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Puay-Hoon Tan

Publications and source records attributed to Puay-Hoon Tan.

At least 19 recordsLinked to original sources
PubMed2006

Divergent pathway of intestinal metaplasia and cystitis glandularis of the urinary bladder.

Intestinal metaplasia has been proposed to be a precursor lesion of adenocarcinoma in the urinary bladder. CDX2 is a transcription factor that is encoded by a homeotype gene that plays an essential role in the differentiation and proliferation of intestinal epithelial cells. Hepatocyte-specific antigen (Hep) has also been shown to be a useful marker of intestinal metaplasia. Tissues from 46 patients, including 22 cases of intestinal metaplasia of the urinary bladder, 11 cases of typical cystitis glandularis, and 13 cases containing both lesions, were selected and immunohistochemical stains for CDX2, Hep, cytokeratin 20 (CK20), and cytokeratin 7 (CK7) were performed. Nuclear staining for CDX2 was observed in 29 of 35 (83%) cases of intestinal metaplasia of the urinary bladder. In contrast, nuclear staining for CDX2 was not observed in any case of typical cystitis glandularis; however, seven of 24 (29%) cases showed aberrant cytoplasmic expression in a mean of 37% of cells. CK20 was expressed in 28 of 35 (80%) cases of intestinal metaplasia, but was observed in only one of 24 (4%) cases of cystitis glandularis in 15% of cells. CK7 was expressed in only six of 35 (17%) cases of intestinal metaplasia, whereas expression of CK7 was observed in all cases (100%) of typical cystitis glandularis with a mean percentage of positively staining cells of 63%. The mean percentages of positively staining cells in intestinal metaplasia with CDX2, CK20, and CK7 were 55, 49, and 53%, respectively. All examples of both intestinal metaplasia and typical cystitis glandularis were uniformly negative for Hep. In the urinary bladder, intestinal metaplasia and typical cystitis glandularis have sharply contrasting immunoprofiles. Additionally, the absence of Hep staining in intestinal metaplasia of the urinary bladder, despite its morphologic resemblance to normal colonic mucosa and intestinal metaplasia in other organs, may signify the presence of unique metaplastic pathways in the urinary bladder.

Autoantigens↗
PubMed2006

Inverted papilloma of the urinary bladder: a molecular genetic appraisal.

Inverted papilloma of urinary bladder is an uncommon urothelial neoplasm. Its relationship to urothelial carcinoma is controversial. Little is known of the genetic abnormalities of inverted papilloma. To better understand its genetics, we analyzed 39 inverted papillomas, including 36 from men and three from women, for loss of heterozygosity (LOH). We examined four polymorphic microsatellite markers located on chromosome 9q32-33(D9S177), chromosome 9p22 (IFNA), chromosome 3p14.2 (D3S1300) and chromosome 17p13.1 (TP53), where genetic alterations occur frequently in urothelial carcinomas. Additionally, the status of inactivation of X-chromosome was examined in three female patients. The frequency of LOH in informative cases was 8% (3 of 37) for D9S177, 10% (4 of 38) for TP53, 8% (3 of 37) for IFNA and 8% (3 of 36) for D3S1300. In the analysis of X-chromosome inactivation, all three cases yielded informative results and one had nonrandom inactivation of X-chromosomes. The monoclonal origin demonstrated in the study of X-chromosome inactivation indicates the clonal process of inverted papilloma; however, the low incidence of LOH supports the view that inverted papilloma in urinary bladder is a benign neoplasm with molecular genetic abnormalities different from those of urothelial carcinoma.

Female↗
PubMed2006

Immunohistochemical expression of heparan sulfate correlates with stromal cell proliferation in breast phyllodes tumors.

Phyllodes tumors are fibroepithelial neoplasms typified by stromal proliferation. We have previously shown the role of pathologic parameters and the prognostic significance of p53 and CD117 protein expression in these tumors. In this study, we evaluated the expression of heparan sulfate, which has been implicated in many biological processes such as cell adhesion, embryogenesis, and tumorigenesis (including malignant transformation of mammary cells) in 232 breast phyllodes tumors. We used a monoclonal antibody, 10E4, to examine the localization of heparan sulfate in phyllodes tumors by immunohistochemistry. The immunoreactivity of both epithelial and stromal components was examined and analyzed with pathological parameters and other immunohistochemical markers, including p53, MIB1, bcl2, and CD117. Stromal 10E4 expression was significantly associated with tumor grade, stromal p53, and MIB1 expression in proliferating cells, suggesting that heparan sulfate may participate in malignant tumor growth.

Antibodies, Antinuclear↗
PubMed2006

p63 is useful in the diagnosis of mammary metaplastic carcinomas.

AIMS: p63 has been recently reported to be expressed in sarcomatoid/metaplastic carcinoma of the breast, in addition to its role as a myoepithelial marker. A large series of 34 metaplastic carcinomas, including cases with pure epithelial component (squamous cell and adenosquamous carcinomas), biphasic tumours with carcinomatous and sarcomatoid components and monophasic tumours with only spindle cell component, were evaluated for p63 expression with respect to the different cellular components. METHODS: All of the metaplastic carcinomas were assessed for p63 and conventional epithelial and mesenchymal markers of AE1/3, CAM5.2 and vimentin by immunohistochemistry. RESULTS: All of the different categories of metaplastic carcinomas showed similar clinico-pathological features (patient age, tumour size, nuclear grade, mitotic activity, lymph node status and hormonal receptor status). For metaplastic carcinoma with epithelial component only, p63 was only expressed in the squamous cell component, but not the adenocarcinoma component. Eight of the 10 tumours were positive for p63. For the tumours with sarcomatoid component, either singly or together with carcinomatous component, p63 was positive in 14 of 24 cases. Pure sarcomas and carcinomas were all negative for p63 staining by immunohistochemistry, thus rendering p63 staining highly specific for diagnosing metaplastic carcinoma. CONCLUSIONS: Using p63 for diagnosis of metaplastic carcinoma gives a sensitivity of 65%, a specificity of 96%, a positive predictive value of 96%, and a negative predictive value of 66% and an accuracy of 78%. p63 may be used as an adjunct marker in the diagnosis of metaplastic carcinoma.

Adult↗
PubMed2006

Supervised learning-based cell image segmentation for p53 immunohistochemistry.

In this paper, we present two new algorithms for cell image segmentation. First, we demonstrate that pixel classification-based color image segmentation in color space is equivalent to performing segmentation on grayscale image through thresholding. Based on this result, we develop a supervised learning-based two-step procedure for color cell image segmentation, where color image is first mapped to grayscale via a transform learned through supervised learning, thresholding is then performed on the grayscale image to segment objects out of background. Experimental results show that the supervised learning-based two-step procedure achieved a boundary disagreement (mean absolute distance) of 0.85 while the disagreement produced by the pixel classification-based color image segmentation method is 3.59. Second, we develop a new marker detection algorithm for watershed-based separation of overlapping or touching cells. The merit of the new algorithm is that it employs both photometric and shape information and combines the two naturally in the framework of pattern classification to provide more reliable markers. Extensive experiments show that the new marker detection algorithm achieved 0.4% and 0.2% over-segmentation and under-segmentation, respectively, while reconstruction-based method produced 4.4% and 1.1% over-segmentation and under-segmentation, respectively.

Algorithms↗
PubMed2006

Metallothionein as a prognostic biomarker in breast cancer.

Breast cancer is the most common cancer in women, with a general upward trend in incidence. Basic and clinical breast cancer research has continued at a rapid pace, in the endeavor to understand the biology of the disease so as to improve management of patients. Besides traditional pathological indicators, expression of molecular markers in breast cancer has also been comprehensively investigated. This paper will focus on the prognostic utility of metallothioneins (MTs), a family of low molecular weight metal binding proteins encoded by at least 10 functional MT genes that are associated with cell proliferation in breast cancer. Evidence that MT is a potential prognostic biomarker for breast cancer is supported by many reports in the literature. Expression of the MT protein has been detected by immunohistochemistry in a significant portion of invasive ductal breast cancers. MT expression has also been well studied in association with traditional clinico-pathological parameters of breast cancers. Generally, higher MT expression in breast cancers is predictive of worse patient outcomes. The relationship of MT isoforms to histological grade, estrogen receptor (ER) status, and prognosis will also be discussed.

Biomarkers, Tumor↗
PubMed2005

Mucinous nonneoplastic cyst of the pancreas: a truly novel pathological entity?

Recently, a novel and distinct pancreatic cystic tumor termed "mucinous nonneoplastic" cyst was described in the literature. We report our experience with a 71-year-old female with a cystic tumor in the body of the pancreas demonstrating features suggestive of this diagnosis. We also review the literature regarding this "novel" pathological entity and discuss critically its existence and its differential diagnoses.

Aged↗
PubMed2005

Immunohistochemical detection of Ki67 in breast cancer correlates with transcriptional regulation of genes related to apoptosis and cell death.

Ki67 is a nuclear protein that is tightly linked to the cell cycle. It is a marker of cell proliferation and has been used to stratify good and poor prognostic categories in invasive breast cancer. Its correlation with gene expression patterns has not been fully elucidated. In this study, Ki67 immunohistochemistry using the MIB-1 antibody was performed on sections cut from 21 formalin-fixed, paraffin-embedded invasive breast cancers. Scoring was determined as nil (no immunostaining), low (10% or less immunopositivity) or high (>10% immunoreactive cells) respectively. The relationship of Ki67 immunohistochemical detection with clinicopathologic parameters was evaluated. Using Affymetrix U133A GeneChips, expression profiles for these tumors were generated and correlated with Ki67 immunohistochemical findings. Analysis of variance was used to define genes that were differentially regulated between the groups. Real-time polymerase chain reaction (PCR) was used to confirm the presence of a downregulated gene. Our results showed high, low and nil Ki67 immunostaining in nine (43%), six (28.5%) and six (28.5%) invasive breast cancers respectively, with increased Ki67 protein expression correlating with high histologic grade (P=0.02), mitotic score (P=0.001) and estrogen receptor immunonegativity (P=0.002). Expression profiling trends of the Ki67 gene mirrored the observed proportions of immunostained cells when the Ki67 immunoscore was >10%. Genes related to apoptosis and cell death (bcl2, MAP2K4, TNF10) were noted to be downregulated in tumors that disclosed >40% Ki67 immunostaining (P<0.001). Downregulation of the bcl2 gene was confirmed at the RNA level by real-time RT-PCR. Differential regulation of these genes, especially bcl2, may contribute to the biological nature of clinically more aggressive and highly proliferative breast cancers.

Adult↗
PubMed2005

p53 and c-kit (CD117) protein expression as prognostic indicators in breast phyllodes tumors: a tissue microarray study.

Breast phyllodes tumors are fibroepithelial neoplasms whose clinical behavior is difficult to predict on histology. There is relatively scant data on the role of biological markers. In this study, we determined if p53 and CD117 (c-kit) protein expression was predictive of behavior in a series of 335 phyllodes tumors diagnosed at the Singapore General Hospital, using immunohistochemistry on tissue microarrays. Representative areas from 250 (75%) benign, 54 (16%) borderline and 31 (9%) malignant phyllodes tumors were selected for construction of tissue microarrays using the 2 mm punch. Immunohistochemistry for p53 and CD117 was carried out using the streptavidin-biotin method. Staining proportion and intensity of both epithelial and stromal elements were analyzed. p53 immunostaining was observed in the epithelium of 28 (10%) of 278 microarrays; myoepithelium of 53 (21%) of 251 microarrays; and stromal cells in 105 (36%) of 289 microarrays. CD117 immunohistochemical reactivity was noted in epithelial and stromal components of 175 (of 267, 66%) and 17 (of 273, 6%) microarrays, respectively. Stromal p53 and CD117 protein expression was associated with tumor grade (P < 0.05). Of 43 (13%) women who suffered recurrences during the follow-up period, CD117 stromal staining predicted recurrent disease (P<0.05), but p53 was not correlative. We conclude that tissue microarrays are a convenient method for evaluating immunostaining results of large numbers of phyllodes tumors. Although positive p53 stromal immunohistochemical detection may corroborate histologic malignancy, it is CD117 protein expression in phyllodes tumor stromal cells that may be of potential utility in predicting recurrent disease.

Adolescent↗
PubMed2005

Phyllodes tumors of the breast: the role of pathologic parameters.

We aimed to establish whether morphologic parameters were prognostically important in a large series of breast phyllodes tumors in Asian women. Of 335 phyllodes tumors diagnosed at the Department of Pathology, Singapore General Hospital, Singapore, between January 1992 and December 2002, 250 (74.6%) were benign, 54 (16.1%) borderline, and 31 (9.3%) malignant, based on histologic review of archival slides. Of the women, 43 (12.8%) experienced recurrences during the follow-up period. Recurrent disease was correlated with grade or classification (P = .028), stromal atypia (P = .016), stromal hypercellularity (P = .046), and permeative microscopic borders (P = .021). Multivariate analysis revealed that independent predictors of recurrence were pseudoangiomatous stromal hyperplasia (PASH) and margin status, whereby the presence of PASH and complete or negative margins reduced recurrence hazards by 51.3% and 51.7% respectively. The 7 women who died of disease during follow-up had malignant phyllodes tumor at the outset and experienced recurrences, and death was preceded by distant metastases.

Adolescent↗
PubMed2005

Y-box binding protein, YB-1, as a marker of tumor aggressiveness and response to adjuvant chemotherapy in breast cancer.

The Y-box binding protein 1 (YB-1) regulates gene expression through transcription and translation. YB-1 has been shown to be associated with up-regulation of P-glycoprotein (Pgp), an ATP-binding transporter involved in multi-drug resistance. In this study, we determined the prognostic significance of YB-1 and its relationship with Pgp in patients with breast cancer. YB-1 and Pgp expression were evaluated by immunohistochemistry in resected specimens of infiltrative ductal breast cancers from 99 patients and 57 patients respectively and correlated with clinicopathological parameters and adjuvant chemotherapy regimes. The antibody for the YB-1 protein was prepared by injecting a rabbit with a purified recombinant chicken YB1 protein. The relationship between YB-1 and Pgp was also evaluated by a computational approach using the Resonant Recognition Model (RRM). We found that breast tumors which were both estrogen receptor-negative and lymph node positive were associated with high YB-1 expression (P=0.017). In patients who did not receive adjuvant chemotherapy, recurrence risk was reduced in breast cancers having lower YB-1 expression (P=0.034), suggesting that high levels of YB-1 expression in breast cancer is associated with tumor aggressiveness. We were able to demonstrate a direct interaction between YB-1 and Pgp using the computer-based RRM. Interestingly, we found that patients who were on a chemotherapy regime which contained an anthracycline (a Pgp substrate) and subsequently developed recurrence, had a higher YB-1 score compared to patients on the Cyclophosphamide/Methotrexate/5-Fluorouracil regime (P=0.024). YB-1 expression in breast cancer may be a potential marker of chemoresistance and could possibly aid in selection of the appropriate adjuvant chemotherapy regime for breast cancers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Expression of Y-Box binding protein-1 following hypericin-mediated photodynamic therapy in well-differentiated nasopharyngeal cancer in vivo.

The Y-Box binding protein, YB-1, belongs to a group in the DNA and RNA binding protein family. YB-1 is known to be expressed in a number of different cancers and reported to protect cells against DNA-damaging agents such as ultraviolet light. The purpose of this study was to determine if YB-1 levels are altered in photodynamic therapy (PDT)-treated nasopharyngeal cancer (NPC) cells. In this report, we show for the first time that YB-1 is expressed at both the mRNA and protein levels in well-differentiated NPC in vivo. YB-1 mRNA expression in tumor tissues from a murine well-differentiated HK1/NPC model showed no significant difference in mRNA levels following hypericin-PDT. Localization of the YB-1 protein by immuno-histochemistry revealed the presence of cytoplasmic YB-1 in the more mature and better differentiated cells of the untreated group, as well as cells that survived PDT treatment. Expression of the YB-1 protein may possibly influence the cellular stress response to hypericin-PDT and protect the cells from phototoxicity.

Animals↗
PubMed2004

Clinicopathological significance of metallothioneins in breast cancer.

Metallothioneins (MTs) are a family of metal binding proteins that play an important role in maintaining transition metal ion homoeostasis, redox balance in the cell and fundamental cellular processes such as proliferation and apoptosis. In humans, there are 4 groups of MT proteins which are encoded by 10 functional MT isoforms. In breast tissues, MT is primarily expressed in myoepithelial and malignant epithelial cells. Immunohistochemical studies have revealed that 26% to 100% of invasive ductal breast cancers express the MT protein. The MT-1F and MT-2A isoforms have been reported to be associated with higher histological grade in breast cancer, whereas higher MT-1E mRNA expression was found in estrogen receptor-negative tumors compared to their estrogen receptor-positive counterparts. A number of studies have shown that MT expression in breast cancer is associated with poorer prognosis. In addition, metallothionein expression may have a potential role in protecting the breast cancer cell from chemotherapeutic threats to survival.

Animals↗
PubMed2004

Phased-array magnetic resonance imaging of the prostate with correlation to radical prostatectomy specimens: local experience.

PURPOSE: To evaluate local experience of phased-array magnetic resonance imaging (MRI) in the staging of locally advanced prostate carcinoma with comparison to clinical staging. METHODS: The study population was 21 patients who underwent preoperative MRI with pelvic phased-array coils followed by radical prostatectomy. The MRI findings were correlated with completely embedded serially sliced and whole-mounted sections of the prostate gland and clinical staging. RESULTS: Overall accuracy of 57.1% was obtained, with specificity of 90.0% and sensitivity of 27.3%. All but one case of locally advanced disease missed by MRI was microscopic. Clinical staging in these cases also achieved accuracy of 57.1%, specificity of 90.0% and sensitivity of 27.3%. CONCLUSIONS: MRI with a phased-array coil has high specificity but low sensitivity for detection of extraprostatic disease. Phased-array MRI does not image microscopic tumour extension. It did not perform better than clinical staging and is not recommended for routine staging.

Aged↗
PubMed2003

Detection of HER2/neu gene amplification in archival paraffin-embedded breast cancer tissues by fluorescence in situ hybridization.

We evaluated HER2/neu gene amplification by fluorescence in situ hybridization (FISH) in archival paraffin-embedded breast cancer tissues. Tumors from 63 human invasive breast cancers were categorized into two groups depending on whether the paraffin-embedded tissue blocks had been stored for more or less than 12 months duration. These were subjected to routine and modified FISH protocols. As microwave oven formalin fixation of tissues was carried out in the majority of the older archived specimens, the effect of this fixation method was also analyzed. FISH signals were obtained in all 13 archival specimens stored for less than 12 months. However, in 50 specimens stored for more than 12 months duration, the procedure was successful in only 10 specimens (20%), for which the pretreatment procedure had to be individually optimized for each specimen. There was no significant difference in the detection of FISH signals between microwave oven and routinely fixed specimens.

Breast Neoplasms↗