Displaying publications 61 - 80 of 93 in total

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  1. Wong YP, Affandi KA, Tan GC, Muhammad R
    Indian J Pathol Microbiol, 2017 9 25;60(3):430-432.
    PMID: 28937391 DOI: 10.4103/IJPM.IJPM_287_16
    Metastatic disease involving the thyroid gland is uncommon. Solitary thyroid metastases from various primary sites particularly kidney, lung, and breast had been previously described. To the best of our knowledge, metastases from two topographically separate primary malignancies to the thyroid have never been documented hitherto. This is the first reported case of cancer-to-cancer metastasis involving an invasive breast carcinoma metastasized within a metastatic renal cell carcinoma in the nonneoplastic thyroid in a 58-year-old woman. Distinguishing a secondary thyroid metastases from a primary thyroid malignancy is utmost crucial as treatment differs. The possibility of tumor metastases from two separated primaries should always be considered in a tumor exhibiting malignant cell populations with two distinctive histomorphological appearances. The role of immunohistochemistry stains in equivocal cases cannot be overemphasized.
    Matched MeSH terms: Biomarkers, Tumor/analysis
  2. Tay TKY, Lim KL, Hilmy MH, Thike AA, Goh ST, Song LH, et al.
    Malays J Pathol, 2017 Dec;39(3):257-265.
    PMID: 29279588
    INTRODUCTION: Human papillomavirus (HPV) testing is used as a means of triaging cervico-vaginal smears with low grade squamous abnormalities or as part of co-testing with cytology. While HPV testing has a high sensitivity, it has a low specificity in detecting cervical intraepithelial neoplasia grade 2 and above (CIN 2+) leading to unnecessary colposcopy referrals. We investigate the accuracy of the p16/Ki-67 dual immunocytochemical stain in determining the presence of CIN 2+ lesions on histology and its potential as a superior biomarker for triage.

    METHODS: Liquid based cervico-vaginal cytology specimens with squamous abnormalities and corresponding histology from 97 women with subsequent colposcopy and biopsy were included. The specimens were then subjected to the dual stain and Roche Cobas 4800 multiplex real time PCR HPV DNA testing. The sensitivity and specificity of the dual stain and HPV testing were calculated using CIN 2+ on histology as a reference standard.

    RESULTS: The sensitivity and specificity of the dual stain in detecting histology proven CIN 2+ was 93.7% and 76.5% while HPV testing was 85.7% and 14.7% respectively. Of the 44 women with ASCUS or LSIL on cytology, the dual stain also reduced the number of unnecessary colposcopy referrals from 27 to 7 when used as a triage marker compared to HPV testing.

    CONCLUSION: p16/Ki-67 dual stain was more sensitive and specific than HPV testing in determining the presence of CIN 2+ on histology. It could triage low grade cervico-vaginal specimens more effectively and potentially help women avoid unnecessary colposcopies. Future studies are needed to further evaluate its role in cervical cancer screening programmes.

    Matched MeSH terms: Biomarkers, Tumor/analysis*
  3. Gomaa W, Al-Ahwal M, Al-Maghrabi H, Buhmeida A, Al-Qahtani M, Al-Maghrabi B, et al.
    Malays J Pathol, 2017 Dec;39(3):243-250.
    PMID: 29279586
    BACKGROUND/AIM: Colorectal carcinoma (CRC) carries a high incidence of morbidity and mortality. Prognosis is related to nodal metastasis and stage. Clusterin is a widely distributed glycoprotein with not yet fully understood functions. Clusterin may be overexpressed in some tumours or under expressed in other tumours. The aim behind this study is to examine the relation of clusterin cytoplasmic immunostaining to tumour characteristics, disease relapse, and survival in CRC.

    MATERIALS AND METHODS: Paraffin blocks of 133 CRCs were retrieved from the Department of Pathology, King Abdulaziz University, Jeddah, Saudi Arabia. Immunostaining was done using antibody to clusterin. Staining expression in 10% of malignant cells was used as a cut-off to determine low immunostaining and high immunostaining. Statistical tests were used to evaluate the association of clusterin immunostaining with clinicopathological parameters.

    RESULTS: Immunohistochemical results showed clusterin low immunostaining in CRC and nodal metastases. No association was found between clusterin immunostaining and tumour grade, age, tumour invasiveness, distant metastases, vascular invasion, nodal metastases, relapse, and survival.

    CONCLUSION: Our study showed low clusterin immunostaining in CRC with lack of association with prognostic indicators in CRC. These results raise the controversy of understanding the role of clusterin in CRC. Further molecular studies are required to explore more about possible mechanisms of clusterin association with tumorigenicity, apoptosis, tumour growth progression, local and vascular invasion, and metastasis of CRC.

    Matched MeSH terms: Biomarkers, Tumor/analysis*
  4. Cheo FF, Sittampalam K
    Malays J Pathol, 2017 Dec;39(3):305-309.
    PMID: 29279595
    Pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma is a rare, low grade vascular (endothelial) neoplasm typically presenting as multicentric, superficial to deep nodules in extremities with a slight tendency of affecting young adult males. We report a case of pseudomyogenic hemangioendothelioma in a 15-year-old boy presenting initially with a 1 cm right thigh painless cutaneous lump. The lump was excised with the clinical impression of a sebaceous cyst. On microscopy, a poorly circumscribed, mild to moderately atypical spindle cell lesion in fascicular and storiform patterns with strikingly myoid-like eosinophilic cytoplasm was identified. The spindle cells were highlighted by pancytokeratin AE1/AE3, CD31, and ERG with retained INI-1, while being negative for MNF116, S100, CD34, EMA, desmin, SMA, caldesmon, myogenin, MyoD1, HHV-8 and CD163. Following the first diagnostic report, a positron emission tomography-computed tomography (PET-CT) scan revealed another 4 cm ill-defined nodule accompanied by a smaller adjacent 0.7 cm ipsilateral satellite nodule within the right psoas muscle that displayed similar morphology and immunophenotype as the cutaneous lump, supporting the multicentric feature of this unique entity. It is an uncommon yet increasingly recognised neoplasm of endothelial origin possessing a misleading myoid morphology and distinctive immunophenotype worth notifying.
    Matched MeSH terms: Biomarkers, Tumor/analysis
  5. Shi R, Chew MH, Leow WQ
    Malays J Pathol, 2017 Dec;39(3):293-296.
    PMID: 29279593
    Gastrointestinal stromal tumour (GIST) is a common mesenchymal tumour arising in the gastrointestinal tract, but not frequently encountered in the rectum. Herein, we describe a case of a rectal GIST which mimicked histomorphological features of a schwannoma; thus, making intraoperative frozen section evaluation challenging. Although subsequent immunohistochemistry and molecular findings readily confirmed the diagnosis of a GIST, we wish to draw attention to three clues that will help the pathologist steer clear of this potential diagnostic pitfall. One, GISTs are relatively more common than schwannomas in the rectum. Two, schwannomas usually have very little mitoses. Three, rectal GISTs commonly exhibit nuclear palisades. We also discuss the diagnostic, prognostic and therapeutic functions of immunohistochemical and molecular investigations. As the surgical intent for rectal GISTs is for en-bloc excision with wide margins, we surmise that the intraoperative consult should include GIST as a possible differential diagnosis for rectal mesenchymal tumours. In view of the potential for neoadjuvant treatment with imatinib before surgical excision to preserve sphincter function, a multidisciplinary approach is recommended for establishing most effective treatment strategy in these rare complex cases.
    Matched MeSH terms: Biomarkers, Tumor/analysis
  6. Md Akhir MKA, Hussin H, Veerakumarasivam A, Choy CS, Abdullah MA, Abd Ghani F
    Malays J Pathol, 2017 Dec;39(3):227-234.
    PMID: 29279584 MyJurnal
    Urothelial carcinoma is a common malignant neoplasm that has a poor prognosis and a high frequency of recurrence and metastasis. Constant disease surveillance with periodic and long term cystoscopy examination is necessary for management of the disease. However, the monitoring and therapy regimen is expensive, incurring a massive burden to patients and the government. Therefore, the development of specific biomarkers for urothelial carcinoma at an early stage and recurrence detection becomes a priority. Homeobox genes are a family of genes that are involved in tumourigenesis. They might be potential prognostic markers for urothelial carcinoma. The study investigated the expression pattern of NANOG which is one of a homeobox gene in different stages and grades of urothelial carcinoma. NANOG expressions were also correlated with patient demographic factors and clinicopathological parameters. The expression of NANOG in 100 formalin-fixed paraffin-embedded urothelial carcinoma tissues was determined by immunohistochemistry. Immunohistochemistry showed positive expression of NANOG in all specimens with detection in the cytoplasm, nuclei and the nuclear membrane of the cancer cells. The immunohistochemical expression of NANOG increased across stages and grades of the tumour. The expression of NANOG was not significantly associated with demographic factors; gender (p = 0.376), race (p = 0.718) and age (p = 0.058) as well as with most of the clinicopathological parameters; pathological stage (p = 0.144), grade (p = 0.625), lymph node involvement (p = 0.174) and distant metastasis (p = 0.228). However, NANOG expression showed significant correlation with tumour invasion (p = 0.019). We concluded that NANOG might be a potential biomarker for early diagnosis of urothelial carcinoma of the bladder.
    Matched MeSH terms: Biomarkers, Tumor/analysis*
  7. Marutha Muthu AK, Cheah PL, Koh CC, Chew MF, Toh YF, Looi LM
    Malays J Pathol, 2017 Dec;39(3):251-255.
    PMID: 29279587 MyJurnal
    Over the years, adenocarcinoma (ADC), which has a worse prognosis than squamous cell carcinoma (SCC) of the cervix, has shown an increasing trend. Cyclooxygenase-2 (COX2) expression which has been associated with worse prognosis in several solid cancers was studied for its association with SCC and ADC of the cervix. 35 histologically re-confirmed SCC and 35 ADC were immunohistochemically stained for COX2 using a mouse monoclonal antibody to COX2 (1:100; Dako: Clone CX-294) on a Ventana Benchmark XT. The histoscore was computed as intensity of staining, semi-quantitated on a scale of 0-3 with 0 = negative, 1 = weak, 2 = moderate and 3 = strong staining intensity; multiplied by percentage of immunopositivity on a scale of 0-4 with 0 = <1%, 1 = 1-25%, 2 = 26-50%, 3 = 51-75% and 4 = ≥75% of immunopositive tumour cells. Histoscore 1-3/12 was considered as low and ≥4/12 as high COX2 expression. SCC affected Chinese more than Malays, while Malays had more ADC (p = 0.032). Mean age at presentation of SCC (57.5 years) was about a decade later than ADC at 47.9 years (p = 0.002). 30/35 (85.7%) of SCC and 34/35 (97.1%) of ADC expressed COX2. Histoscores of ADC (median = 4.0, IQR = 3.0-6.0) was significantly higher (p = 0.014) than those of SCC (median = 3.0, IQR = 2.0-3.0). High histoscores (≥4/12) were more frequent in ADC (55.9%) compared with SCC (26.7%) (p = 0.018), implicating COX2, either directly or indirectly, as a possible player in influencing the poorer outcome of ADC compared with SCC.
    Matched MeSH terms: Biomarkers, Tumor/analysis*
  8. Kaur M, Verma S, Gupta R, Pant L, Singh S
    Malays J Pathol, 2018 Apr;40(1):57-60.
    PMID: 29704385
    CD10, a transmembrane endopeptidase, has been shown to be lost as an early event in prostate cancer. We aimed at evaluating the pattern of expression of CD10 in various Gleason's grades of prostatic adenocarcinoma in comparison with nodular hyperplasia of prostate. This retrospective study included 30 cases of nodular hyperplasia and 30 of prostatic adenocarcinoma of various Gleason's grades. Immunohistochemical staining for CD10 was performed on all cases and positivity evaluated as percentage of cells as well as location (membranous or cytoplasmic or both). Of prostatic adenocarcinomas, grade 3 was seen in 10 foci, grade 4 in 28 and grade 5 in 22 foci. CD10 positivity in carcinoma was lower than in nodular hyperplasia, with the lowest positivity in grade 5. The pattern of expression of CD10 also changed from membranous in grade 3 to cytoplasmic in grade 5. Loss of CD10 expression appears to be associated with increasing tumour grade in carcinoma prostate and this can potentially be useful in stratification of such patients.
    Matched MeSH terms: Biomarkers, Tumor/analysis*
  9. Muthusamy S, Azhar Sha S, Abdullah Suhaimi SN, Kassim N, Mahasin M, Mohd Saleh MF, et al.
    Malays J Pathol, 2018 Aug;40(2):111-119.
    PMID: 30173227 MyJurnal
    INTRODUCTION: Thyroid cancer is the most common endocrine malignancy with more than 95% originating from follicular epithelial cells. Diagnostic dilemma may arise in occasional cases such as when an encapsulated nodule with a follicular growth pattern exhibits clear nuclei with grooves making it difficult to distinguish a follicular adenoma from encapsulated follicular variant papillary thyroid carcinoma. This study aimed to evaluate the diagnostic utility of an immunohistochemical marker, CD56, to distinguish between benign and malignant thyroid lesions.

    MATERIALS AND METHODS: We retrospectively studied CD56 expression in 54 benign and 54 malignant thyroid lesions using archival formalin fixed paraffin-embedded tissue blocks for the study period from January 2010 to December 2015, diagnosed in a tertiary hospital.

    RESULTS: CD56 was expressed in 52/54 (96.3%) of benign specimens and only 24/54 (44.4%) of malignant ones. The malignant specimens comprised 31 (57.4%) papillary thyroid carcinomas (PTC), 11 (20.3%) follicular carcinomas (FC), seven (13%) medullary thyroid carcinomas (MC), one (1.9%) poorly differentiated carcinoma (PC) and four (7.4%) anaplastic carcinomas (AC). CD56 was not expressed in 28/31 (90.3%) of the PTCs, 1/11 (9.1%) FCs, 1/4 (25%) of ACs while all MCs and the PD were positive. The benign group comprised nodular hyperplasias (29/54), lymphocytic thyroiditis (10/54), follicular adenomas (FA) (14/54) and one hyalinising trabecular tumour. CD56 was expressed in all the benign cases except one FA and one nodular hyperplasia. Thirteen of the 14 FAs were CD56 positive. The difference in expression between benign and malignant tumours was statistically significant as the p value was <0.01.

    CONCLUSION: CD56 is a potentially good immunohistochemical marker for differentiating papillary thyroid carcinoma from other benign follicular lesions of the thyroid especially in differentiating follicular variant PTC from FA in equivocal cases.

    Matched MeSH terms: Biomarkers, Tumor/analysis*
  10. De Los Reyes EVA, Rivera DI, Santos HM, Carlos RM
    Malays J Pathol, 2018 Aug;40(2):175-183.
    PMID: 30173236
    INTRODUCTION: Intracranial teratomas account for 0.5% of all intracranial tumours and 2-4% of intracranial tumours in children. However, in terms of tumours of the pineal area, the exact incidence is not ascertained. Although, it is noted that 50-60% of central nervous system (CNS) germ cell tumours are found in the pineal gland. The degree of difficulty in the sampling of lesions in the pineal gland during biopsy emphasizes the importance of correlating the imaging studies, histopathologic findings, and serum and cerebrospinal fluid (CSF) tumour markers.

    CASE REPORT: This case report is that of a 9-year-old male who presented with frontal headache of eight days, with associated photophobia, nausea and vomiting, and diplopia. Biopsy with intraoperative navigation was done and the specimen was referred for histopathologic evaluation. The biopsy showed findings consistent with a mature teratoma with no histologic findings of an immature component or secondary somatic malignancy. Comparison of the pre-operative and post-operative multiaxial cranial CT scan showed findings that was consistent with a residual lesion. This was correlated with the pre-operative serum tumour markers which showed alpha-fetoprotein of 22.5 ng/mL and beta-HCG of 1.0 mIU/mL(IU/L), and the post-operative tumour markers of the cerebrospinal fluid that showed alpha-fetoprotein of 3.28 ng/mL and beta-HCG of 18.9 mIU/mL (IU/L).

    CONCLUSION: A review of the literature and comparison with current case in relation to the histopathologic, serum and CSF findings, and imaging studies was done to better understand the mechanism of this lesion.

    Matched MeSH terms: Biomarkers, Tumor/analysis
  11. Kumcu E, Unverdi H, Kaymaz E, Oral O, Turkbey D, Hucmenoglu S
    Malays J Pathol, 2018 Aug;40(2):137-142.
    PMID: 30173230
    INTRODUCTION: Breast cancer is still a serious health problem in 21st century and diagnosis, treatment and prognosis of this malignant disease are subject to many research. While cancer research has been focused on tumour cells primarily, recent studies showed that tumour stroma contribute to carcinogenesis as well as tumour cells. Especially fibroblasts adjacent to epithelial tumour cells are not ordinary fibroblasts and play the critical role. Studies showed that these cancer associated fibroblasts (CAFs) have different genetic profile and protein expression. One of the differently expressed molecules recently found is podoplanin. Podoplanin, utilised as a lymphatic endothelial marker, is found to be expressed in CAFs. The aim of this study is to evaluate the relationship between the stromal expression of podoplanin in invasive breast carcinoma and clinicopathological parameters.

    MATERIALS & METHODS: Podoplanin expression was evaluated immunohistochemically in 153 breast cancers. Tumours with ≥ 10% distinct cytoplasmic podoplanin staining in CAFs were considered as positive.

    RESULTS: In 65.3% of analysed tumours, podoplanin expression was found positive in CAFs. According to our results, podoplanin positive CAFs correlated significantly with tumour size (p= 0.012), tumour grade (p= 0.032) and cerbB2 score (p= 0.032).

    DISCUSSION: Our results suggest that podoplanin expression by CAFs could predict poor patient outcome in breast carcinoma.

    Matched MeSH terms: Biomarkers, Tumor/analysis*
  12. Tan JSJ, Ong KC, Ong DBL, Razack A, Lim J, Yunus R, et al.
    Malays J Pathol, 2018 Aug;40(2):103-110.
    PMID: 30173226 MyJurnal
    INTRODUCTION: Prostate cancer is a heterogenous disease and the mechanisms that drive it to behave differently are not well understood. Tumour expression of the ERG oncogene occurs in the majority of patients with prostate cancer in Western studies. This is considered to be oncogenic as ERG acts as a transcription factor to regulate genes involved in tumour proliferation and invasion. In this study we investigated expression of ERG in Malaysian men with prostate cancer.

    METHODS: Tissues were collected from 80 patients with clinically detected prostate cancer and treated with radical prostatectomy. Cases were tested for ERG by immunohistochemistry using the mouse monoclonal antibody EP111. All blocks on 48 cases were tested in order to determine the extent of heterogeneity of ERG expression within individual cases. ERG expression was analysed in relation to patient age, ethnicity and tumour stage and grade.

    RESULTS: Forty-six percent of cases were ERG positive. There was no significant association between ERG and tumour grade or stage. Sixty-nine percent of Indian patients had ERG positive tumours; this was significantly higher (p=0.031) than for Chinese (40%) and Malay (44%) patients. Heterogeneity of ERG expression, in which both positive and negative clones were present, was seen in 35% of evaluated cases. Evaluation by tumour foci showed younger patients had more ERG positive tumour foci than older patients (p=0.01). Indian patients were more likely to have the majority of tumour foci with ERG staining positively, compared to either Chinese or Malay patients (P <0.01).

    CONCLUSION: In this study, tumour expression of ERG was more likely to occur in patients of Indian ethnicity.

    Matched MeSH terms: Biomarkers, Tumor/analysis*
  13. Lee PY, Chin SF, Low TY, Jamal R
    J Proteomics, 2018 09 15;187:93-105.
    PMID: 29953962 DOI: 10.1016/j.jprot.2018.06.014
    Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide. Biomarkers that can facilitate better clinical management of CRC are in high demand to improve patient outcome and to reduce mortality. In this regard, proteomic analysis holds a promising prospect in the hunt of novel biomarkers for CRC and in understanding the mechanisms underlying tumorigenesis. This review aims to provide an overview of the current progress of proteomic research, focusing on discovery and validation of diagnostic biomarkers for CRC. We will summarize the contributions of proteomic strategies to recent discoveries of protein biomarkers for CRC and also briefly discuss the potential and challenges of different proteomic approaches in biomarker discovery and translational applications.
    Matched MeSH terms: Biomarkers, Tumor/analysis*
  14. Naicker MS, Tan GC
    Malays J Pathol, 2018 Dec;40(3):319-323.
    PMID: 30580363
    INTRODUCTION: Clinical decision making becomes difficult when clinical and methodological heterogeneity does not permit synthesis of results of multiple small studies.

    AIM: For studies done in Malaysia, to identity the sample sizes and heterogeneity present in the various studies which used p16 in evaluating lesions of the cervix. To evaluate if it would be possible for a single study to answer the various questions posed by the original authors. To highlight areas where the design features of future studies can be optimised.

    MATERIALS AND METHODS: Various databases were searched using synonyms for p16 AND cervix AND Malaysia. These were assessed for broad conformity to a Diagnostic Test Accuracy format. Methodological and clinical heterogeneity indicators were extracted into standardised fields.

    RESULTS: There were 5 studies eligible for inclusion. Each sought to study different aspects of the disease such as diagnostic grade stratification and pathogenesis. The study type broadly conformed to a Diagnostic Test Accuracy format. The study design used was either consecutive or non-consecutive. Sample size ranged from 75 to 201. Clinical heterogeneity was present in the choice of controls with some using normal and some using inflamed tissue. Methodological heterogeneity in applying the reference test, index test and different antibody clones were present.

    CONCLUSION: There was both clinical and methodological heterogeneity making synthesis of studies difficult. It is possible to design a study which would be able to answer all the questions posed by the original authors with internal validity while at the same time increasing sample size.

    Matched MeSH terms: Biomarkers, Tumor/analysis
  15. Seow P, Wong JHD, Ahmad-Annuar A, Mahajan A, Abdullah NA, Ramli N
    Br J Radiol, 2018 Dec;91(1092):20170930.
    PMID: 29902076 DOI: 10.1259/bjr.20170930
    OBJECTIVE:: The diversity of tumour characteristics among glioma patients, even within same tumour grade, is a big challenge for disease outcome prediction. A possible approach for improved radiological imaging could come from combining information obtained at the molecular level. This review assembles recent evidence highlighting the value of using radiogenomic biomarkers to infer the underlying biology of gliomas and its correlation with imaging features.

    METHODS:: A literature search was done for articles published between 2002 and 2017 on Medline electronic databases. Of 249 titles identified, 38 fulfilled the inclusion criteria, with 14 articles related to quantifiable imaging parameters (heterogeneity, vascularity, diffusion, cell density, infiltrations, perfusion, and metabolite changes) and 24 articles relevant to molecular biomarkers linked to imaging.

    RESULTS:: Genes found to correlate with various imaging phenotypes were EGFR, MGMT, IDH1, VEGF, PDGF, TP53, and Ki-67. EGFR is the most studied gene related to imaging characteristics in the studies reviewed (41.7%), followed by MGMT (20.8%) and IDH1 (16.7%). A summary of the relationship amongst glioma morphology, gene expressions, imaging characteristics, prognosis and therapeutic response are presented.

    CONCLUSION:: The use of radiogenomics can provide insights to understanding tumour biology and the underlying molecular pathways. Certain MRI characteristics that show strong correlations with EGFR, MGMT and IDH1 could be used as imaging biomarkers. Knowing the pathways involved in tumour progression and their associated imaging patterns may assist in diagnosis, prognosis and treatment management, while facilitating personalised medicine.

    ADVANCES IN KNOWLEDGE:: Radiogenomics can offer clinicians better insight into diagnosis, prognosis, and prediction of therapeutic responses of glioma.

    Matched MeSH terms: Biomarkers, Tumor/analysis
  16. Lee PY, Low TY, Jamal R
    Adv Clin Chem, 2018 12 27;88:67-89.
    PMID: 30612607 DOI: 10.1016/bs.acc.2018.10.004
    The life span of cancer patients can be prolonged with appropriate therapies if detected early. Mass screening for early detection of cancer, however, requires sensitive and specific biomarkers obtainable from body fluids such as blood or urine. To date, most biomarker discovery programs focus on the proteome rather than the endogenous peptidome. It has been long-established that tumor cells and stromal cells produce tumor resident proteases (TRPs) to remodel the surrounding tumor microenvironment in support of tumor progression. In fact, proteolytic products of TRPs have been shown to correlate with malignant behavior. Being of low molecular weight, these unique peptides can pass through the endothelial barrier of the vasculature into the bloodstream. As such, the cancer peptidome has increasingly become a focus for biomarker discovery. In this review, we discuss on the various aspects of the peptidome in cancer biomarker research.
    Matched MeSH terms: Biomarkers, Tumor/analysis
  17. McCart Reed AE, Kalaw E, Nones K, Bettington M, Lim M, Bennett J, et al.
    J Pathol, 2019 02;247(2):214-227.
    PMID: 30350370 DOI: 10.1002/path.5184
    Metaplastic breast carcinoma (MBC) is relatively rare but accounts for a significant proportion of global breast cancer mortality. This group is extremely heterogeneous and by definition exhibits metaplastic change to squamous and/or mesenchymal elements, including spindle, squamous, chondroid, osseous, and rhabdomyoid features. Clinically, patients are more likely to present with large primary tumours (higher stage), distant metastases, and overall, have shorter 5-year survival compared to invasive carcinomas of no special type. The current World Health Organisation (WHO) diagnostic classification for this cancer type is based purely on morphology - the biological basis and clinical relevance of its seven sub-categories are currently unclear. By establishing the Asia-Pacific MBC (AP-MBC) Consortium, we amassed a large series of MBCs (n = 347) and analysed the mutation profile of a subset, expression of 14 breast cancer biomarkers, and clinicopathological correlates, contextualising our findings within the WHO guidelines. The most significant indicators of poor prognosis were large tumour size (T3; p = 0.004), loss of cytokeratin expression (lack of staining with pan-cytokeratin AE1/3 antibody; p = 0.007), EGFR overexpression (p = 0.01), and for 'mixed' MBC, the presence of more than three distinct morphological entities (p = 0.007). Conversely, fewer morphological components and EGFR negativity were favourable indicators. Exome sequencing of 30 cases confirmed enrichment of TP53 and PTEN mutations, and intriguingly, concurrent mutations of TP53, PTEN, and PIK3CA. Mutations in neurofibromatosis-1 (NF1) were also overrepresented [16.7% MBCs compared to ∼5% of breast cancers overall; enrichment p = 0.028; mutation significance p = 0.006 (OncodriveFM)], consistent with published case reports implicating germline NF1 mutations in MBC risk. Taken together, we propose a practically minor but clinically significant modification to the guidelines: all WHO_1 mixed-type tumours should have the number of morphologies present recorded, as a mechanism for refining prognosis, and that EGFR and pan-cytokeratin expression are important prognostic markers. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
    Matched MeSH terms: Biomarkers, Tumor/analysis
  18. Siar CH, Ng KH
    Pathology, 2019 Aug;51(5):494-501.
    PMID: 31262562 DOI: 10.1016/j.pathol.2019.04.004
    The ameloblastoma is the most common and clinically significant odontogenic epithelial neoplasm known for its locally-invasive behaviour and high recurrence risk. Epithelial-to-mesenchymal transition (EMT) is a fundamental process whereby epithelial cells lose their epithelial characteristics and gain mesenchymal properties. EMT induction via transcription repression has been investigated in ameloblastoma. However, morphologically evident mesenchymal phenotypic transition remains ill-defined. To determine this, 24 unicystic (UA), 34 solid/multicystic (SA) and 18 recurrent ameloblastoma (RA) were immunohistochemically examined for three EMT-related mesenchymal markers, alpha smooth muscle actin (α-SMA), osteonectin and neuronal cadherin (N-cadherin). All three factors were heterogeneously detected in ameloblastoma samples (α-SMA, n=71/76, 93.4%; osteonectin, n=72/76, 94.7%; N-cadherin, n=24/76, 31.6%). In the tumoural parenchyma, immunoreactive cells were not morphologically distinct from their non-reactive cellular counterparts. Rather, α-SMA and osteonectin predominantly labelled the cytoplasm of central polyhedral > peripheral columnar/cuboidal tumour cells. N-cadherin demonstrated weak-to-moderate circumferential membranous staining in both neoplastic cell types and cytoplasmic expression in spindle-celled epithelium of desmoplastic amelobastoma. For all tumour subsets, α-SMA and osteonectin scored significantly higher in the stroma > parenchyma whilst α-SMA was overexpressed along the tumour invasive front > centre (p<0.05). Stromal N-cadherin scored higher in SA > UA and RA > UA (p<0.05). Other clinicopathological parameters showed no significant associations. Taken together, acquisition of mesenchymal traits without morphologically evident mesenchymal alteration suggests partial EMT in ameloblastoma. Stromal upregulation of these proteins in SA and RA implicates a role in local invasiveness.
    Matched MeSH terms: Biomarkers, Tumor/analysis
  19. Ramanathan S, Gopinath SCB, Md Arshad MK, Poopalan P
    Biosens Bioelectron, 2019 Sep 15;141:111434.
    PMID: 31238281 DOI: 10.1016/j.bios.2019.111434
    The pragmatic outcome of a lung cancer diagnosis is closely interrelated in reducing the number of fatal death caused by the world's top cancerous disease. Regardless of the advancement made in understanding lung tumor, and its multimodal treatment, in general the percentage of survival remain low. Late diagnosis of a cancerous cell in patients is the major hurdle for the above circumstances. In the new era of a lung cancer diagnosis with low cost, portable and non-invasive clinical sampling, nanotechnology is at its inflection point where current researches focus on the implementation of biosensor conjugated nanomaterials for the generation of the ideal sensing. The present review encloses the superiority of nanomaterials from zero to three-dimensional nanostructures in its discrete and nanocomposites nanotopography on sensing lung cancer biomarkers. Recent researches conducted on definitive nanomaterials and nanocomposites at multiple dimension with distinctive physiochemical property were focused to subside the cases associated with lung cancer through the development of novel biosensors. The hurdles encountered in the recent research and future preference with prognostic clinical lung cancer diagnosis using multidimensional nanomaterials and its composites are presented.
    Matched MeSH terms: Biomarkers, Tumor/analysis
  20. Samberkar S, Rajandram R, Mun KS, Samberkar P, Danaee M, Zulkafli IS
    Malays J Pathol, 2019 Dec;41(3):233-242.
    PMID: 31901907
    INTRODUCTION: Tissue biomarker carbonic anhydrase IX (CAIX) is purported to have prognostic value for renal cell carcinoma (RCC) but contradicting findings from previous studies have also been documented. This study aims to perform a systematic review and meta-analysis on the role of CAIX in RCC disease progression.

    MATERIALS AND METHODS: Following the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines, online searches of multiple databases were performed to retrieve articles from their inception until December 2017. Inclusion criteria included all English-based original articles of immunohistochemistry (IHC) studies investigating CAIX expression in human RCC tissue. Four articles were finally selected for meta-analysis with a total of 1964 patients. Standard meta-analysis methods were applied to evaluate the role of CAIX in RCC prognosis. The relative risk (RR) and its 95% confidence interval (CI) were recorded for the association between biomarker and prognosis, and data were analysed using MedCalc statistical software.

    RESULTS: The meta-analysis showed that high CAIX expression was associated with low tumour stage (RR 0.90%, 95% CI 0.849-0.969, p= 0.004), low tumour grade (RR 0.835%, 95% CI 0.732-0.983, p= 0.028), absence of nodal involvement (RR 0.814%, 95% CI 0.712-0.931, p= 0.003) and better ECOS-PS index (RR 0.888%, 95% CI 0.818-0.969, p= 0.007). The high tissue CAIX expression in RCC is hence an indication of an early malignancy with a potential to predict favourable disease progression and outcome.

    CONCLUSION: The measurement of this marker may be beneficial to determine the course of the illness. It is hoped that CAIX can be developed as a specific tissue biomarker for RCC in the near future.

    Matched MeSH terms: Biomarkers, Tumor/analysis*
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