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Chung-Che Chang

Publications and source records attributed to Chung-Che Chang.

At least 37 records · Page 2Linked to original sources
PubMed2003

Improved immunohistochemical evaluation of micrometastases in sentinel lymph nodes of cutaneous melanoma with 'MCW melanoma cocktail'--a mixture of monoclonal antibodies to MART-1, Melan-A, and tyrosinase.

BACKGROUND: MART-1, Melan-A, and Tyrosinase have shown encouraging results for evaluation of melanoma micrometastases in sentinel lymph nodes, as compared to conventionally used S-100 protein and HMB-45. To achieve higher sensitivity, some studies recommend evaluation of three sections, each at intervals of 200 micron. This would mean, routine staining of three adjacent sections in each of the three clusters at intervals of 200 micron, requiring nine slides resulting in added expense. If a cocktail of these antibodies could be used, only one section would be required instead of three generating significant cost savings. METHODS: We prepared a combination of monoclonal antibodies to these three immunomarkers in optimized dilutions (MART-1, clone M2-7C10, dilution 1:500; Melan-A, clone A103, dilution 1:100; and Tyrosinase, clone T311, dilution 1:50) and designated it as 'MCW melanoma cocktail'. Formalin-fixed paraffin-embedded tissue sections of sentinel lymph nodes from patients with cutaneous melanoma, without macro-metastases were evaluated with this cocktail. RESULTS: Melanoma micrometastases were easily detectable with the cocktail in 41 out of 188 slices (8/24 cases). The diagnostic accuracy amongst five pathologists did not show statistically significant difference. Out of 188 slices, 78 had adjacent sections immunostained individually with MART-1 and Melan-A during our previous study. Of these 78 slices, 21 were positive for melanoma micrometastases with MART-1 and Melan-A individually. However, the adjacent section of these slices immunostained with the cocktail detected metastases in four additional slices. Thus, MART-1 and Melan-A could not detect melanoma micrometastases individually in 16% (4/25) of slices positive with the cocktail. Benign capsular nevi were immunoreactive for the cocktail in 4.8% (9/188) slices. All 81 slices of negative test controls (sentinel lymph nodes of mammary carcinoma) were interpreted correctly as negative for melanoma micrometastases. CONCLUSIONS: The melanoma cocktail facilitated easy interpretation of melanoma micrometastases in sentinel lymph nodes with high interobserver agreement. There was improvement in detection rate with the cocktail as compared to MART-1 and Melan-A individually. Furthermore, this approach facilitates cost savings.

Antibodies, Monoclonal↗
PubMed2003

Colon biopsies for evaluation of acute graft-versus-host disease (A-GVHD) in allogeneic bone marrow transplant patients.

BACKGROUND: Proper histomorphological interpretation of intestinal acute graft versus host disease (A-GVHD) associated with allogeneic bone marrow transplantation (BMT) is critical for clinical management. However, studies methodically evaluating different histomorphological features of A-GVHD are rare. METHODS: Colonic biopsies from 44 allogeneic BMT patients having biopsy-proven cutaneous A-GVHD were compared with colon biopsies from 48 negative controls. RESULTS: A-GVHD showed intra-cryptal apoptosis in 91% and pericryptal apoptosis in adjacent lamina propria in 70% (p < 0.002). Nonspecific apoptosis along the surface epithelium was observed in all groups with comparable frequency. The number of apoptotic cells in mucosa were approximately four times (5.3 per 10 HPF) the negative controls (p < 0.002) in A-GVHD group. 48% of cases with A-GVHD showed decreased number of lymphocytes in lamina propria. Some features, including intraepithelial lymphocytes in surface or crypt epithelium; and neutrophils, eosinophils, and edema in lamina propria, did not demonstrate significant difference in A-GVHD and negative controls. Pericryptal apoptosis, dilated crypts, irregular distribution of crypts, decreased lymphocytes, increased microvessel network, focal fibrosis, presence of muciphages, reactive changes in surface epithelium with mucin depletion, mucosal ulceration, and/or reduced mucosal thickness showed higher association with A-GVHD group. CONCLUSIONS: Intracyptal apoptosis is a reliable indicator of A-GVHD. Its diagnostic significance was improved if intracyptal apoptosis was associated with features which were observed more frequently in A-GVHD group as mentioned above.

Acute Disease↗
PubMed2003

Subcutaneous plasmacytomas with tropism to sites of previous trauma in a multiple myeloma patient treated with an autologous bone marrow transplant.

We report the case of a 59-year-old woman with Durie-Salmon stage IIIB IgGkappa multiple myeloma (MM), who presented 83 days after autologous hematopoietic stem cell transplant (HSCT) with multiple subcutaneous plasmacytomas. These lesions were confined exclusively to sites where the patient had sustained local trauma. The patient had no pre-transplant history of extramedullary disease and no evidence of plasma cells in the peripheral blood at any time throughout the course of her disease. This case represents the first report of refractory MM presenting as multiple subcutaneous plasmacytomas with specific tropism to sites of previous trauma. Selection of tumor cell subclones with unique chemokine receptor expression profiles that may explain this clinical observation is discussed.

Bone Marrow Transplantation↗
PubMed2003

Immunostaining of cytology smears: a comparative study to identify the most suitable method of smear preparation and fixation with reference to commonly used immunomarkers.

As an extension of our previous study (Shidham et al., Acta Cytol 2000;44:1015-1022), we evaluated the interference by methods of cytology smear preparation on the immunoreactivity of cytokeratin-7, cytokeratin-20, estrogen receptor, progesterone receptor, chromogranin, synaptophysin, and vimentin. Scrape cytology smears of 34 fresh specimens submitted for intraoperative consultation were studied. They were processed by three different methods--A: wet-fixed in 95% ethanol; B: air-dried saline rehydrated smears fixed in alcoholic formalin; and C: air-dried saline rehydrated smears fixed in 95% ethanol with 5% acetic acid. The intensity scores of immunostaining were estimated semiquantitatively and compared with corresponding formalin-fixed paraffin-embedded tissue sections (FPTS). Except vimentin, all immunomarkers showed higher intensity scores with method A or B than with method C. Vimentin showed the best results with method A. Our results indicate that the immunoreactivity pattern with each immunomarker is affected by the method of cytology smear processing. Most importantly, method C, which is the desired choice for cytomorphological staining, was not suitable for immunostaining.

Biomarkers, Tumor↗
PubMed2003

Mantle cell lymphoma of the hard palate: a case report and review of the differential diagnosis based on the histomorphology and immunophenotyping pattern.

To our knowledge, mantle cell lymphoma (MCL) has never been reported in the hard palate, but it is commonly observed in the nasopharynx and Waldeyer's tonsillar ring. MCL is characterized by a diffuse infiltrate of small lymphocytes with the expression of CD5, CD20, and cyclin D1 (Bcl-1), but not CD10. MCL presenting in the hard palate must be accurately distinguished from other forms of so-called small B-cell lymphomas-such as small lymphocytic lymphoma, follicular lymphoma, and extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue-because MCL possesses a worse prognosis. Awareness of MCL of the hard palate will prompt pathologists to perform adequate immunohistochemical analysis to aid in confirming the diagnosis.

Antigens, CD↗
PubMed2003

Molecular genetics of pediatric soft tissue tumors: clinical application.

The application of molecular genetics to pediatric soft tissue tumors has grown tremendously over the last decade. It has resulted in the identification of novel genes that have provided us with an increased understanding of oncogenesis. Furthermore, these findings have identified diagnostic and potentially prognostic factors for patient management. Molecular diagnostic techniques, such as reverse transcription PCR (RT-PCR) and fluorescence in situ hybridization (FISH), have become important tools for evaluating pediatric soft tissue tumors. By detecting characteristic fusion genes, these techniques have greatly increased the diagnostic accuracy of histopathological classification. One of the exciting promises of the development of these molecular techniques is their ability to detect micrometastasis and minimal residual disease. Monitoring of minimal residual disease in pediatric soft tissue tumors by quantitative RT-PCR may provide important prognostic information. Furthermore, the potential development of targeted therapy based on the understanding of the molecular pathology of a specific soft tissue tumor may complement existing treatments and improve disease outcome.

Child↗
PubMed2003

Humanized anti-CD20 monoclonal antibody (Rituximab) treatment for post-transplant lymphoproliferative disorder.

INTRODUCTION: Post-transplant lymphoproliferative disorders (PTLD) is a consequence of Epstein-Barr virus (EBV) infection and is a B-cell hyperplasia with CD-20 positive lymphocytes. The treatment of PTLD includes reduction/withdrawal of immunosuppression and chemotherapy. This study reports our center experience with humanized monoclonal antibody against CD-20 (Rituximab) for the treatment of PTLD. MATERIAL AND METHODS: Eight cases of PTLD after solid organ transplantation [six kidney, one kidney/pancreas (KP) and one liver] occurred between September 1998 and October 2001. The mean time between transplant and the diagnosis of PTLD was 57.3 months (range 3 months to 10 yr). Five patients underwent cadaveric transplant, five males and six were Caucasians with mean age of 48 yr (range 20-67 yr). RESULTS: The clinical presentation was as follows: lymphadenopathy--5, gastrointestinal bleeding--2 and tonsillar enlargement--1. The diagnosis was made by a lymph node biopsy in five, a gastric ulcer biopsy in two and a tonsillar biopsy in one case. Six of them had polymorphous, two had monoclonal B-cell lymphoma, and all were positive for CD-20. Six were related to EBV, documented by latent membrane protein (LMP) or Epstein-Barr encoded RNA (EBER) staining. Immunosuppression at the time of PTLD diagnosis consisted of tacrolimus in six cases and cyclosporine A (CsA) in two with mycophenolate mofetil (MMF) and azathioprine--3 each and sirolimus--1. Rituximab was administered at a dose of 375 mg/m2 once a week for 4 wk. There were no side effects seen with this therapy. Immunosuppression was reduced in all patients. Complete remission was observed in seven cases (one required two courses). One patient who did not respond received chemotherapy. Patients were followed for a mean period of 22.5 months (range 10-45 months post-PTLD diagnosis. At the last follow-up all eight patients were alive, seven with a functioning graft and one on maintenance dialysis. Three of these patients had been in remission for more than 2.5 yr. CONCLUSION: Rituximab is an effective agent in the treatment of PTLD without the morbidity characteristic of chemotherapy. Chemotherapy should be reserved only for those refractory to Rituximab therapy.

Adult↗
PubMed2003

Relative importance of CD38 expression over myeloid-associated markers expression in predicting the clinical course of B-CLL patients.

Expression of CD38 or myeloid-associated markers has been reported to be important in predicting prognosis in B-cell chronic lymphocytic leukemia (B-CLL) in separate studies but the impact of combining these markers on prognosis has not been examined. The current study aimed to evaluate the relative contribution of expression of CD38 and/or myeloid-associated markers (CD11b, CD13, CD15 and CD33) by flow cytometry (FCM) on the clinical course of 24 B-CLL patients. B-CLL patients with high levels of CD38 expression, defined as greater than or equal to 30% of neoplastic lymphocytes expressing CD38, had a significantly poorer OS than those with low levels of CD38 expression (54% cumulative survival: 51 months vs. 103 months, Kaplan-Meier survival analysis, p < 0.005, Logrank test). High levels of expression of myeloid-associated markers showed no statistically significant impact on OS in these patients. Ten of 11 patients (91%) with high levels of CD38 expression required chemotherapy. In contrast, only 5 of 13 patients (38%) with low levels of CD38 expression required chemotherapy (p < 0.009, Chi Square). There was no significant difference in the requirement for chemotherapy between patients with high levels of expression of myeloid-associated marker and those without (5/8 or 63% vs. 10/16 or 63%). Thus, our results suggest that CD38 is superior to myeloid-associated markers in predicting the prognosis of patients with B-CLL. Further studies with a larger sample size are indicated to confirm our observation.

ADP-ribosyl Cyclase↗
PubMed2003

Follicular hyperplasia, follicular lysis, and progressive transformation of germinal centers. A sequential spectrum of morphologic evolution in lymphoid hyperplasia.

We studied mantle B-cell and T-cell ingression in hyperplastic follicles (HFs), follicular lysis (FL), and progressive transformation of germinal centers (PTGC) in 19 paraffin-embedded, H&E-, bcl-2-, CD20-, and CD3-stained lymph nodes. We enumerated the T cells (CD3+) and mantle B cells (bcl-2+/CD3-) per 100 cells in 5 high-power fields of each entity (mean +/- SD). Compared with HF, FL had increased numbers of T cells migrating into germinal centers (39.8 +/- 10.0 vs 25.8 +/- 7.8; P < .0001). and a mild increase of mantle B cells (12.3 +/- 11.4 vs 2.1 +/- 1.6; P < .001). PTGC showed an increase of T-cell ingression compared with HF (36.5 +/- 12.1 vs 25.8 +/- 7.8; P < .0001) and more migration of mantle B cells into the follicle than FL (41.0 +/- 22.5 vs 12.3 +/- 11.4; P < .0001). T cells and mantle B cells ingress in FL and PTGC, although the mantle B-cell component predominates in the latter, suggesting that follicular hyperplasia, FL, and PTGC constitute an evolutionary spectrum in resolution of lymphoid hyperplasia with sequential ingression of T cells followed by mantle B cells. The maintenance of bcl-2 expression in mantle B cells in PTGC may cause differential diagnostic pitfalls in florid PTGC vs follicular lymphoma, particularly the so-called floral variant.

B-Lymphocytes↗
PubMed2003

Monocytes with altered phenotypes in posttrauma patients.

CONTEXT: Posttrauma patients show impaired immune responsiveness and increased susceptibility to infections. Although monocytes in these patients have been known to express decreased HLA-DR, induction of HLA-DR using interferon gamma failed to reduce susceptibility to infection, suggesting additional factors also may be involved in the impaired immune responsiveness. CD4 plays an integral role in most of the functions of HLA-DR. In newborn infants, who have impaired immune responsiveness, we found a concomitant reduction of CD4 on monocytes with decreased HLA-DR expression. OBJECTIVE: Because monocytes in posttrauma patients have not been previously studied for morphology, coexpression of CD4 and HLA-DR, and activity of alpha-naphthyl butyrate esterase, the purpose of this study was to analyze these factors in this population. DESIGN: Monocyte morphology; expression of CD4, CD11b, CD13, CD16, and HLA-DR by 3-color flow cytometry; and analysis of alpha-naphthyl butyrate esterase activity by cytochemical staining were studied in 27 posttrauma patients and 20 control subjects. RESULTS: Monocytes in posttrauma patients showed significant differences in the following characteristics compared with controls: (1) increase of subsets displaying the phenotypes CD4-/CD14+/HLA-DR- and CD4-/CD14+/CD16-, (2) decrease in mean fluorescence intensity of CD4 and HLA-DR expression in monocytes that were positive for these markers, (3) decrease in alpha-naphthyl butyrate esterase activity, and (4) decreased amount of cytoplasm and cytoplasmic vacuoles.Conclusion.-Our study suggests that in posttrauma patients, as in newborns, there is a marked increase of monocytes with decreased expression of CD4 and HLA-DR, as well as decreased alpha-naphthyl butyrate esterase activity. Concomitant reduction in CD4 and HLA-DR expression on monocytes may contribute to impaired immune responsiveness in these patients.

Accidents, Traffic↗
PubMed2003

Expression of p53, c-Myc, or Bcl-6 suggests a poor prognosis in primary central nervous system diffuse large B-cell lymphoma among immunocompetent individuals.

CONTEXT: Primary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL) in immunocompetent individuals, although rare, has been rising in incidence. Currently, no reliable prognostic markers are available for these individuals. OBJECTIVE: To study the implications of expression of a panel of oncogenic proteins (Bcl-2, Bcl-6, and c-Myc) and p53 for predicting clinical outcome, particularly overall survival, in immunocompetent individuals with primary CNS DLBCL. DESIGN: Fourteen primary CNS DLBCL cases were retrospectively studied by immunohistochemistry on formalin-fixed, paraffin-embedded sections for the expression of c-Myc, Bcl-2, Bcl-6, and p53. RESULTS: The overall frequencies of expression for p53, c-Myc, Bcl-2, and Bcl-6 in these cases were 29%, 50%, 71%, and 57%, respectively. Cases with expression of p53, c-Myc, or Bcl-6 had a poorer overall survival than those without (Kaplan-Meier survival analysis: 50% cumulative overall survival, 2 months vs 30-60 months, P =.02, log-rank test; 9-16 months vs 21-60 months, P =.03, log-rank test; and 9-16 months vs 21-60 months, P =.16, log-rank test, respectively). The expression of Bcl-2 or proliferation activity by MIB-1 showed no correlation with overall survival. Likewise, the clinical parameters, including age, location of tumors, multiplicity of tumor lesions, and lactase dehydrogenase levels revealed no impact on overall survival. CONCLUSION: Our results suggest that patients with expression of p53, c-Myc, or Bcl-6 have a poorer overall survival than those without. Since traditional prognostic markers in non-CNS DLBCL, such as staging and International Prognostic Index scores, are not applicable to primary CNS DLBCL, evaluation of p53, c-Myc, and Bcl-6 by immunohistochemistry may be warranted as part of prognostic evaluation in immunocompetent patients with primary CNS DLBCL. Further studies are indicated to confirm our observations.

Adult↗
PubMed2003

Pharmacogenomics as an aspect of molecular autopsy for forensic pathology/toxicology: does genotyping CYP 2D6 serve as an adjunct for certifying methadone toxicity?

Pharmacogenomics, applied as an aspect of molecular autopsy, may be used as an adjunct for certifying methadone fatalities. Methadone is metabolized by cytochrome P-450 (CYP) 1A2, 3A4, and 2D6. We hypothesized that methadone toxicity may be partially due to CYP 2D6 *3, *4, and *5 variant alleles, resulting in poor drug metabolism. A retrospective analysis was performed on covariables and risk factors of 21 methadone cases from the Milwaukee County Medical Examiner's Office (1998-2000). PCR genotyping showed: one heterozygous for 2D6*3, two homozygous for 2D6*4, five heterozygous for 2D6*4, and one heterozygous for both 2D6*3 and *4. This limited number of cases showed that the prevalence of poor metabolizer was higher but not significantly different from that of a control group (n = 23) (P > 0.05, Fisher Exact Test). Thus, CYP 2D6 mutations may not yet be directly associated with methadone toxicity. However, pharmacogenomics, complementing other case findings, served as an adjunct in interpreting methadone toxicity of poor and intermediate metabolizers.

Adult↗
PubMed2002

Expression of MUM1/IRF4 correlates with clinical outcome in patients with B-cell chronic lymphocytic leukemia.

In this study, we evaluated the prognostic significance of multiple myeloma-1/interferon regulatory factor-4 (MUM1/IRF4) expression in B-cell chronic lymphocytic leukemia (B-CLL). Our results demonstrated that the absence of MUM1/IRF4 expression showed the highest relative risk among the factors analyzed in determining the probability for death in patients with B-CLL using univariate and multivariate Cox regression analysis. Patients without MUM1/IRF4 expression had significantly worse overall survival than did those with MUM1/IRF4 expression (52% cumulative survival, 63 months vs not reached, Kaplan-Meier survival analysis; P <.03, log-rank test). Patients with MUM1/IRF4 expression were more likely to have disease at low Rai stage and interstitial/nodular marrow involvement. Furthermore, only 1 of 11 patients with MUM1/IRF4 expression and interstitial/nodular marrow involvement died during a 100-month follow-up. Our results suggest that B-CLL with expression of MUM1/IRF4, indicative of postgerminal center origin, has a more favorable clinical course and that MUM1/IRF4 is an important prognostic marker in B-CLL.

Adult↗
PubMed2002

Clinical, histopathologic, and biologic features of pleomorphic lobular (ductal-lobular) carcinoma in situ of the breast: a report of 24 cases.

We reviewed 10 cases of pleomorphic lobular (ductal lobular) carcinoma in situ (PL/DLCIS) of the breast and compared them with 14 cases of pleomorphic lobular carcinoma in situ (PLCIS) found in association with invasive pleomorphic lobular carcinoma. The histologic features; immunohistochemical staining for estrogen receptors (ERs), p53, Ki67, E-cadherin, and gross cystic disease fluid protein-15 (GCDFP-15); and results of fluorescence in situ hybridization for HER-2/neu gene amplification were evaluated in all 24 cases. Histologically, PL/DLCIS cells were similar to those of PLCIS with invasion in that they were discohesive and medium to large in size with moderate to marked nuclear pleomorphism, small to prominent nucleoli, and moderate to abundant eosinophilic or vacuolated cytoplasm. In both groups, central necrosis was present in a small number of cases, and classic LCIS coexisted with the in situ lesion in less than half of the cases; in situ carcinomas were positive for ERs in 23 (100%) of 23 cases, p53 in 6 (25%) of 24 cases, and GCDFP-15 in 14 (74%) of 19 cases. The percentage of Ki67-positive tumor nuclei indicated moderate to high (more than 20%) proliferative activity in 8 (47%) of 17 cases. Immunostaining for E-cadherin was negative in all 24 cases. HER-2/neu gene amplification was observed in 1 (4%) of 23 cases. In cases with associated invasion, PLCIS had cytologic features and immunostaining patterns similar to those of the invasive pleomorphic component. Seven of the 10 patients who had PL/DLCIS without invasion underwent lumpectomy or simple mastectomy. Six of these patients had no evidence of disease in follow-up periods ranging from 4 to 32 months; the seventh patient developed recurrent disease 12 months after undergoing lumpectomy. We conclude that the cytologic features and biomarker expression profile of PL/DLCIS are similar to those of PLCIS with invasion but somewhat different from those of classic LCIS and ductal carcinoma in situ. Long-term follow-up studies are needed to further define the natural history of PL/DLCIS and its optimal management.

Adult↗