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W C Chan

Publications and source records attributed to W C Chan.

At least 19 recordsLinked to original sources
PubMed2026

Methylation profiling of normal tissue adjacent to breast tumors reveals two distinct groups with divergent tumor microenvironment features.

We previously identified diverse genetic evolutionary patterns in whole-genome sequencing of paired normal tissue adjacent to tumor (NAT) and tumor tissues from Hong Kong breast cancer (HKBC) patients. Here, we investigated whether DNA methylation (DNAm) contributes to NAT heterogeneity and shapes the tumor microenvironment (TME). Genome-wide DNAm profiling was performed on paired NAT and tumor tissues from 188 HKBC patients using the Infinium 850 K array. RNA-seq data were available for 76 NATs and 177 tumors. Cellular composition was inferred using MethylCIBERSORT, CIBERSORTx, and EpiDISH, and histopathologic features were assessed on 115 H&E-stained sections. Unsupervised clustering identified two distinct NAT subtypes with divergent TME characteristics. Cluster 1 (N = 139) showed higher epithelial and fibroblast content and enrichment of estrogen response pathways. Cluster 2 (N = 49) exhibited an immune-metabolic phenotype characterized by increased fat and immune cells, stromal disruption, inflammatory pathway activation, and greater macrophage infiltration. Cluster 2 patients also demonstrated significantly younger epigenetic age estimated using multiple epigenetic clocks. These DNAm-defined NAT subtypes and associated TME features were validated in 97 NAT samples from TCGA breast cancer patients. Overall, our findings identify DNAm-driven NAT heterogeneity with distinct TME landscapes, providing new insights into field cancerization and tumor evolution in breast cancer.

Journal Article↗
PubMed1995

Transcripts of the npm-alk fusion gene in anaplastic large cell lymphoma, Hodgkin's disease, and reactive lymphoid lesions.

Anaplastic large cell lymphoma (ALCL) and Hodgkin's disease (HD) have some pathologic and immunohistochemical similarities, and a histogenetic relationship between them has been suggested by some investigators. By cytogenetic study, the t(2;5)(p23;q35) translocation appears to be unique for ALCL. The breakpoints of the t(2;5)(p23;q35) have recently been cloned and are reported to involve a novel tyrosine kinase gene, anaplastic lymphoma kinase (alk), on chromosome 2 and the nucleophosmin gene (npm) on chromosome 5. Therefore, we studied the frequency of npm-alk translocation in ALCL using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay. We also studied HD and a variety of reactive lymphoid lesions since there is contradictory information in the literature on the occurrence of the npm-alk rearrangement in HD. We detected npm-alk hybrid mRNA in 8 of 22 cases of ALCL (36%), but none of the 21 cases of HD or the 11 cases with reactive lesions contained amplifiable template. All positive ALCL had the T or indeterminate phenotype and occurred in young adults or children. There was very good correlation between a cytogenetically detectable t(2;5) and a positive signal by RT-PCR. Our results indicate a selective but relatively infrequent association between the t(2;5) and ALCL of T or indeterminate phenotype, not shared with HD or reactive hyperplasia.

Adolescent↗
PubMed1995

Clonal relationship between lymphocytic predominance Hodgkin's disease and concurrent or subsequent large-cell lymphoma of B lineage.

The occurrence of a large-cell lymphoma (LCL) concurrent with or subsequent to lymphocytic predominance Hodgkin's disease (LPHD) is well documented. Given the well-characterized B-cell nature of the Reed-Sternberg cell variants in LPHD, there may be a clonal relationship between the LPHD and the associated B-cell LCL. In this study, we adapted a highly sensitive, clonospecific assay to test whether the clone comprising the LCL exists in the corresponding LPHD tumor. Nine cases meeting the histologic criteria of nodular LPHD and B-cell LCL were identified, reviewed, and studied. Initially, clonality of both lesions was assessed using consensus primers to conserved regions in the IgH variable (frame-work III) and joining region genes in a polymerase chain reaction (PCR) assay. The PCR assay detected a clonal B-cell population in five of the LCLs, whereas analysis of eight cases of LPHD did not detect a dominant clone. Clonal products from the LCL were then sequenced, and clonospecific oligonucleotides were designed from the unique nucleotide sequence encoding the complementarity-determining region-III. These were then used as primers and/or probes in sensitive PCR-based assays on the corresponding LPHD tumors. In two cases, the clonospecific assay showed that the LPHD and LCL shared a common clone that was further confirmed by sequence analysis. This finding provides genotypic evidence that, at least in some cases, the LCL represents a clonal progression of LPHD.

Adult↗
PubMed1995

Prognostic value of cellular proliferation and histologic grade in follicular lymphoma.

The clinical usefulness of histologic grading in follicular lymphoma (FL) is controversial and is further compromised by the subjective nature and poor reproducibility of most systems in current use. Therefore, we decided to objectively evaluate the importance of cellular proliferation in FL, along with the current grading systems. We studied 106 patients with FL who were uniformly staged and aggressively treated. A proliferative index (PI) was determined quantitatively using an automated image analyzer and a new Ki-67 antibody that stains archival paraffin tissues. The cases were also subclassified according to the Berard, Rappaport, Luke-Collins, and Jaffe methods, and survival analysis was performed. Patients with a low PI (< 40%) had a significantly longer overall survival (OS) than those with a high PI (> or = 40%), but the PI did not predict failure-free survival (FFS). The mean PI correlated well with the subgroups in each of the various classifications. All four of the classification methods were predictive of OS, but only the Berard method appeared to predict FFS and suggest that a proportion of patients with FL may be curable. In multivariate analysis, histologic classification was the only independent predictor of OS (Berard method: relative risk, 3.1) and the International Prognostic Index was the only independent predictor of FFS (relative risk, 2.3). We conclude that the Berard method for grading of FL is clinically useful and, along with the International Prognostic Index, should be included in future clinical studies of FL. The measurement of cellular proliferation does not appear to add additional useful information in FL.

Adult↗
PubMed1995

Acute agranular CD4-positive natural killer cell leukemia. Comprehensive clinicopathologic studies including virologic and in vitro culture with inducing agents.

BACKGROUND: A 63-year-old male presented with fever, a subcutaneous nodule, gingival hypertrophy, lacrimal gland enlargement, and no lymphadenopathy or hepatosplenomegaly, but had anemia, thrombocytopenia, and peripheral blood (PB) plus bone marrow (BM) involvement by leukemic cells. There was minimal response to multiagent chemotherapy and local radiotherapy, with a survival of 6.5 months from disease diagnosis. METHODS: The PB and/or BM leukemic cells were evaluated using electron microscopy (EM), immunohistochemistry, flow-cytometric immunophenotyping, cytochemistry, cytogenetics, Southern blot analysis for gene rearrangement and Epstein-Barr virus (EBV), polymerase chain reaction for EBV and human herpes virus-6 (HHV-6), and in vitro culturing with inducing agents. RESULTS: The leukemic cells were agranular and monocytoid, with a hairy cell-like bone marrow biopsy infiltrate. Myeloperoxidase (MPO) and alpha-naphthyl butyrate esterase staining was negative, and periodic acid-Schiff staining was positive by light microscopy. Electron microscopy showed MPO negativity and a lack of parallel tubular arrays. The immunophenotype was CD3-, CD56+, CD4+, CD8-, CD15+, TCR1-, and TCR2-, with germline immunoglobulin and T-cell receptor genes and an abnormal karyotype (44XY, 5q-, -13, 13q+, -15). No genomic material for EBV or HHV-6 was detected. Cell cultures with butyrate and N,N-hexamethylene bis-acetamide suggested the possible induction of tumor cells to express a T-cell immunophenotype. CONCLUSION: A case of clonal acute natural killer (NK) cell leukemia with an unusual morphology (agranular) and unique phenotype (CD3-, CD56+, CD4+, CD15+) is presented. Unlike as in other acute NK leukemias, EBV was negative; there was no evidence of HHV-6. The tumor cell, after culturing with differentiating agents, may have been induced to express a T-cell immunophenotype.

Acetamides↗
PubMed1995

T-cell-rich B-cell lymphoma. A clinicopathologic study of eight cases.

Although T-cell-rich B-cell lymphoma (TCRBCL) is a recently recognized form of non-Hodgkin's lymphoma (NHL), limited information regarding its incidence, cellular origin, morphologic spectrum, and biologic behavior is currently available. In this study, the clinicopathologic features of eight patients with TCRBCL are presented. This neoplasm comprised about 1% of all NHLs seen at Emory University Hospital over 2 years. The male-to-female ratio was 1.6, and the mean age at diagnosis was 60 years. At presentation, TCRBCL was nodal in 88% of the patients and widely disseminated in 50% of the patients. A complete remission was seen in three of the five patients treated with combination chemotherapy that was directed at intermediate grade NHL. Three patients received inadequate or incomplete chemotherapy. One of these patients later achieved a complete remission with more intensive therapy. Two of the patients were not evaluable for response to therapy. The actuarial and disease-free survival rates of the group at 5 years were 72% and 21%, respectively. Morphologically, the lymph nodes in seven of eight cases were diffusely obliterated, whereas one had markedly expanded interfollicular zones that lead to an initial diagnosis of T-zone lymphoma. All tumors were characterized by no more than 25% large lymphoid cells, which were scattered in a background of small lymphocytes with round or irregular nuclei. The presence of numerous histiocytes imparted a lymphoepithelioid appearance in two cases. Although immunoperoxidase stains of frozen tissue were initially suggestive of a peripheral T-cell lymphoma in some cases, paraffin immunoperoxidase stains clearly established the B-cell nature of the large cells, whereas most of the small cells were T lymphocytes. The clonal nature of the large cells was confirmed in seven cases by monotypic immunoglobulin (Ig) light chain restriction or Ig gene rearrangements. Epstein-Barr virus genomic DNA was detected in two of the six cases tested by polymerase chain reaction or Southern blot analysis, but no evidence of a bcl-2 rearrangement was found in any of the five cases examined. These findings indicate that TCRBCL is an uncommon form of NHL with a therapeutic response and overall survival consistent with intermediate grade lymphoma. Paraffin immunoperoxidase stains and occasionally genotypic analysis are required to exclude the diagnosis of PTCL or diffuse lymphocyte predominant Hodgkin's disease. The authors found no morphologic or molecular evidence to support a follicular center cell origin in these cases of TCRBCL.

Adult↗
PubMed1995

How U.S. radiologists use their professional time: factors that affect work activity and retirement plans.

PURPOSE: To determine what demographic, professional, and practice characteristics are related to the amount of time radiologists work per week, to their allocation of time among professional activities, and to their plans for retirement. MATERIALS AND METHODS: The American College of Radiology surveyed 2,804 radiologists and nuclear medicine specialists. Means and percentiles were calculated for the radiologists' number of hours and days worked per week, number of weeks away, percentage allocation of time, and retirement intentions. Multiple linear and logistic regression analyses were performed. RESULTS: Full-time, post-training radiologists worked a mean of 50 hours per week. Radiologists spent 2 weeks on professional education and 4.4 weeks on vacation each year. On average, 68% of professional time was spent on hospital patient care; 18%, on office patient care; 7%, on teaching and research; and 5% on administration. Forty-one percent of radiologists planned to eventually work part-time; 47% intended to retire fully. CONCLUSION: These data will provide an important baseline for modeling the future size of the radiologist workforce and for assessing changes in the ways radiologists use their time and plan their futures.

Adult↗
PubMed1995

U.S. radiologists' satisfaction in their profession.

PURPOSE: To determine characteristics associated with differences among radiologists in professional satisfaction and the effect of satisfaction on career plans. MATERIALS AND METHODS: The American College of Radiology surveyed 2,804 radiologists and nuclear medicine specialists in the United States. Single-variable and multivariate analyses were performed. RESULTS: Sixty-five percent of radiologists were currently satisfied with their profession; 31% were more satisfied than they were 5 years ago, 32% felt the same, and 37% were less satisfied. Current satisfaction was most likely for radiologists with a diagnostic radiology subspecialty, board certification, age over 45 years, an academic practice, a salaried position, a full-time practice, urban location, and location in the West. Professional satisfaction relative to that 5 years ago was particularly high for (among others) young radiologists. Poorly satisfied radiologists were more likely to plan a career change and eventual part-time work. Female radiologists were as satisfied as males. CONCLUSION: This study identifies sources of radiologists satisfaction and dissatisfaction and effects of satisfaction on career plans.

Adult↗
PubMed1995

Clinical and prognostic significance of bone marrow involvement in patients with diffuse aggressive B-cell lymphoma.

PURPOSE: We studied the effect of morphology and extent of bone marrow (BM) infiltrate on the survival of patients with diffuse aggressive B-cell non-Hodgkin's lymphoma (NHL), along with clinical features. PATIENTS AND METHODS: Sixty adult patients with diffuse aggressive B-cell NHL and BM involvement at the time of presentation were studied. All patients were uniformly staged and treated with a curative high-dose chemotherapy regimen. BM involvement was assessed according to the cytology, pattern of infiltration, and extent of involvement, and was correlated with overall survival (OS) and failure-free survival (FFS). RESULTS: Patients with BM involvement that consisted of > or = 50% large cells or BM involvement of > or = 70% had a poorer OS (P = .065 and P = .055, respectively). Those who presented with an infiltrate of less than 50% large cells and an international prognostic index (IPI) of < or = 3 had a significantly longer postrelapse survival time (P = .003). A diffuse or interstitial pattern of BM involvement was predictive of both poor OS and FFS (P = .008 and .009, respectively). Multivariate analysis indicated that only IPI (P = .0005) and pattern of BM infiltration (P = .009) were independent predictors of OS, and only the former was predictive of FFS (P = .03). CONCLUSION: The IPI is predictive of OS and FFS, while BM involvement with a diffuse or interstitial pattern is associated with significantly poorer OS. Patients with BM infiltration that involved > or = 70% of the marrow or contained > or = 50% large cells had poor OS, but more patients need to be studied to determine the significance. Two parameters, IPI < or = 3 and BM large cells less than 50%, identify a group of patients with long-term survival after relapse.

Adult↗
PubMed1995

The employment market for diagnostic radiologists and radiation oncologists: an update.

OBJECTIVE: In response to concern throughout the profession about the employment market for radiologists in the United States, the American College of Radiology, through several information-gathering activities, is monitoring the situation, including the amount of hiring done, job vacancies, and unemployment. To provide context, we compare our findings with data for earlier years and for all physicians. MATERIALS AND METHODS: The American College of Radiology undertook systematic sample surveys of approximately 60 training program directors with regard to their graduates; 3000 radiologists with regard to unemployment; and 400 radiology groups with regard to hiring. Good response rates (> or = 70%) were achieved; separate data for radiation oncology and diagnostic radiology are generally available. Data on use of the College's placement service also are presented. RESULTS: Among trainees completing a diagnostic radiology fellowship or a radiation oncology residency in 1994, 1% (standard error = 1%) were unemployed in December 1994 and 15% (standard error = 4%) were working in jobs not in keeping with their training and employment goals. Among all radiologists, the 1994 unemployment rate was 0.5% (standard error = 0.2%). Radiology groups were hiring for approximately 1600 positions in 1994, of which about three fifths were replacements and two fifths were expansions. After hiring was completed, remaining vacancies numbered approximately 400, or 2% of the radiology workforce. In early 1995, program directors reported that trainees completing a residency or fellowship in 1995 were having greater difficulty finding positions than had their 1994 counterparts. CONCLUSION: The unemployment rate for radiologists was similar to that for all physicians and lower than that for other persons with advanced degrees (1.5-2%). In 1994, expansion positions for which groups were hiring nearly equaled the growth of the radiology workforce. However, 1994 hiring (and vacancy) rates were only approximately 70% of 1991 levels. It is clear that the employment market is weakening; however, contrary to some anecdotal reports, a large-scale collapse has not occurred.

Employment↗
PubMed1995

The sex ratio of American radiologists: comparison and implications by age, subspecialty, and type of practice.

OBJECTIVE: The purpose of this paper is to present results related to two questions regarding changes in the sex ratio of American radiologists. Do men and women in radiology have different patterns of subspecialization, postresidency training, board certification, or practice characteristics? Do differences in patterns between the sexes imply that the number of radiologists required in the future will change with a changing sex ratio of radiologists? MATERIALS AND METHODS: A survey questionnaire was mailed to a stratified random sample of 2804 radiologists, radiation oncologists, and nuclear medicine specialists drawn from the American Medical Association Physician Masterfile. The survey achieved a response rate of 69%. Stratification criteria included sex, age, and subspecialty. The survey questions included age, sex, subspecialty, training status, board certification, type of practice, principal work activity, source of income, hours worked, and amount of time away from the practice. Data analysis used descriptive statistics, ordinary least squares regression, and logit analysis. Weighting assured that results represent all radiologists. RESULTS: Only 13% of active radiologists who have finished training are women. The percentage varies with age; 6% of radiologists 45 years old or older; 22% of those 35-44 years old, and 23% of those younger than 35 years old were women. Differences in the sex ratio were not associated with differences in board certification or postresidency fellowships, but subspecialization differed by sex. Women were more likely than men to be salaried, to work part-time, to be engaged in teaching, and to work in an office rather than in a hospital. Differences in the sex ratio had little impact on estimates of the number of radiologists that will be needed in the future. CONCLUSION: Female radiologists have subspecialization and practice characteristics different from those of male radiologists. The increasing percentage of women in the profession will have little effect on the number of radiologists and radiation oncologists needed.

Adult↗
PubMed1995

Juvenile scleroderma: report of a case.

Scleroderma is a rare connective tissue disease in children. A 12-year-old boy suffered from progressive increasing skin tension with erythematous changes in his left leg for a period of 3 months. This limited the range of motion in his left first and second metatarsophalangeal joints. A skin biopsy showed hypertrophic collagen bundles with atrophic skin appendages and lymphocytic infiltration. Based on the clinical manifestations and typical histopathologic findings, juvenile linear scleroderma was diagnosed. He was successfully treated with a short course of oral prednisolone in addition to long-term therapy with D-penicillamine and a topical emollient.

Child↗
PubMed1995

Aggressive natural killer cell lymphoma of the small intestine.

We report a case of aggressive non-Hodgkin's lymphoma of the small cell type arising in the small intestine and having a natural killer cell phenotype. Immunophenotyping of frozen tissue sections revealed a lack of reactivity with the pan-T-cell markers CD3 and CD5, and no reaction with B-cell markers. Positive staining was obtained with antibodies to CD2, CD7, and CD56. Molecular studies were negative for clonal T gamma, T beta and immunoglobulin heavy-chain gene rearrangements. Natural-killer-cell-associated cytotoxin was demonstrated by positive staining with an antibody to perforin, a protein present in the granules of large granular lymphocytes. Despite its indolent histologic appearance, the aggressive nature of this neoplasm was suggested by the expression of the activation markers CD38 and CD71, and the nuclear proliferation marker Ki67, and confirmed clinically by its rapid recurrence with extensive involvement of the pelvic organs, resistance to chemotherapy, and the short survival of the patient. Distinct from many Asian cases, Epstein-Barr virus genome was not detectable in the tumor. This case emphasizes the importance of recognizing non-Hodgkin's lymphomas with a natural killer cell phenotype as a distinct entity, both biologically and clinically.

Biomarkers, Tumor↗
PubMed1994

Lymphocyte predominance Hodgkin's disease: lineage and clonality determination using a single-cell assay.

Lymphocyte predominance Hodgkin's disease (LPHD) is a clinically indolent condition. Although there is evidence that the putative neoplastic cell in this disease, the "L&H" cell, is of B-cell lineage, there is conflicting data concerning the clonality of these cells. Our study was aimed at clarifying the issue of lineage and clonality of the L&H cells of LPHD using a single-cell assay. Four cases of LPHD were studied. To circumvent the difficulties of obtaining fresh tissue and to be able to study representative cases, a new method was developed to obtain single-cell suspensions of L&H cells from archival formalin-fixed paraffin-embedded tissue. Single L&H cells were identified by morphology and immunostaining for epithelial membrane antigen, isolated using a micropipette, and subjected to polymerase chain reaction (PCR) amplification of the complematarity determining region 3 (CDR3) of the Ig heavy chain (IgH) gene, which is B-cell clone-specific. The PCR products were size-fractionated by polyacrylamide gel electrophoresis and representative products were directly sequenced. Single T cells and small B cells were also isolated from the tissues and used as negative and positive controls, respectively. In all four cases of LPHD, the IgH CDR3 of single L&H cells could be amplified. Within each case, the IgH CDR3 of single L&H cells was found to be of different length or of different sequence. Therefore, our results provide strong evidence for the B-cell origin of the L&H cells and the polyclonal nature of LPHD.

Antigens, CD↗
PubMed1994

T-cell receptor gene rearrangement in T-cell large granular leukocyte leukemia: preferential V alpha but diverse J alpha usage in one of five patients.

T-gamma lymphoproliferative disease (T-gamma LPD) is a chronic disorder of mature T cells that is associated with neutropenia and autoimmune phenomena. Although the progression of the lymphoproliferation is indolent, it is often associated with a monoclonal proliferation of T-cell-type large granular lymphocytes (LGL) that manifest multiple in vitro suppressor and cytotoxic activities. We considered the possibility that the granulocytopenia or anemia might represent an autoimmune disorder mediated by the monoclonal LGL via T-cell receptor (TCR) recognition of an antigen involved in hematopoiesis. Therefore, in an effort to characterize the usage of the TCR alpha- and beta-chain genes in patients with T-gamma LPD, we cloned and sequenced TCR alpha- and beta-chain mRNAs derived from the T-cell type LGL of five patients. The five patients studied did not use a common V alpha nor a common J alpha segment. However, an unusual finding was observed in one of the patients where the occurrence of a single variable-diversity-junctional (VDJ) rearrangement of the beta chain confirmed the monoclonal origin of the LGL proliferation. In accord with this evidence for monoclonality, many of the cells studied used a common V alpha (V alpha 19.1). In contrast to this common V alpha usage, there was a marked diversity of the J alpha segments and N-region addition that were associated with the V alpha 19.1 segment. This pattern of common V alpha usage associated with different N and J alpha segments suggests an immune-mediated selection process affecting the TCR alpha chain occurring after the transformation event that established the clone. We suggest that the T-cell-type LGL malignant clone might have developed autoreactivity conferred by the selected TCR alpha chain and that this autoreactivity might be implicated in this patient's anemia.

Amino Acid Sequence↗