT. Further study with larger sample size is recommended to predict tumour grade and prognosis as well as the disease-free survival of the tumour. 
    .

    Matched MeSH terms: Ki-67 Antigen/metabolism*
  18. Seow HF, Yip WK, Loh HW, Ithnin H, Por P, Rohaizak M
    Pathol Oncol Res, 2010 Jun;16(2):239-48.
    PMID: 19882362 DOI: 10.1007/s12253-009-9216-3
    Activation of Akt signaling pathway has been documented in various human malignancies, including breast carcinoma. The objective of this study is to determine the incidence of Akt phosphorylation in breast tumours and its relationship with expression of ER-alpha, ER-beta, HER2, Ki-67 and phosphorylated Bcl-2 associated death domain (p-BAD). Immunohistochemical staining was performed to detect these molecules on 43 paraffin-embedded breast tumour tissues with commercially available antibodies. Eighteen (41.9%), 3 (7.0%), 23 (53.5%), 35 (81.4%), 21 (48.8%), 29 (67.4%), and 34 (81.0%) of breast tumours were positive for nuclear ER-alpha, nuclear ER-beta, membranous HER2, cytonuclear p-Akt (Thr308), p-Akt (Ser473), p-BAD and Ki-67, respectively. ER-alpha expression was inversely correlated with HER2 and Ki-67 (P = 0.041 and P = 0.040, respectively). The p-Akt (Ser473) was correlated with increased level of p-BAD (Ser136) (P = 0.012). No relationship of Akt phosphorylation with HER2, ER-alpha or ER-beta was found. The p-Akt (Ser473) immunoreactivity was significantly higher in stage IV than in stage I or II (P = 0.036 or P = 0.009). The higher Ki-67 and lower ER-alpha expression showed an association with patient age of <50 years (P = 0.004) and with positive nodal status (P = 0.033), respectively. Our data suggest that the Akt phosphorylation and inactivation of its downstream target, BAD may play a role in survival of breast cancer cell. This study does not support the simple model of linear HER2/PI3K/Akt pathway in breast cancer.
    Matched MeSH terms: Ki-67 Antigen/genetics; Ki-67 Antigen/metabolism
  19. Hew CS, Khoo BY, Gam LH
    PLoS One, 2013;8(7):e68524.
    PMID: 23874655 DOI: 10.1371/journal.pone.0068524
    Gynura procumbens (Lour.) Merr. belongs to the Asteraceae Family. The plant is a well-known traditional herb in South East Asia and it is widely used to treat inflammation, kidney discomfort, high cholesterol level, diabetic, cancer and high blood pressure. Our earlier study showed the presence of valuable plant defense proteins, such as peroxidase, thaumatin-like proteins and miraculin in the leaf of G. procumbens. However, the effects of these defense proteins on cancers have never been determined previously. In the present study, we investigated the bioactivity of gel filtration fractionated proteins of G. procumbens leaf extract. The active protein fraction, SN-F11/12, was found to inhibit the growth of a breast cancer cell line, MDA-MB-231, at an EC50 value of 3.8 µg/mL. The mRNA expressions of proliferation markers, Ki67 and PCNA, were reduced significantly in the MDA-MB-23 cells treated with SN-F11/12. The expression of invasion marker, CCL2, was also found reduced in the treated MDA-MB-231 cells. All these findings highlight the anti-cancer property of SN-F11/12, therefore, the proteins in this fraction can be a potential chemotherapeutic agent for breast cancer treatment.
    Matched MeSH terms: Ki-67 Antigen/metabolism
  20. Tan GC, Sharifah NA, Shiran MS, Salwati S, Hatta AZ, Paul-Ng HO
    Asian Pac J Cancer Prev, 2008 Oct-Dec;9(4):781-4.
    PMID: 19256776
    The differentiation between cervical intraepithelial neoplasia 3 (CIN 3) and early squamous cell carcinoma (SCC) of the cervix may be difficult in certain situations. Identification of invasion beyond the basement membrane is the gold standard for the diagnosis of the latter. The objective of this study was to determine whether the use of Ki-67 and p53 could help in solving the above dilemma. This was a retrospective study on 61 cases of cervical neoplasms comprising of 25 cases of CIN 3 and 36 SCC. All cases were evaluated by immunohistochemistry using Ki-67 and p53 monoclonal antibodies. Results showed that the differences of Ki-67 and p53 expression between CIN 3 and SCC were statistically significant. In conclusion, Ki-67 and p53 may serve as helpful adjuncts to routinely-stained histological sections in differentiating between CIN 3 and SCC.
    Matched MeSH terms: Ki-67 Antigen/analysis*
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