Publications (12)46.13 Total impact
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Article: Serum amyloid A is elevated in the serum of lung cancer patients with poor prognosis.
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ABSTRACT: Lung cancer is known as the top cancer killer in most developed countries. However, there is currently no promising diagnostic or prognostic biomarker for lung cancer. This study aims to discover non-invasive differential markers in the serum of lung cancer patients, to determine the protein identity of the candidate biomarker(s), and to investigate any clinical implication of the biomarker(s) concerned. Blood specimens were collected from 154 pre-operative patients with lung cancer and 35 healthy blood donors with no evidence of lung cancer. Fractionated serum samples were processed by surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (MS). Candidate biomarker was identified using sodium dodecyl sulphate polyacrylamide gel electrophoresis and tryptic digestion followed by tandem MS fragmentation analysis, which was subsequently validated with immunoassay. A differential protein with m/z 11.6 kDa was detected and identified as an isoform of human serum amyloid A (SAA). It was significantly increased by 1822% in lung cancer patients when compared with the healthy controls, which gave an area under the receiver operator characteristic curve of 0.88. In addition, the protein was also significantly elevated by 77% in lung cancer patients with survival <5 years when compared with patients with survival > or =5 years. There are several functions of the SAA protein, described in the context of inflammation, that are compatible with the mechanism of tumour invasion and metastasis. Our study not only detected increased SAA level in the serum of lung cancer patients but also identified that elevated SAA level may be a non-invasive biomarker useful for the prediction of lung cancer prognosis.British Journal of Cancer 06/2010; 102(12):1731-5. · 5.04 Impact Factor -
Article: Remarkable application of serum EBV EBER-1 in monitoring response of nasopharyngeal cancer patients to salvage chemotherapy.
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ABSTRACT: Nineteen consecutive patients with metastatic or recurrent nasopharyngeal cancer (NPC) receiving combination chemotherapy were monitored for EBV DNA in their serum. EBV DNA (EBER-1) concentration in serum was measured before, during, and after chemotherapy. Thirteen patients had additional multiple prechemotherapy readings. There was a significant lead time from first detection of serum EBER-1 to clinical recurrence in 62% of patients by a mean of 17.4 weeks (range: 8-74.5 weeks; mean = 28.2 weeks if confined to the 8 patients with significant lead time). The median EBER-1 concentration was significantly higher in those with distant metastasis as compared to those with loco-regional recurrence only (17,468 vs. 684 pg/mL serum; p = 0.046, Mann-Whitney U test). Among the 13 patients who responded to chemotherapy, 4 exhibited clinical complete remission (CR) who were only found in the group with EBER-1 DNA drop to background level, while the magnitude of EBER-1 drop did not discriminate partial remission (PR) and stable disease (SD) patients clearly. Subsequent profile of EBER-1 DNA showed concordance with clinical course of either continuous remission or later progression. EBER-1 DNA in serum can become a useful adjunctive surrogate marker to monitor chemotherapeutic response in NPC patients with distant metastasis or advanced local recurrence.Annals of the New York Academy of Sciences 10/2001; 945:73-9. · 3.15 Impact Factor -
Article: Prognostic significance of DNA flow cytometric analysis in patients with nasopharyngeal carcinoma.
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ABSTRACT: Nasopharyngeal carcinoma (NPC) is a prevalent malignant tumor among Southern Chinese. Previously, the authors described the prognostic significance of a serum antibody assay to a recombinant Epstein-Barr virus Bam HI-Z replication activator protein (ZEBRA) in NPC patients with long term follow-up. In this study, the authors further reported the use of DNA flow cytometry (DNA-FCM) as an additional technique for determining the prognosis of NPC patients in the same series. One hundred and forty-three archival biopsies from 110 NPC patients were deparaffinized and subjected to DNA-FCM analysis. DNA ploidy state and various proliferative indices (PI) of the tumors were correlated with patient survival and frequency of recurrence. Among the biopsies analyzed, 119 were histologically positive NPC and 24 were negative. Fifty-one tumor biopsies that fulfilled the guideline criteria of the DNA Cytometry Consensus Conference were correlated with the clinical manifestations of the patients. Among them, 43 tumors (84%) were DNA diploid and 8 (16%) were aneuploid. Two PI, S-phase fraction (SPF) and proliferation fraction (PF), appear to be potentially useful prognostic indicators. For example, PF in patients who developed locoregional recurrence (15.1%) and distant recurrence (16.4%) after radiation therapy both were significantly higher than PF in patients who were in complete remission (8.2%) (P = 0.0005 and P = 0.004, respectively). Significant differences in SPF between patients with distant recurrence (10.6%) and those in remission (5.7%) also was found (P = 0.005). Using Kaplan-Meier analysis, patients with high PF, high SPF, and aneuploid tumors had significantly poorer 12-year survival rates (35%, 26%, and 28%, respectively) than those patients with low PF, low SPF, and diploid tumors (77%, 67%, and 59%, respectively) (P < 0.0009, P < 0.004, and P < 0.01, respectively). Determination of tumor PI and DNA ploidy state by DNA-FCM at diagnosis of NPC can be potentially useful in selecting a poor prognostic subgroup of NPC patients. These parameters may enable oncologists to plan for more stringent treatment strategies such as hyperfractionated and accelerated radiation therapy or concomitant chemoradiotherapy for these patients.Cancer 01/1999; 83(11):2284-92. · 4.77 Impact Factor -
Article: Basaloid-squamous carcinoma of the nasopharynx. An Epstein-Barr virus-associated neoplasm compared with morphologically identical tumors occurring in other sites.
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ABSTRACT: Basaloid-squamous carcinoma is a newly characterized, highly aggressive neoplasm occurring mostly in the base of tongue, hypopharynx, larynx, and esophagus. Its occurrence in the nasopharynx is rare. The clinicopathologic features of three cases of basaloid-squamous carcinoma of the nasopharynx are described and were studied for the presence of Epstein-Barr virus (EBV) by in situ hybridization for EBV-encoded small nuclear RNA (EBER). For comparison, basaloid-squamous carcinomas occurring in other sites also were studied for the presence of EBV. EBER was detected in all 3 cases of basaloid-squamous carcinoma occurring in the nasopharynx, but in none of the 13 cases from other sites including the esophagus, larynx, pharynx, hypopharynx, and nasal cavity. The nasopharyngeal basaloid-squamous carcinomas occurred in two male and one female patients with an age range of 48-70 years. The serum immunoglobulin A against the EBV-viral capsid antigen was elevated in all three cases. Two patients developed cervical lymph node involvement during the course of the disease. All three patients were treated by radiotherapy and survived for longer than 34 months compared with the average reported median survival of approximately 2 years for basaloid-squamous carcinomas occurring in the usual sites. Based on this limited study, basaloid-squamous carcinoma occurring in the nasopharynx appears to be an EBV-associated neoplasm, whereas the same tumor occurring in other sites is not. The prognosis is potentially better for patients with nasopharyngeal basaloid-squamous carcinoma, which appears to be pathogenetically and biologically more related to the much more common nasopharyngeal undifferentiated carcinoma.Cancer 12/1995; 76(10):1689-93. · 4.77 Impact Factor -
Article: Primary lymphoepithelioma-like carcinoma of the lung. A clinicopathologic study of 11 cases.
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ABSTRACT: Lymphoepithelioma-like carcinoma (LELC), best known to occur in the nasopharynx, can arise in a variety of sites, such as the salivary gland, thymus, lung, stomach, and skin. Primary LELC of the lung is very rare, with only limited information in the literature. The clinicopathologic features of 11 patients with pulmonary LELC collected from two regional hospitals in Hong Kong are described. The patients, all Chinese, were aged 38 to 73 years (median, 54 years), with equal sex incidence. Two of the 8 patients were smokers. Four presented with coin lesions incidentally discovered on chest X-ray, five with cough and blood-stained sputum, and two with pleural effusion. The tumor formed a discrete (9 patients) or an ill-defined (1 patient) nodule in the lung, or, rarely, showed extensive bilateral pulmonary involvement (1 patient). The major bronchi were not involved except in 1 patient. Three patients had lymph node metastasis at presentation; two of them had bone metastasis, one at presentation and one after 9 months. The tumors had pushing margins, and grew in the form of anastomosing islands and sheets, comprising syncytial-appearing large cells with vesicular nuclei and prominent nucleoli. They were infiltrated by an appreciable number of small lymphocytes and plasma cells. Intratumoral amyloid globules were found in one tumor. In five patients, the tumor showed intraepithelial growth within the small bronchi; this could represent either the in-situ phase of the tumor or pagetoid spread into the bronchial epithelium. The neoplastic cells of all patients harbored Epstein-Barr virus (EBV) as demonstrated by in situ hybridization for EBV-encoded small nuclear RNAs. All eight Asian patients with pulmonary LELC previously reported in the literature similarly have been EBV-positive, whereas the four reported Caucasian patients all have been EBV-negative. Lymphoepithelioma-like carcinoma of lung occurring in Asians is an EBV-associated neoplasm; it also appears to occur at a higher frequency in Asians than Caucasians. It usually presents as a solitary subpleural nodule, and there is no strong association with cigarette smoking. Most patients have early stage disease at presentation. From the limited available data, the behavior of LELC of lung is highly variable, ranging from apparent curability by excision (particularly for localized disease) to highly aggressive, extensive disease at presentation.Cancer 09/1995; 76(3):413-22. · 4.77 Impact Factor -
Article: Detection of Epstein-Barr virus only in lymphoepithelial carcinomas among primary carcinomas of the lung.
Histopathology 07/1995; 26(6):576-8. · 3.08 Impact Factor -
Article: Detection of Epstein-Barr virus in Hodgkin's disease occurring in an Oriental population.
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ABSTRACT: Like Burkitt's lymphoma, the strength of association of Epstein-Barr virus (EBV) with Hodgkin's disease occurring in different populations and clinical settings is highly variable, being 30% to 50% in Western countries, nearly 100% in Third World countries like Peru and Honduras, and nearly 100% in patients seropositive for human immunodeficiency virus. Data on the Oriental populations are very limited. Therefore, the current study was performed on the Chinese population of Hong Kong, where the incidence of Hodgkin's disease is low and EBV seroconversion occurs early in life. Twenty-three consecutive samples of Hodgkin's disease collected from 18 male and five female patients over a 12-year period were studied. The first age peak occurred in the second decade of life, and the second peak in the seventh decade. Using the sensitive and specific EBV-encoded RNAs (EBERs) in situ localization technique, positive labeling of the Reed-Sternberg cells and their variants was detected in five of five samples (100%) of mixed cellularity, nine of 16 samples (56%) of nodular sclerosing, one of one sample (100%) of lymphocyte depleted, and none of one sample (0%) of nodular lymphocyte predominant Hodgkin's disease. Further analysis of the data by age group yielded the following results: four of five (80%) for age younger than 15 years, three of nine (33%) for age 15 to 49, and eight of nine (89%) for age 50 or higher, confirming the reported strong association of EBV with Hodgkin's disease at the extremes of life. The overall positivity rate was 65%, which was intermediate between that reported in the Western populations and that in the Third World countries. These findings can be explained by the epidemiological pattern of Hodgkin's disease in Hong Kong, in which the first age peak is left-shifted to a younger age compared with that of Western populations (but not as early as that observed in Third World countries), moving the peak toward an age bracket in which Hodgkin's disease shows stronger association with EBV.Human Pathlogy 04/1995; 26(3):314-8. · 2.88 Impact Factor -
Article: A possible prognostic role of immunoglobulin-G antibody against recombinant Epstein-Barr virus BZLF-1 transactivator protein ZEBRA in patients with nasopharyngeal carcinoma.
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ABSTRACT: Epstein-Barr virus BZLF-1 replication activator (ZEBRA) is involved in the switch from viral latency to a productive cycle. Previous immunofluorescent study has shown that patients with nasopharyngeal carcinoma (NPC) have elevated immunoglobulin-G (IgG) antibody titres against recombinant ZEBRA protein (ZEBRA/IgG). The prognostic role of ZEBRA/IgG was further investigated by enzyme-linked immunosorbent assay (ELISA) in 110 NPC patients under long period of clinical follow-up. Ninety-seven percent (85 of 88) of the patients with NPC had significantly higher ZEBRA/IgG titres (geometrical mean titre, i.e., GMT = 8397) than normal Chinese individuals (GMT = 233 and P < 0.0001). Based on Kaplan-Meier analysis, the actuarial survival in patients with high ZEBRA/IgG titres (25%) after radiotherapy was significantly lower than that of those with low (76%; P = 0.0008) or intermediate titres (62%; P = 0.0036), although the titres taken before treatment did not bear such a relationship. Subdividing the patients into either individual UICC or Ho's stages, those with late-stage disease (UICC Stage 4 and Ho's Stages 3 and 4) and with high ZEBRA/IgG titres also had poorer prognosis than those with disease of the same stages but who had low titres. Poor prognosis in those with high titres could be associated with a high risk of distant metastasis because consistent titre increase was found in the majority of patients who later developed distant metastasis either in the lung or liver. Only a minimal increase was found in patients with recurrence in the cervical lymph nodes. No consistent increase was observed, however, in patients whose disease was in remission or the majority of those with bone metastasis or local recurrence in the nasopharynx. The postradiotherapy ZEBRA/IgG titre could be a potentially useful marker for differentiating NPC patients with poor prognosis from those at high risk for the development of distant metastasis to the lung or liver.Cancer 12/1994; 74(9):2414-24. · 4.77 Impact Factor -
Article: Specific association of Epstein-Barr virus with lymphoepithelial carcinoma among tumors and tumorlike lesions of the salivary gland.
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ABSTRACT: The Epstein-Barr virus (EBV)-encoded RNAs in situ localization procedure is a convenient, highly sensitive, and highly specific technique that is applicable to routinely fixed, paraffin-embedded tissue sections; this technique can be used for the study of the association and, hence, the possible causal role of EBV in tumors. This study was performed to elucidate whether EBV plays a role in the pathogenesis of tumors that arise in the salivary glands, since the salivary gland is known to be a reservoir for EBV replication. Cases that were selected included 61 examples of various benign and malignant neoplasms, as well as tumorlike conditions of the major and minor salivary glands. Only the five cases of lymphoepithelial carcinoma (so-called malignant lymphoepithelial lesion) and the single case of metastatic nasopharyngeal undifferentiated carcinoma showed staining with EBV-encoded RNAs, whereas negative findings were found in all of the other cases. In the cases with positive results, all of the neoplastic epithelial cells showed strong nuclear signals, but the lymphoid cells were negative. The consistent association of EBV with lymphoepithelial carcinoma of the salivary gland suggests that the virus probably plays a causal role in this tumor, at least in the Asian population, whereas there is no evidence for a causal role of EBV in other primary tumors of the salivary gland.Archives of pathology & laboratory medicine 11/1994; 118(10):994-7. · 2.58 Impact Factor -
Article: Detection of Epstein-Barr viral RNA in malignant lymphomas of the upper aerodigestive tract.
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ABSTRACT: Recent studies have suggested a probable etiologic association between Epstein-Barr virus (EBV) and nasal lymphomas, irrespective of geographic location. This study was performed to investigate the strength of association of EBV with non-Hodgkin's lymphomas of the upper aerodigestive tract, based on a large series of cases that have been thoroughly immunophenotyped on frozen tissues. A sensitive in situ hybridization technique was used to detect EBV encoded RNA (EBER) in paraffin sections. Among 30 cases of nasal/nasopharyngeal T-cell lymphoma, 25 (83.3%) were EBER-positive. In the positive cases, most of the neoplastic cells showed strong nuclear signals. Further analysis of this group of tumors showed that all 21 cases (100%) with a CD56+ CD3-phenotype were EBER positive, whereas four of nine cases (44.4%) with a CD56-negative immunophenotype were positive. Only one of 10 cases (10%) of nasal/nasopharyngeal B-cell lymphoma was EBER positive; the positive case was a diffuse mixed-cell lymphoma and could not be distinguished morphologically from the negative cases. Among the 21 cases of lymphoma of the tonsils and back of the tongue (20 B-lineage and one T-lineage), none was EBER positive. In the normal mucosa of the nose/nasopharynx or tonsil (20 cases studied), only very rare EBER-positive small lymphocytes were found in two cases. The almost exclusive detection of EBER in nasal/nasopharyngeal T-cell neoplasms among the lymphomas of the upper aerodigestive tract suggests that EBV probably plays an etiologic role in the pathogenesis of this group of tumors and is not simply a passenger virus, and neither is this merely a site-dependent phenomenon in view of the weak association with nasal/nasopharyngeal B-cell lymphoma.American Journal of Surgical Pathology 10/1994; 18(9):938-46. · 4.35 Impact Factor -
Article: The Rosai-Dorfman disease histiocytes are not infected by Epstein-Barr virus.
Histopathology 08/1994; 25(1):88-90. · 3.08 Impact Factor -
Article: In situ localization of Epstein-Barr virus encoded RNA in non-nasal/nasopharyngeal CD56-positive and CD56-negative T-cell lymphomas.
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ABSTRACT: We recently reported a group of non-nasal/nasopharyngeal hematolymphoid malignancies expressing the natural killer cell marker CD56, characterized by frequent extranodal localization, angiocentricity, and aggressive clinical course (HUM PATHOL 23:798-804, 1992). Because we have shown a very strong association of Epstein-Barr virus (EBV) with CD56-positive T-cell lymphomas of the nose nasopharynx, we asked whether a similar association also occurs with the non-nasal CD56-positive T-cell lymphomas. In situ localization of EBV encoded RNA (EBER) was performed on paraffin sections of 15 such cases, including the nine previously reported cases and six new cases (three showing prominent hepatosplenic involvement and three showing involvement of one or more extranodal sites, such as the parotid gland, tonsils, gastrointestinal tract, skeletal muscle, and testis). A case was considered positive when the majority of the tumor cells showed nuclear signal. Ten cases showed EBER positivity, and all but one of them were negative for CD3 and other T-cell markers, except CD2. Only one of four cases showing a CD3-positive phenotype was EBER positive. Of the remaining two CD3-negative EBER-negative cases, one showed a histiocytic phenotype and the other was positive for multiple T-cell markers. Among 15 cases of CD56-negative non-nasal peripheral T-cell lymphoma studied for comparison, six were CD3-negative, among which three showed EBER positivity. All nine CD3-positive cases were EBER negative. Five cases (three CD3 positive and two CD3 negative) showed rare isolated (< 1%) EBER-positive tumor cells. We conclude that among non-nasal T-cell lymphomas, EBV is strongly correlated with CD56 positivity (66.7% v 20%), and the positive cases almost always show an immunophenotype identical to that commonly observed in nasal lymphomas (CD2 positive, CD3 negative, and CD56 positive). Thus, EBV may play an etiologic role in these CD56-positive lymphomas. There is also a correlation between EBER positivity and CD3 negativity, irrespective of the CD56 status. The presence of isolated EBER-positive cells in CD56-negative T-cell lymphomas, occurring at a frequency similar to that reported in the European population, probably represents secondary infection of tumor cells.Human Pathlogy 08/1994; 25(8):758-65. · 2.88 Impact Factor
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1995–1999
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Queen Elizabeth Hospital
Hong Kong, Hong Kong
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