I-Wei Chang

Chang Gung Memorial Hospital, T’ai-pei, Taipei, Taiwan

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Publications (5)13.11 Total impact

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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 · 2.84 Impact Factor
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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 · 1.92 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 · 0.64 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 · 3.12 Impact Factor
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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 · 4.59 Impact Factor