I-Wei Chang

E-Da Hospital, Kao-hsiung-shih, Kaohsiung, Taiwan

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Publications (13)35.15 Total impact

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    ABSTRACT: By data mining from published transcriptomic databases, we identified RAP2A as a significantly upregulated gene in nasopharyngeal carcinoma (NPC) tissues. RAP2A, a member of the RAS oncogene family, is involved in the process of GTP binding and GTPase activity. The aim of this study was to evaluate the expression of RAP2A and its prognostic impact in patients with early and locoregionally advanced NPC. RAP2A immunohistochemistry was performed for 124 NPC patients who were receiving standard treatment and had no initial distal metastasis. We also performed Western blotting to evaluate the endogenous protein expression of RAP2A in NPC cells and non-neoplastic mucosal cells. The result of RAP2A expression was further correlated with clinicopathological variables, disease-specific survival (DSS), distant metastasis-free survival (DMeFS), and local recurrence-free survival (LRFS). High expression of RAP2A was significantly associated with advanced primary tumor status (P = 0.024) and advanced TNM stage (P = 0.006). In univariate analysis, high expression of RAP2A served as a significant prognostic factor for inferior DSS (P < 0.0001), DMeFS (P < 0.0001), and LRFS (P < 0.0001). In multivariate analysis, RAP2A overexpression still independently predicted worse DSS (hazard ratio [HR] = 2.976, P < 0.001), DMeFS (HR = 4.233, P < 0.001), and LRFS (HR = 4.156, P < 0.001). Moreover, Both HONE1 and TW01 NPC cells, but not non-neoplastic DOK cells demonstrated significantly increased RAP2A expression. Overexpression of RAP2A is associated with advanced disease status and may therefore be an important prognosticator for poor outcomes in NPC, as well as a potential therapeutic target to aid in developing effective treatment modalities.
    American Journal of Translational Research 07/2015; 7(5):912-21. · 3.40 Impact Factor
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    ABSTRACT: Amino acid biosynthesis is one of the cardinal events of carcinogenesis that has not been investigated in urothelial carcinoma (UC). By data mining a published transcriptomic database of UCs of urinary bladder (UBUCs) (GSE31684), we identified branched-chain amino acid transaminase 1 (BCAT1) as the most significantly stepwise upregulated gene during tumor progression among those associated with amino acid biosynthetic process (GO:0008652). Accordingly, we analyzed BCAT1 transcript and protein expression with their clinicopathological significance. We used real time RT-PCR to detect BCAT1 transcript levels in 20 UCs of upper tract (UTUCs) and 20 UBUCs, respectively. Immunohistochemical study was performed to determine BCAT1 protein expression in 340 UTUCs and 295 UBUCs. Higher BCAT1 transcript levels were associated with higher pT status in both groups (p<0.05). BCAT1 protein overexpression was also significantly associated with adverse clinicopathological features, e.g., advanced pT stage, nodal metastasis, high pathological grade and etc. (p<0.05). BCAT1 overexpression predicted worse disease-specific survival and metastasis-free survival in both univariate and multivariate analyses (p≤0.001). BCAT1 overexpression is associated with advanced tumor status, and implies adverse clinical outcomes of UCs, suggesting its role in tumor progression and could serve as a prognostic biomarker and a novel therapeutic target in UC. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Histopathology 07/2015; DOI:10.1111/his.12778 · 3.45 Impact Factor
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    ABSTRACT: Skull and intracranial metastases from hepatocellular carcinoma (HCC) have seldom been reported. A skull metastasis of HCC with a tumor bleeding resulting in spontaneous subdural hematoma (SDH) is extremely unusual. We report the first case of acute spontaneous SDH in a 69-year-old woman who presented with acute onset of headache, because of tumor bleeding caused by skull metastasis of HCC. A 69-year-old woman was referred to our hospital because of progressive headache, nausea, and vomiting for 3 days. Brain computed tomography (CT) performed in the emergency department (ED) revealed a left temporal SDH with a slight mass effect and a small left temporal bone erosion. Tri-phasic abdominal CT demonstrated a large right lobe liver tumor compatible with HCC. She experienced progressive deterioration of consciousness in the intensive care unit. Follow-up CT showed an enlargement of the SDH. An emergency craniotomy for hematoma evacuation and removal of skull tumor was performed. She regained consciousness and had no neurological deficits during the postoperative course. Pathological examination of the skull specimen indicated metastasis of a HCC. Patients with acute SDH without a history of head injury are rarely encountered in the ED. Metastatic carcinoma with bleeding should be included as a differential diagnosis for acute spontaneous SDH. Before an operation for SDH, the possibility of metastatic lesion of the skull should be considered in the surgical planning and the origin of malignancy should be sought.
    BMC Surgery 05/2015; 15(1):60. DOI:10.1186/s12893-015-0045-x · 1.40 Impact Factor
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    ABSTRACT: Neoadjuvant concurrent chemoradiotherapy has been widely used for rectal cancer to improve local tumor control. The varied response of individual tumors encouraged us to search for useful biomarkers to predict the therapeutic response. The study was aimed to evaluate the prognostic impact of lipid biosynthesis-associated biomarkers in rectal cancer patients treated with preoperative chemoradiotherapy. Through analysis of the previously published gene expression profiling database focusing on genes associated with lipid biosynthesis, we found that HSD17B2 and HMGCS2 were the top two significantly upregulated genes in the non-responders. We further evaluated their expression by immunohistochemistry in the pre-treatment tumor specimens from 172 patients with rectal cancer and statistically analyzed the associations between their expression and various clinicopathological factors, as well as survival. High expression of HMGCS2 or HSD17B2 was significantly associated with advanced pre- and post-treatment tumor or nodal status (P < 0.001) and lower tumor regression grade (P < 0.001). More importantly, high expression of either HMGCS2 or HSD17B2 was of prognostic significance, with HMGCS2 overexpression indicating poor prognosis for disease-free survival (P = 0.0003), local recurrence-free survival (P = 0.0115), and metastasis-free survival (P = 0.0119), while HSD17B2 overexpression was associated with poor prognosis for disease-free survival (P <0.0001), local recurrence-free survival (P = 0.0009), and metastasis-free survival (P < 0.0001). In multivariate analysis, only HSD17B2 overexpression remained as an independent prognosticator for shorter disease-free survival (P < 0.001) and metastasis-free survival (P = 0.008). In conclusion, high expression of either HSD17B2 or HMGCS2 predicted poor susceptibility of rectal cancer to preoperative chemoradiotherapy. Both acted as promising prognostic factors, particularly HSD17B2.
    Tumor Biology 05/2015; DOI:10.1007/s13277-015-3503-2 · 3.61 Impact Factor
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    ABSTRACT: Oxidative stress is believed to be one of the important etiologies in carcinogenesis that has not been systemically investigated in urothelial carcinoma (UC). Through data mining from a published transcriptomic database of UC of urinary bladders (UBUCs) (GSE31684), glutathione peroxidase 2 (GPX2) was identified as the most significant downregulated gene among those response to oxidative stress (GO:0006979). We therefore analyze GPX2 transcript and protein expressions and its clinicopathological significance. Real-time RT-PCR assay was used to detect GPX2 mRNA level in 20 fresh UBUC specimens. Immunohistochemistry was used to determine GPX2 protein expression in 340 urothelial carcinomas of upper tracts (UTUCs) and 295 UBUCs with mean/median follow-up of 44.7/38.9 and 30.8/23.1 months, respectively. Its expression status was further correlated with clinicopathological features and evaluated for its impact on disease-specific survival and metastasis-free survival (MeFS). Decrease in GPX2 transcript level was associated with both higher pT and positive nodal status in 20 UBUCs (all p < 0.05). GPX2 protein underexpression was also significantly associated with advanced pT status, nodal metastasis, high histological grade, vascular invasion, and frequent mitoses in both groups of UCs (all p < 0.05). GPX2 underexpression not only predicted dismal DDS and MeFS at univariate analysis, but also implicated worse DDS (UTUC, p = 0.002; UBUC, p = 0.029) and MeFS (UTUC, p = 0.001; UBUC, p = 0.032) in multivariate analysis. GPX2 underexpression is associated with advanced tumor status and implicated unfavorable clinical outcome of UCs, suggesting its role in tumor progression and may serve as a theranostic biomarker of UCs.
    World Journal of Urology 03/2015; 7(4). DOI:10.1007/s00345-015-1522-7 · 2.67 Impact Factor
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    ABSTRACT: Genes associated with protein folding have been found to have certain prognostic significance in a subset of cancers. The aim of this study is to evaluate the clinical impact of DNAJC12 expression in patients with rectal cancers receiving neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery. Through data mining from a public transcriptomic dataset of rectal cancer focusing on genes associated with protein folding, we found DNAJC12, a member of the HSP40/DNAJ family, was the most significant such gene correlated with the CCRT response. We further evaluated the expression of DNAJC12 by immunohistochemistry in the pre-treatment tumor specimens from 172 patients with rectal cancers. From this set, we statistically analyzed the association of DNAJC12 expression with various clinicopathological factors, tumor regression grade, overall survival (OS), disease-free survival (DFS) and local recurrence-free survival (LRFS). High expression of DNAJC12 was significantly associated with advanced pre- and post-treatment tumor status (P<0.001), advanced pre- and post-treatment nodal status (P<0.001), increased vascular invasion (P=0.015), increased perineural invasion (P=0.023) and lower tumor regression grade (P=0.009). More importantly, high expression of DNAJC12 was found to be correlated with poor prognosis for OS (P=0.0012), DFS (P<0.0001) and LRFS (P=0.0001). In multivariate analysis, DNAJC12 overexpression still emerged as an independent prognosticator for shorter OS (P=0.040), DFS (P<0.001) and LRFS (P=0.016). The data indicate that DNAJC12 overexpression acts as a negative predictive factor for the response to neoadjuvant CCRT and was significantly associated with shorter survival in patients with rectal cancers receiving neoadjuvant CCRT followed by surgery. Copyright © 2015. Published by Elsevier Inc.
    Experimental and Molecular Pathology 03/2015; 98(3). DOI:10.1016/j.yexmp.2015.03.029 · 2.71 Impact Factor
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    ABSTRACT: Medulloblastoma, a malignant, invasive embryonal tumor of the cerebellum, occurs most often in children. It has high metastatic potential and is usually treated by aggressive multimodal therapy, including surgery, chemotherapy and craniospinal irradiation. Multiple secondary tumors have been reported following craniospinal irradiation. It is rare with the occurrence of oligodendroglioma after irradiation. In this report, we described a patient with secondary oligodendroglioma after postoperative craniospinal irradiation for medulloblastoma.
    International journal of clinical and experimental pathology 05/2014; 7(4):1796-9. · 1.89 Impact Factor
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    ABSTRACT: Despite recent improvements in the diagnosis and treatment, the final outcomes in patients with nasopharyngeal carcinomas (NPC) still remain suboptimal. Through data mining from published transcriptomic database with further bioinformatic validation, fibronectin (FN1) was identified as a differentially upregulated gene in NPC tissues, which implicates the transition from epithelial to mesenchymal phenotype (EMT) and promotes metastasis. Given the roles of fibronectin in risk stratification and in the frontline therapeutics of common carcinomas, such as renal cell cancer, we explored fibronectin immunoexpression status and its associations with clinicopathological variables and survival in a well-defined cohort of NPC patients. Fibronectin immunohistochemistry was retrospectively performed and analyzed using H-score for 124 biopsy specimens from NPC patients who received standard treatment without distant metastasis at initial diagnosis. Those cases with H-score higher than the median value were regarded as fibronectin overexpression. The findings were correlated with clinicopathological variables, EBV latent membrane protein 1 (LMP1) expression, disease-specific survival (DSS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS). Fibronectin overexpression was significantly associated with American Joint Committee on Cancer (AJCC) stages III-IV (p = 0.019) and LMP1 expression (p = 0.004), and univariately predictive of adverse outcomes for DSS, DMFS, and LRFS (all p < 0.0001). In the multivariate comparison, fibronectin overexpression still remained prognostically independent to portend worse DSS (p < 0.01, hazard ratio = 5.958), DMFS (p < 0.01, hazard ratio = 5.728), and LRFS (p < 0.01, hazard ratio = 5.411) together with advanced AJCC stages III-IV. Fibronectin is upregulated in a subset of NPCs, and its increased immunoexpression significantly correlated with advanced features, justifying the potentiality of fibronectin as a theragnostic biomaker of NPC.
    Tumor Biology 10/2013; 35(2). DOI:10.1007/s13277-013-1235-8 · 3.61 Impact Factor
  • Pathology International 01/2013; 63(1):73-6. DOI:10.1111/pin.12026 · 1.69 Impact Factor
  • I-Wei Chang · Han-Ku Chen · Ming-Chun Ma · Wan-Ting Huang
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    ABSTRACT: Anaplastic large cell lymphoma (ALCL) is a type of T-cell lymphoma with a relatively favorable prognosis. However, a certain group of ALCLs is highly aggressive, featuring paraneoplastic leukocytosis (PL) in clinical presentation. The present study evaluated five cases of ALCL presenting with PL, including four men and one woman, with a median age of 58 years. All cases revealed leukocytosis with a range from 15.3 to 112.9 × 10(3) /μL. Five (100%) and 4 (80%) cases demonstrated immunoreactivity for granulocyte-colony-stimulating factor (G-CSF) and tumor necrosis factor-alpha (TNF-α), respectively. There were significant differences in the expression of G-CSF and TNF-α between ALCL cases with or without PL (p < 0.05 for both). The prognosis of ALCL patients with PL was poor. Four of five patients (80%) died of the disease within a median survival time of 3.5 weeks. The release of G-CSF and TNF-α from lymphoma cells may associate with ALCL presenting with PL, leading to cytokine crisis and even poorer prognosis.
    Apmis 11/2011; 119(11):794-801. DOI:10.1111/j.1600-0463.2011.02811.x · 2.04 Impact Factor
  • Jui-Wei Lin · You-Ting Wu · I-Wei Chang
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    ABSTRACT: Gliosarcoma is an uncommon variant of glioblastoma characterized by a biphasic tissue pattern of glial and mesenchymal differentiation. O6-methylguanine DNA methyltransferase (MGMT) is a DNA repair protein that removes mutagenic and cytotoxic adducts from O6-guanine in DNA. Lack of MGMT protein expression immunohistochemically is related to drug responses in patients of malignant glioma treated with alkylating agents. Epidermal growth factor receptor (EGFR) is the most frequently amplified gene in glioblastoma and associated with tumor invasiveness, angiogenesis, poor survival, and resistance to radiation therapy. To elucidate the relationship between the statuses of the MGMT as well as EGFR proteins and the prognosis. The study was undertaken on samples received at the Department of Pathology from 2003 to 2009. Clinicopathologic and immunohistochemical study of seven cases was performed. This series included three men and four women with a mean age of 49.3 years at first surgery. The median progression-free survival (PFS) was 22.2 months and 8.6 months for primary tumors with 0 to 1+ and 2+ to 3+ MGMT staining, respectively; the median overall survival (OS) was 27.5 months and 14.2 months for primary tumors with 0 to 1+ and 2+ to 3+ MGMT staining, respectively. The median PFS was 17.2 months and 11.2 months for primary tumors with 0 to 1+ and 2+ to 3+ EGFR staining, respectively; the median OS was 20.4 months and 17.7 months for primary tumors with 0 to 1+ and 2+ to 3+ EGFR staining, respectively. The series showed that MGMT and EGFR protein expressions were both unfavorable prognostic factors for patients with gliosarcoma.
    Indian Journal of Pathology and Microbiology 10/2011; 54(4):683-7. DOI:10.4103/0377-4929.91491 · 0.47 Impact Factor
  • I-Wei Chang · Jui-Wei Lin · You-Ting Wu
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    ABSTRACT: Meningeal hemangiopericytoma (HPC) is a clinicopathologically well-characterized malignancy with a high tendency to recur locally and to metastasize outside the central nervous system (CNS). We render clinicopathologic features of 12 cases of this uncommon tumor to further elucidate the relationship between the status of the DNA-repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) and the prognosis. Twenty-five specimens of meningeal HPC belonging to 12 patients were obtained at a single institution from 1992 to 2001. Correlations of histologic parameters, immunohistochemical study and clinical features were assessed. This series included five men and seven women with a median age of 37.5 years at the first surgery. The median post-operative follow-up period was 7.6 years. Six patients (55%) had single or multiple local tumor recurrences. The mean time to recurrence was 6.7 years. Distant metastasis occurred in three patients (27%) at a mean time of 6.5 years after first operation. The most frequent metastatic sites were liver and lung. Histopathologically, eight primary tumors (67%) belonged to WHO grade II, while four primary tumors (33%) belonged to WHO grade III. Immunohistochemically, 18% primary tumors exhibited 3+ to 4+ nuclear staining for MGMT protein, 18% exhibited 2+ staining, and 64% exhibited 0 to 1+ staining. The overall survival rate was 67 and 33% for primary tumors with 0 to 1+ and 2+ to 4+ MGMT staining, respectively (P = 0.018). The study illustrates aggressive behavior of meningeal HPC and the prognostic value of the status of MGMT protein expression.
    Journal of Neuro-Oncology 06/2011; 105(3):563-72. DOI:10.1007/s11060-011-0620-7 · 3.07 Impact Factor
  • I-Wei Chang · Hsuan-Ying Huang · Ming-Tse Sung
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    ABSTRACT: Melanotic Xp11 translocation renal cancer is a recently recognized aggressive epithelioid neoplasm with features overlapping between PEComa, carcinoma, and melanoma. We describe morphologic and immunohistochemical characteristics of a melanotic Xp11 translocation renal cancer occurring in an 18-year-old girl and perform molecular genetic studies to analyze its genetic alterations and related melanogenetic activities. The tumor was composed of solid nests of epithelioid cells bearing abundant clear to finely granular eosinophilic cytoplasm and separated by delicate vascular septa. Finely granular and nonrefractile brown melanin pigments, highlighted by Fontana-Masson stain, were scattered through the tumor. By immunohistochemistry, the tumor was diffusely and strongly labeled by TFE3 and focally stained by HMB45 in a patchy pattern. In contrast, all other applied immunomarkers, including cytokeratins, epithelial membrane antigen, vimentin, CD10, S-100, smooth muscle actin, desmin, c-kit, CD68, and microphthalmia-associated transcription factor, were nonreactive to the tumor. Reverse transcription-polymerase chain reaction and validating sequencing demonstrated PSF-TFE3 gene fusion, a novel exon composition juxtaposing PSF exon 9 to TFE3 exon 5. Up-regulations of melanogenesis-associated regulators, including microphthalmia-associated transcription factor, tyrosinase (TYR), and tyrosinase-related protein 1 (TYRP1), were identified in the tumor by semiquantitative reverse transcription-polymerase chain reaction. The morphologic and immunohistochemical discrepancies between this intriguing melanotic tumor and other documented renal cell carcinomas bearing identical PSF-TFE3 gene fusion may suggest melanotic Xp11 translocation renal cancer is a distinct entity among the MiT/TFE family neoplasms.
    The American journal of surgical pathology 10/2009; 33(12):1894-901. DOI:10.1097/PAS.0b013e3181ba7a5f · 5.15 Impact Factor