[show abstract][hide abstract] ABSTRACT: This paper describes a fatal case of culture-confirmed, community-associated methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in an 8-month-old child in Hong Kong in 2001. Stored cytological materials prepared from the pleural fluid were retrieved for molecular analysis. The result indicates the presence of a Panton-Valentine leucocidin-positive, spa type 019 MRSA.
Journal of clinical microbiology 08/2008; 46(7):2457-8. · 4.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: The present study aimed to determine the alterations of antioxidant activities in erythrocytes from patients with nonsmall cell lung carcinoma (NSCLC). A comparative study of the systemic antioxidant activities in red blood cell lysate from subjects with NSCLC and healthy control subjects was conducted. The antioxidants catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured using chemical kinetic reactions under spectrophotometry. In total, 189 cases of mostly advanced-stage IIIB or stage IV NSCLC and 202 healthy controls were studied. In subjects with lung cancer, there was similar catalase activity, lower SOD activity (median (interquartile range) 13.4 (9.0-27.2) versus 48.7 (27.0-64.3) U x (ghaemoglobulin(Hb)(-1)), and higher GPx activity (175.2 (126.6-288.3) versus 49.2 (39.5-59.2) mU x (gHb)(-1)) compared with controls. The antioxidant activities in lung cancer subjects were not associated with age, sex, smoking status, or tumour cell types. However, more advanced disease (stage IV compared with stage IIIB) was associated with lower SOD activity. Using multivariable analysis, the presence of lung cancer independently predicted SOD and GPx activities. In conclusion, nonsmall cell lung carcinoma in Chinese subjects is associated with alterations in systemic antioxidant activities, which may play an important role in carcinogenesis.
European Respiratory Journal 03/2007; 29(2):273-8. · 6.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of this study was to evaluate the role of autofluorescence bronchoscopy (AFB) in the routine work-up of lung cancer. Consecutive patients with atypical or suspicious cells in sputum or bronchial aspirate, no localising abnormality on chest radiography and nondiagnostic white-light bronchoscopic (WLB) results were recruited. WLB and AFB were performed sequentially during the same session. All abnormal areas detected by WLB, AFB or both were sampled and the biopsy specimens sent for histological examination. Sixty-two patients were recruited within the 32-month study period. Seventeen had no endobronchial lesion detected. Among the 45 patients with endobronchial lesions, 37 had lesions with a histopathological grade of mild dysplasia or less; of the eight patients who had a lesion with a histological grade of moderate dysplasia or worse, five were found to have lung cancer, two invasive lung cancer and three an intra-epithelial neoplasm (severe dysplasia). Lesions showing moderate dysplasia or worse were more commonly found in patients with suspicious cells than in those with atypical cells on sputum examination. AFB was more sensitive than WLB (91 versus 58%) at detecting these lesions, but less specific (26 versus 50%). A combination of white-light and autofluorescence bronchoscopy can increase the diagnostic yield of this invasive procedure in patients exhibiting abnormal sputum cytology.
European Respiratory Journal 12/2006; 28(5):915-9. · 6.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: Lymphoepithelioma-like carcinoma of the lung (LELC) is a rare form of non-small cell lung cancer predominantly affecting young non-smoking Asians, and there has been only limited experience in its palliative chemotherapy and radiotherapy. We investigated tumour response, time to progression and survival of LELC patients who received such treatment.
We prospectively recruited patients with confirmed advanced LELC who were treated with chemoradiotherapy in our unit, a regional tertiary referral centre for lung cancer treatment.
There were 10 patients (five males, age 47 +/- 9.8 years, median follow-up 22 months) with advanced LELC (respectively 1, 4, and 5 patients at TNM stage IIIA, IIIB and IV) who received systemic chemotherapy and radiotherapy. The primary chemotherapy regimen consisted of 5-fluorouracil/leucovorin/cisplatin. The response rates to 5-fluorouracil/leucovorin/cisplatin were 60% partial response, 10% stable disease, and 30% progressive disease. Eight patients were also given local radiotherapy. Five patients received salvage chemotherapy when disease progressed after primary chemotherapy. The overall median survival was 23.4 +/- 4.7 months.
The encouraging response to combination chemotherapy with 5-fluorouracil/leucovorin/ cisplatin, although empirical, supports its use with radiotherapy in unresectable lymphoepithelioma-like carcinoma of the lung.
The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 08/2004; 8(7):890-5. · 2.61 Impact Factor
[show abstract][hide abstract] ABSTRACT: Silicosis is an important form of pneumoconiosis, which is caused by significant exposure to crystalline silica. The carcinogenicity of silica, despite traditional beliefs, in relation to lung cancer has been controversial. Lymphoepithelioma-like carcinoma of the lung, an Epstein-Barr virus-associated undifferentiated carcinoma, is a rare entity of pulmonary malignancy, which tends to affect young nonsmoking Asians. The first case of silicosis, initially complicated by pulmonary tuberculosis, which later developed into advanced lymphoepithelioma-like carcinoma of the lung is reported. A combination of 5-fluorouracil, cisplatin and calcium folinate resulted in partial tumour response.
European Respiratory Journal 09/2003; 22(2):383-6. · 6.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: Our objectives were to document CT features of advanced primary pulmonary lymphoepithelioma-like carcinoma (LELC) and to determine features that may assist differentiation from other non-small cell lung cancers (NSCLC). Imaging and clinical data of all patients with biopsy-proven pulmonary LELC ( n=12) were retrieved from a database of all NSCLC patients over a 2-year period. Twenty-five controls were recruited from other inoperable non-LELC NSCLC patients from the database. Pre-treatment CT scans of the thorax of both study and control patients were reviewed for lobe involved; tumour site, borders and size; and pleural, vascular or pulmonary involvement. Presence of lymphangitis carcinomatosis was noted. Lymph node metastasis was characterised as ipsilateral or contralateral enlarged (>1 cm) mediastinal or hilar nodes, or as peribronchovascular nodal spread. Differences between the two groups were tested using Mann-Whitney rank-sum test. The LELC tumours were significantly larger (45.67 vs 17.71 cm(2)) than controls and were closely associated with the mediastinum. There were more LELC tumours with well-defined borders ( p<0.001) and fewer with spiculated borders ( p<0001) than non-LELC tumours. There was increased peribronchovascular nodal spread ( p=0.01) and vascular encasement ( p=0.02) in LELC compared with non-LELC tumours. Advanced primary pulmonary LELC has distinct radiological features, and can appear as well-defined tumour closely associated with the mediastinum, with peribronchovascular spread and vascular encasement.
European Radiology 03/2003; 13(3):522-6. · 3.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: Pulmonary cryptococcosis is a very rare form of pneumonia, which is seldom seen among immunocompetent patients. We report the case of a 36-year-old man who presented with indolent pneumonia that was subsequently diagnosed to be pulmonary cryptococcosis without other systemic involvement. Contrary to formal belief, there was evidence of residual lung fibrosis 12 months after initial presentation. The features of pulmonary cryptococcosis reported in the Asian Pacific region are also reviewed.
[show abstract][hide abstract] ABSTRACT: To establish an updated clinical profile of adenocarcinoma of the lung.
Retrospective review of clinical charts, chest radiography, and computed tomography of consecutive patients who attended Queen Mary Hospital in Hong Kong between June 1995 and December 1997.
In the 115 patients studied, 13% were <40 years of age (33.3% ever smokers). Haemoptysis is more common among patients with early disease, while finger clubbing was detected more commonly among smokers and ex-smokers. Most (98.3%) patients had abnormal chest radiology including presence of mass lesion, pleural effusion, collapse/consolidation, and effusion. Patients with adenocarcinoma were significantly more likely to be younger, female, in advanced disease (stage IIIB and IV), non-smoker, and symptomatic on presentation (p<0.05) than those with squamous cell lung cancer (n=128).
The clinical profile of Chinese adenocarcinoma patients should help clinicians in the diagnosis and management of these patients.
Postgraduate Medical Journal 12/2001; 77(913):708-12. · 1.61 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim was to study the yield of malignant or suspicious cells from bronchoalveolar lavage (BAL), endobronchial biopsy (BX) and endobronchial brushing (BR) specimens obtained at bronchoscopy.
We prospectively followed up all patients who had undergone bronchoscopy and studied those with subsequent diagnosis of bronchial carcinoma at a tertiary referral centre. Bronchoalveolar lavage, BX and BR were performed, sequentially whenever possible, by one pulmonologist. The parameters assessed were age, gender, macroscopic bronchoscopic findings, TNM staging, radiological findings, histological typing, and diagnostic yield from BAL, BX, and BR.
One hundred patients (31 females, 69 males; mean age +/- SD, 61.8+/-12.7 years; range 32-81 years) were studied between 1995 and 1997. Of these, BAL, BX and BR were performed on 100, 64 and 37 cases which yielded diagnostic specimens for bronchial carcinoma in 69, 78.1, and 62.2% of cases, respectively (P > 0.05). Diagnostic specimens were therefore obtained in 69,50, and 23% of the entire patient cohort from BAL, BX, and BR, respectively (P < 0.001). The diagnostic yield of BAL was independent of patient age, gender, site of lesion, TNM staging, histological typing and macroscopic bronchoscopic findings. Addition of BX, BR and postbronchoscopic sputum sampling to BAL only increased the yield of diagnostic specimens for bronchial carcinoma by 7, 0, and 4%, respectively.
Bronchoalveolar lavage is a highly effective sampling method to obtain cytological evidence for bronchial carcinoma. The diagnostic yield for BAL is independent of tumour or other clinical characteristics. Further studies should be performed to confirm these important and clinically relevant findings.
[show abstract][hide abstract] ABSTRACT: The successful establishment of angiogenesis depends on a complex process of endothelial proliferation and organization. The angiopoietins (Ang-1 and Ang-2) and Tie2 ligand-receptor system is essential for the regulation of vascular maturation and stability during embryonic development. Together with the vascular endothelial growth factor (VEGF)-mediated pathway, they have been implicated in the control of normal physiological angiogenesis. We investigated their potential role and interaction in the development of lung cancers by comparing the expression pattern and inter-relationship of Ang-1 and 2, Tie2 and VEGF levels in 28 pairs of primary non-small cell lung cancers (NSCLC) and normal lung. Using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and in-situ hybridization (ISH), we showed that in NSCLC, there was significantly up-regulated VEGF expression by the tumour cells and an increased intensity of Ang-2 expression in the tumour vessels. The number of Ang-2-expressing vessels also correlated with the grades of tumour cell expression of VEGF. On the other hand, normal lung expressed constitutively high and correlated levels of Ang-1 and Tie2, which were significantly reduced in the carcinomas. The findings suggested a role of the Ang-1/Tie2 pathway in the maintenance of the complex vasculature in normal lung, while collaborative activities between the Ang-2 and VEGF pathways might be important in promoting tumour angiogenesis in NSCLC.
Lung Cancer 08/2000; 29(1):11-22. · 3.39 Impact Factor
[show abstract][hide abstract] ABSTRACT: Angiogenesis is an essential requirement for the development, progression and metastasis of malignant tumours. Studies on transgenic mouse models have shown that angiogenesis begins in the pre-malignant phase of oncogenesis, when dysplastic lesions acquire an increased microvasculature. To investigate the relationship between the expression of vascular endothelial growth factor (VEGF) and colorectal tumour progression, we have studied VEGF expression level and splice variant pattern by semi-quantitative RT-PCR and the cellular source of VEGF expression by in situ hybrization (ISH) in a range of lesions that modelled the tumour-development pathway from normal colon to invasive colorectal adenocarcinomas. Colonic adenomas showed a statistically significant up-regulation of VEGF expression over normal tissues, with a further increase during the development of adenocarcinomas. Tumour cells formed the major source of VEGF expression, with a minor contribution from mononuclear cells in the tumour stroma and enhanced expression in tumour cells around necrotic regions. The comparable expression level in both the in situ and invasive components in the same tumours indicated that a high VEGF expression capacity had been acquired prior to establishment of the invasive phenotype. Our findings support activation of VEGF as the molecular basis for the discrete induction of angiogenesis in the pre-malignant phase of colorectal tumour development.
International Journal of Cancer 07/1999; 81(6):845-50. · 6.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: Microsatellite instability (MI), the phenotypic manifestation of mismatch repair failure, is found in a proportion of gastric carcinomas. Little is known of the links between MI and Epstein-Barr virus (EBV) status and clinicopathological elements. Examination of genes mutated through the MI mechanism could also be expected to reveal important information on the carcinogenic pathway. Seventy-nine gastric carcinomas (61 EBV negative, 18 EBV positive) from local Hong Kong Chinese population, an intermediate-incidence area, were examined. Eight microsatellite loci, inclusive of the A10 tract of type II transforming growth factor beta receptor (TbetaR-II), were used to evaluate the MI status. MI in the BAX and insulin-like growth factor II receptor (IGF-IIR) genes were also examined. High-level MI (>40% unstable loci) was detected in ten cases (12.7%) and low-level MI (1-40% unstable loci) in three (3.8%). High-level MI was detected in two EBV-associated cases (11%) and the incidence was similar for the EBV-negative cases (13%). The high-level MIs were significantly associated with intestinal-type tumours (P = 0.03) and a more prominent lymphoid infiltrate (P = 0.04). Similar associations were noted in the EBV-positive carcinomas. The high-level MIs were more commonly located in the antrum, whereas the EBV-associated carcinomas were mostly located in body. Thirteen cardia cases were negative for both high-level MI and EBV. All patients aged below 55 were MI negative (P = 0.049). Of the high-level MIs, 80% had mutation in TbetaR-II, 40% in BAX and 0% in IGF-IIR. Of low-level MIs, 33% also had TbetaR-II mutation. These mutations were absent in the MI-negative cases. Of three lymphoepithelioma-like carcinomas, two cases were EBV positive and MI negative, one case was EBV negative but with high-level MI. In conclusion, high-level MIs were present regardless of the EBV status, and were found in a particular clinicopathological subset of gastric carcinoma patient. Inactivation of important growth regulatory genes observed in these carcinomas confirms the importance of MI in carcinogenesis.
British Journal of Cancer 03/1999; 79(3-4):582-8. · 5.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Lymphoepithelioma-like carcinoma (LELC) of the lung is a recently recognized primary non-small cell lung carcinoma with distinct clinicopathological features and an aetiological association with Epstein-Barr virus (EBV) infection. The tumour consists of clusters and sheets of poorly or undifferentiated tumour cells in close association with numerous mononuclear inflammatory cells, including a rich component of tumour-associated macrophages (TAMs). To investigate the molecular mechanism leading to the TAM-rich stroma, the expression of a monocyte-specific chemotactic and activating factor, monocyte chemoattractant protein-1 (MCP-1), was studied by reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization (ISH), and the presence of TAMs was demonstrated by immunohistochemistry in nine LELCs. The results were compared with those found in 17 conventional non-small cell lung carcinomas. RT-PCR showed specific MCP-1 amplification in both LELCs and non-LELCs, but ISH demonstrated a unique and extensive expression of MCP-1 transcripts by the tumour cells of LELCs only, while TAMs, stromal fibroblasts, and endothelial cells formed the major source of MCP-1 in non-LELCs. TAMs in LELCs were more abundant and showed a close topographical relationship with the MCP-1-expressing tumour cells. The results indicate that tumour cell expression of MCP-1 in LELCs is an important mechanism contributing to their distinctive morphological features. This is the first study that demonstrates the in vivo upregulation of a monocyte-specific chemokine by EBV-related carcinomas, illustrating an interesting aspect of tumour biology in EBV-related neoplasms.
The Journal of Pathology 01/1999; 186(4):372-7. · 7.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: Vascular endothelial growth factor (VEGF) is a hypoxia inducible angiogenic and vascular permeability factor. Although VEGF expression in glioblastoma is induced by hypoxia, its expression in renal cell carcinoma and hemangioblastoma is thought to be related to mutation of the von Hippel-Lindau (VHL) gene. It is not certain whether other lesions in VHL syndrome are associated with an elevated VEGF level. We report a VHL syndrome patient with multiple hemangioblastomas and bilateral epididymal clear cell papillary cystadenomas. In situ hybridization revealed high levels of VEGF mRNA in the clear cells of the epididymal tumor and the stromal cells of the hemangioblastoma. This lends support to the notion that upregulation of VEGF is caused by loss of the wild-type VHL protein. We postulate that the elevated VEGF levels may account for the cyst formation and vascularized stroma present in these VHL-associated tumors.
Human Pathlogy 12/1998; 29(11):1322-4. · 2.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: Angiogenesis, a prerequisite for tumor growth and progression, results from a shift in the equilibrium between angiogenic factors and angiogenic inhibitors. Vascular endothelial growth factor (VEGF) has been identified as one of the most important factors mediating angiogenesis in physiological and pathological conditions. Through alternative splicing, four isoforms of VEGF are formed, consisting of 206, 189, 165, and 121 amino acids, respectively. VEGF206 and VEGF189 differ from VEGF165 and VEGF121 in their bioavailability, with the longer forms being matrix-bound and the shorter forms freely diffusible. To investigate the relative importance of the VEGF isoforms in neoplastic transformation, we studied the pattern of splice variant expression by reverse transcription polymerase chain reaction (RT-PCR) in 18 lung and 11 colonic carcinomas and their corresponding normal tissues, respectively. The findings showed a significant upregulation of VEGF in both carcinomas, with VEGF165 and VEGF121 being the predominant forms; VEGF189 was significantly expressed in normal lung but not colon; and VEGF206 was not detected in any specimen. The findings indicate that during malignant progression, an angiogenic switch favoring the shorter diffusible isoforms is likely to confer on the tumor a growth advantage. From the differential expression of VEGF isoforms in normal lung and colonic tissues, different functional roles of the splice variants is suggested. In particular, VEGF189 may be important for the maintenance of the vascular integrity of the lung.
Human Pathlogy 10/1998; 29(9):910-4. · 2.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenic factor, which is known to be upregulated in most cases of glioblastoma multiforme (GBM). The expression of VEGF and its receptors in ependymomas, oligodendrogliomas, and particularly the expression during anaplastic progression of these three types of gliomas has not been studied extensively. Fifty-six gliomas, consisting of 10 ependymomas, 12 oligodendrogliomas, 3 anaplastic oligodendrogliomas, 6 astrocytomas grade II, 5 anaplastic astrocytomas, and 20 glioblastoma multiformes, were investigated for VEGF and receptor expression using in situ hybridization (ISH) and reverse transcription polymerase chain reaction (RT-PCR). Results showed that VEGF was moderately to strongly expressed in 8 of 10 ependymomas and in all anaplastic oligodendrogliomas and glioblastoma multiforme cases. These tumors displayed similar degrees of extensive necrosis and vascular proliferation, with VEGF expression consistently seen in tumor cells around necrotic areas. The VEGF expression, although present at a lower level, also was shown in 4 of 12 oligodendrogliomas, in 3 of 6 astrocytomas grade II, and in 2 of 5 anaplastic astrocytomas, with a regional rather than diffuse pattern of positive result. The findings from the in situ hybridization study correlated with the expression index, as determined by reverse transcription polymerase chain reaction. Expression of VEGF was correlated significantly with vascular proliferation (p < 10(-5)) and necrosis (p < 10(-5)), as well as with microvessel density (p = 0.002, rs = 0.41). The VEGF receptors, kinase domain region (KDR) and Fms-like-tyrosine kinase (Flt-1), also were upregulated in the tumor vasculature of glioblastoma multiforme, anaplastic oligodendrogliomas, and ependymomas with necrosis, whereas the astrocytomas grade II, anaplastic astrocytomas, and oligodendroglioma tumors tended to express a weak to nondetectable signal. Anaplastic progression in all three types of gliomas is heralded by the occurrence of small zones of VEGF-expressing cells and early vascular proliferation, followed by an accelerated phase of angiogenesis closely associated with VEGF induction around areas of necrosis and with the expression of VEGF receptors in the tumor vasculature.
American Journal of Surgical Pathology 08/1998; 22(7):816-26. · 4.87 Impact Factor
[show abstract][hide abstract] ABSTRACT: The objective of this study was to evaluate the clinical, radiological investigation profiles, and ciliary function and ultrastructure in Chinese patients with Kartagener's syndrome (presence of dextrocardia, sinusitis and bronchiectasis). All patients with dextrocardia were assessed for the presence of sinusitis and bronchiectasis in our hospital network. Patients identified with Kartagener's were assessed when they were at steady state for their bronchiectasis. Seven cases (4 males; mean age 34.9 years) were identified and systematically reviewed. The mean 24 h sputum volume was 26.6 +/- 32.77 mL/day and the patients suffered from a mean of 2.9 exacerbations/year. Nasal symptoms (anosmia in one, obstruction in six and persistent discharge in three patients) were common. Only two cases (1 M) were married and both had normal fertility. Lung function assessment showed a mean FEV1/FVC of 83.3 +/- 38.78/86.5 +/- 36.72 (% predicted) with little reversibility. High resolution computerized tomography (HRCT) revealed bronchiectactic involvement of the lower lobes in seven and middle lobe/lingula in four cases. Assessment of alpha-1-anti-trypsin, aspergillus precipitins, auto-antibodies and serology for Pseudomonas pseudomallei was normal. Sputum culture yielded Pseudomonas aeruginosa in three, Haemophilus influenzae in three and commensals in one case. Phase contrast microscopy assessment of respiratory cilia, obtained by brushing the inferior turbinate, revealed that most of the mucosa was unciliated. The mean ciliary beat frequency was 5.2 +/- 6.76 Hz (range 0-13.7; normal range 12-18 Hz). Four patients had immotile cilia whilst the rest had normal ciliary movement. Transmission electron microscopy showed the absence of dynein arms in four patients. The results of this study show that patients with Kartagener's syndrome may have normal ciliary ultrastructure and the absence of dynein arms is not necessarily associated with ciliary immotility. The presence of ciliary immotility might have prognostic value as these patients appear to have more active bronchiectasis. Our experience on this series should help clinicians in the investigation and management of these patients.
[show abstract][hide abstract] ABSTRACT: The presence of lysozyme protein in some gastric adenomas and adenocarcinomas has been well documented. There have been relatively few studies investigating the presence of lysozyme in tumours of the large intestine and they show contrasting results. We aim to investigate the cellular source and expression of lysozyme in colonic adenomas and adenocarcinomas.
We randomly selected 29 and 27 colonic adenomas and adenocarcinomas, respectively. Using in-situ hybridization (ISH) and immunohistochemistry (IHC), we found an up-regulation of lysozyme in the dysplastic epithelium of all the adenomas studied, with more than 80% of cases expressing moderate to strong signals. Although the up-regulation of lysozyme was also observed in adenocarcinomas, only 30% of the cases showed moderate to strong signals, mostly with an uneven distribution. Down-regulation of lysozyme in the severely dysplastic and invasive foci were noted in some cases of adenoma with malignant transformation. Normal colonic glands were consistently negative for lysozyme at both the mRNA and the protein level, but inflamed and immature regenerative colonic epithelium at the crypt base showed positive signals in a similar pattern to those observed in the dysplastic epithelium of the adenomas.
Our results confirm that colonic epithelium can produce lysozyme and its expression is up-regulated in the dysplastic epithelium in adenomas and in invasive cancer cells. It is interesting that regenerative colonic epithelium showed a similar pattern of lysozyme expression as in adenomas. The loss of lysozyme secreting phenotype in most of the invasive tumours suggests that lysozyme may not confer an advantage to tumour progression.
[show abstract][hide abstract] ABSTRACT: Previous studies suggest that the polymorphic p53 intron 2 displays a high frequency of mutations, occurring with different frequencies in tumor tissues versus peripheral blood of lung cancer patients as compared to healthy individuals. We evaluated the significance of these polymorphisms and mutations utilizing matched triple specimens from the lung tumor, normal lung tissue, and peripheral blood of cancer patients. Identical genotypes were observed in normal tissues and blood, while 4 mutations were observed in tumors. The A1 allelic frequency was increased in the adenocarcinoma tissues as compared to normal tissues. Two p53 exon 2 polymorphisms were detected, appearing with equal frequencies among cancer patients and healthy individuals. The p53 intron 2 polymorphic locus is a hot spot for mutations in Hong Kong lung cancer patients.
[show abstract][hide abstract] ABSTRACT: Vascular endothelial growth factor (VEGF), a potent angiogenic and vascular permeability factor, is important in the angiogenesis of glioblastoma. A major difference between pilocytic astrocytoma, a grade I tumor, and the grade II fibrillary astrocytoma is the vascular proliferation, highly vascularized stroma, and great propensity for cyst formation in the former. In order to explore factors regulating such angiogenesis and cyst formation in pilocytic astrocytoma, we examined expression of VEGF and its receptors (KDR and Flt-1) using in situ hybridization. In all 14 cases a high level of VEGF transcripts could be demonstrated. These were found in specific regions, namely, in the tumor cyst wall, in areas of hyaline cystic degeneration, in stellate reticulated astrocytes around microcysts in the biphasic compact and loose areas, and in tumor cells with degenerative pleomorphic multicoated nuclei. KDR and Flt-1 were expressed in the tumor vasculature, with particularly high levels seen in coiled young proliferating vessels, especially those in the cyst wall. Given the known angiogenic and vascular permeability activities of VEGF, we propose that VEGF plays an important role in molding the characteristic morphologic features of this tumor, namely, the formation of cysts, microcystic pattern, hyaline cystic degeneration, hyaline vessels, and vascular proliferation. Mechanisms that block the VEGF pathway could constitute a potential therapeutic strategy for the treatment of this tumor.
American Journal of Surgical Pathology 09/1997; 21(8):941-50. · 4.87 Impact Factor