An Improved Quantum-Behaved Particle Swarm Optimization Algorithm with Elitist Breeding for Unconstrained Optimization.

An improved quantum-behaved particle swarm optimization with elitist breeding (EB-QPSO) for unconstrained optimization is presented and empirically studied in this paper. In EB-QPSO, the novel elitist breeding strategy acts on the elitists of the swarm to escape from the likely local optima and guide the swarm to perform more efficient search. During the iterative optimization process of EB-QPSO, when criteria met, the personal best of each particle and the global best of the swarm are used to generate new diverse individuals through the transposon operators. The new generated individuals with better fitness are selected to be the new personal best particles and global best particle to guide the swarm for further solution exploration. A comprehensive simulation study is conducted on a set of twelve benchmark functions. Compared with five state-of-the-art quantum-behaved particle swarm optimization algorithms, the proposed EB-QPSO performs more competitively in all of the benchmark functions in terms of better global search capability and faster convergence rate.

[Differentially expressed genes between upward and downward progressing types of nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Upward (local growth and invasion of the base of skull), downward (distant metastasis) and mixed progressing types of nasopharygeal carcinoma (NPC) have been observed when the disease progress to middle-late stage. The upward and downward progressing types are evidently different in clinical symptom, therapy strategy and prognosis. Identification of the molecular differences between them is very important for molecular classification, prognostic prediction and research on neoplasia and development of NPC. This study was to discover the genes differentially expressed in upward and downward progressing types of NPC. METHODS: An oligo gene chip containing 21 300 genes was used to detect the genes differentially expressed between upward and downward progressing types of NPC. One of the differentially expressed genes detected was analyzed by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Seventeen genes were differentially expressed between upward and downward progressing types of NPC. The expression of SELB, Clorf29, GLE1L and FLJ20989 genes were up-regulated and the expression of 1D12A, ASPN, DCN, PRO2219, LRDD, DIO2, ULBP2, PRO3073, IGVH3, IGVH4, IGLJ3, PRO0943 and AK057247 genes were down-regulated in the upward progressing type as compared with those in the downward progressing type. The difference of gene expression was ranged from 2.30 to 4.23 folds. The high expression rate of DIO2 gene was significantly higher in downward progressing type than in upward progressing type (90.0% vs. 33.3%, P = 0.020). CONCLUSIONS: The gene expression patterns are significantly different between upward and downward progressing types of NPC. The expression of DIO2 gene is higher in the downward progressing type than in upward progressing type, which may be closely related to the metastasis potential of NPC.

[Correlations of biomolecular markers, such as P53 protein and vascular endothelial growth factor, to radiosensitivity of nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: About 20%-40% nasopharyngeal carcinoma (NPC) patients, who are in the same staging group, receiving the same treatment modality and radiotherapy dose, relapse in the irradiated fields within 5 years. This is mainly due to the differences in internal radiosensitivity. This study was to analyze the proliferation, apoptosis, angiogenesis, and lymphogenesis of tumor cells, and to explore the correlation of these factors to radiosensitivity. METHODS: P53 protein, vascular endothelial growth factor (VEGF) protein, survivin protein, VEGF-C protein, Ki67 protein, and microvascular density (MVD) of 60 biopsy samples from radiosensitive group and 60 from radio-resistant group were detected by immunohistochemistry, respectively. Their correlations to clinical characteristics were analyzed. RESULTS: The positive rates of P53, VEGF, survivin, VEGF-C, Ki67 were 65.0%, 57.5%, 60.8%, 42.5%, 57.5%, respectively. The positive rates of P53 and VEGF, and MVD in the radio-sensitive group and in the radio-resistant group were (25.97+/-21.26)%, (18.50+/-19.86)%, 32.65+/-19.61 and (37.85+/-28.67)%, (30.83+/-23.94)%, 41.95+/-16.97, respectively (P<0.05). The positive rates of Survivin, VEGF-C, and Ki67 between the two groups had no statistic difference (P>0.05). The correlations between P53, VEGF, and MVD were obvious. CONCLUSION: P53 protein, VEGF protein and MVD might be biomolecular markers for evaluating the internal radiosensitivity of NPC patients.

Improvement of survival after addition of induction chemotherapy to radiotherapy in patients with early-stage nasopharyngeal carcinoma: Subgroup analysis of two Phase III trials.

PURPOSE: Induction chemotherapy has not been shown to improve survival in nasopharyngeal carcinoma (NPC) in Phase III trials. To evaluate the effect of induction chemotherapy in NPC further, we performed subgroup analysis of two Phase III trials according to the T and N stage. METHODS AND MATERIALS: Data from two phase III trials comparing cisplatin/epirubicin or cisplatin/bleomycin/5-fluorouracil followed by radiotherapy (RT) vs. RT alone in NPC were pooled together for analysis. Patients were stratified into four subgroups according to the 1997 American Joint Committee on Cancer T and N stage: T1-T2N0-N1, Group 1 (early-stage disease); T1-T2N2-N3, Group 2 (advanced N disease); T3-T4N0-N1, Group 3 (advanced T stage); and T3-T4N2-N3, Group 4 (advanced T and N disease). Group 1 consisted entirely of patients with Stage IIB disease. A total of 784 patients were included for analysis on an intent-to-treat basis. The median follow-up for the surviving patients was 67 months. RESULTS: No significant differences in overall survival, locoregional failure-free, or distant metastasis-free rates were observed between the combined and RT arms in Groups 2 to 4. Significant differences in the overall survival and distant metastasis-free rates were observed only in Group 1, favoring the combined chemotherapy and RT arm. The 5-year overall survival rate was 79% in the combined arm and 67% in the RT-alone arm (p = 0.048). The corresponding 5-year distant metastasis-free rates were 86% and 74% (p = 0.0053). CONCLUSIONS: Our results have shown that patients in Group 1, with early-stage NPC treated by RT alone, had relatively poor survival because of distant metastases. The observation of improved outcomes in this subgroup after the addition of induction chemotherapy has not been previously reported and warrants additional investigation.

Elevated plasma big ET-1 is associated with distant failure in patients with advanced-stage nasopharyngeal carcinoma.

BACKGROUND: Endothelin-1 (ET-1) is a potent vasoactive peptide and a hypoxia-inducible angiogenic growth factor associated with the development and spread of solid tumors. The clinical significance of plasma big ET-1 in patients with advanced-stage nasopharyngeal carcinoma (NPC) is not known. METHODS: Pretreatment plasma big ET-1 levels were measured in 62 patients with advanced-stage NPC using a sandwich enzyme-linked immunoassay and compared with the levels from a control group (n = 19 participants). RESULTS: The median pretreatment plasma big ET-1 level in patients with advanced-stage NPC was 4.6 pg/mL (range, 1.9-15.2 pg/mL) and was significantly elevated compared with median plasma big ET-1 levels in healthy controls, 2.6 pg/mL (1.6-4.5 pg/mL) (P < .001). Using the upper limit (4.5 pg/mL) of control subjects as the cut-off value, plasma big ET-1 was < or = 4.5 pg/mL in 29 (46.8%) patients and > 4.5 pg/mL in 33 (53.2%) patients. A pretreatment plasma big ET-1 level > 4.5 pg/mL was associated with a significantly poorer 2-year distant metastasis-free survival rate (56.7% vs. 81.1%, P = .031). Multivariate analysis showed that N classification (hazard ratio [HR], 2.416; 95% confidence interval [CI], 1.071-5.447; P = .034) and pretreatment plasma big ET-1 level (HR, 3.151; 95% CI, 1.099-9.028, P = .033) were independent significant prognostic factors for posttreatment distant failure in patients with advanced-stage NPC. CONCLUSIONS: Pretreatment plasma big ET-1 levels may be useful in predicting posttreatment distant failure in patients with advanced-stage NPC.

[Clinical analysis of 1,142 hospitalized cantonese patients with nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Few large-scale epidemiologic investigations of nasopharyngeal carcinoma (NPC) at high incidence region in Guangdong province were reported in recent 20 years. This study was to summarize clinical data of a population of hospitalized Cantonese NPC patients,analyze the epidemiologic characteristics of NPC in the high incidence region, and provide references for the prevention and treatment of NPC. METHODS: Clinical data of 1 142 Cantonese NPC patients, hospitalized in Cancer Center of Sun Yat-sen University between Jan. 1998 and Aug. 2000, were collected according to well-designed forms and statistically analyzed. RESULTS: The morbidity of NPC in Cantonese showed obvious family clustering: 21.9% of the patients had family history of cancer, and 12.3% had family history of NPC. Moreover, the family clustering feature was more obvious in the population from the region with higher incidence of NPC. The positive rate of VCA/IgA antibody was 90.0%, and that of EA/IgA antibody was 74.5%; the titers were positively related to tumor burden. Early diagnostic rate of NPC was about 30%. CONCLUSIONS: NPC patients in Cantonese population have obvious family and territorial clustering. High positive rates of VCA/IgA and EA/IgA antibodies are helpful for early diagnosis of NPC.

[Impact of pre-radiotherapy hemoglobin level on local control of nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Oxygen increases tumor sensitivity to radiotherapy; tumor hypoxia is more prevalent in tumor patients with pretreatment hemoglobin concentration of < 130 g/L. This study was to evaluate impact of pre-radiotherapy hemoglobin level on radiotherapy outcome of nasopharyngeal carcinoma (NPC) patients. METHODS: Clinical and follow-up data of 166 NPC patients received definitive radiotherapy from 1999 to 2000 were reviewed. Pre-radiotherapy hemoglobin levels were stratified as high (> or =130 g/L) and low (< 130 g/L). Cox regression analysis was used to determine factors affecting local control. RESULTS: The median pre-radiotherapy hemoglobin level of the 166 patients was 135 (85-189) g/L. Hemoglobin was < 130 g/L in 68 (41%) patients, and > or =130 g/L in 98 (59%) patients. The pre-radiotherapy hemoglobin level of < 130 g/L was related to low 3-year local relapse-free survival rate (78% vs. 90%, P=0.015), but had no relations with distant metastasis-free survival (75% vs.77%, P=0.763) and overall survival rates (73% vs. 83%, P=0.056). Multivariate analysis showed that pre-radiotherapy hemoglobin level, T stage, and gender were independent prognostic factors for local failure. CONCLUSIONS: Pre-radiotherapy hemoglobin of < 130 g/L is a prognostic factor for local control of NPC. Strategies for maintaining pre-radiotherapy hemoglobin of > or =130 g/L before radiotherapy and during treatment should be further explored.

[Correlation of endothelin A receptor expression to prognosis of nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Endothelin A receptor (ET(A)R) activation contributes to tumor growth and metastasis, including cell proliferation, cell death, angiogenesis, and metastatic spread. In this study, we evaluated correlation of ET(A)R expression to clinical features of nasopharyngeal carcinoma (NPC), and explored its correlation to prognosis. METHODS: Expression of ET(A)R in 153 specimens of NPC was detected by SABC immunohistochemistry. RESULTS: Positive rate of ET(A)R was 73.9% in the 153 NPC specimens. No correlation was found between ET(A)R expression and gender, age, T stage, N stage, and TNM stage of the patients. The 3-year overall survival rate, relapse-free survival rate, and distant metastasis-free survival rate were significantly higher in ET(A)R-negative patients than in ET(AR-positive patients (87.5% vs. 73.2%, P = 0.029; 80.0% vs. 57.3%, P = 0.009; and 89.9% vs. 70.4%, P = 0.012), except for local relapse-free survival rate (86.9% vs. 80.2%, P = 0.228). Cox multivariate analysis showed that ET(A)R expression, gender, age, T stage, and N stage were independent prognostic factors, which affected overall survival, relapse-free survival, and distant metastasis. CONCLUSION: ET(A)R expression is an important distant metastasis-related risk factor for patients with NPC; its overexpression indicates poor prognosis.

Long-term survival after cisplatin-based induction chemotherapy and radiotherapy for nasopharyngeal carcinoma: a pooled data analysis of two phase III trials.

PURPOSE: To evaluate the long-term outcome in patients with nasopharyngeal carcinoma (NPC) treated with induction chemotherapy and radiotherapy (CRT) versus radiotherapy alone (RT). PATIENTS AND METHODS: The data from two phase III studies comparing CRT with RT in NPC were updated and pooled together for analysis. A total of 784 patients were included for analysis, with an equal number of patients in both arms. Induction chemotherapy consisted of two to three cycles of cisplatin, bleomycin, and fluorouracil, or cisplatin and epirubicin. RT was given to the nasopharynx and neck using megavoltage radiation (median dose, 70 Gy). The median follow-up time for surviving patients was 67 months. Analysis was based on intention to treat. RESULTS: The addition of induction chemotherapy to RT was associated with a decrease in relapse by 14.3% and cancer-related deaths by 12.9% at 5 years. The 5-year relapse-free survival rate was 50.9% and 42.7% in the CRT and RT arm, respectively (P = .014), and the 5-year disease-specific survival rate was 63.5% and 58.1% in the CRT and RT arm, respectively (P = .029). The 5-year overall survival rate was 61.9% and 58.1% in CRT and RT arm, respectively (P = .092). The incidence of locoregional failure and distant metastases was reduced by 18.3% and 13.3% at 5 years, respectively, with induction chemotherapy. There was no significant difference in the treatment failure patterns between the two arms. CONCLUSION: The addition of cisplatin-based induction chemotherapy to RT was associated with a modest but significant decrease in relapse and improvement in disease-specific survival in advanced-stage NPC. However, there was no improvement in overall survival.

[Clinical value of vascular endothelial growth factor detection in forecasting distant metastasis risk of nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Vascular endothelial growth factor (VEGF)closely relates with the malignancy and metastasis of various kinds of cancers. This study was designed to evaluate the value of VEGF detection in forecasting distant metastasis risk of nasopharyngeal carcinoma(NPC)patients. METHODS: Tumor biopsies,and serum specimens were collected before treatment from 59 pathologically diagnosed NPC patients, hospitalized in our hospital from Mar. 1999 to Feb. 2000. Immunohistochemistry LSAB method was used to detect VEGF in NPC tissues. VEGF in NPC serum was detected by quantitative enzyme-linked immunosorbent assay (ELISA) method. Through follow-up study, the relationship between VEGF and distant metastasis of NPC patients was observed. RESULTS: The expression of VEGF in NPC tissue,and serum positively related with the distant metastasis (P< 0.05). Non-distant metastasis survival rates of different tissue VEGF groups were 100%(-), 95.24%(+), 65.19%(++), and 58.93%(+++), significant difference existed between every 2 groups (P=0.019 3). Non-distant metastasis survival rates of different serum VEGF groups were 82.57% (< 466.78 ng/L), and 59.11% (>/=466.78 ng/L)(P=0.021 1). Multi-prognostic factors analysis showed that VEGF expression in NPC tissue and serum had significant effects on distant metastasis of NPC. CONCLUSIONS: The detection of VEGF either in NPC tissue or in serum could be regarded as a valuable indicator for predicting distant metastasis risk of NPC patients. Combined detection of them could increase the chances of forcasting distant metastasis in NPC patients.

[Treatment of unresectable esophageal carcinoma by stenting with or without radiochemotherapy].

OBJECTIVE: To evaluate the benefits of post-stenting radiotherapy and/or chemotherapy for unresectable esophageal carcinoma. METHODS: Fifty-three patients with unresectable esophageal carcinoma were randomly divided into two groups: patients in group A (n = 27) were treated with stenting alone, and those in group B (n = 26) were treated with stenting followed by radiotherapy and/or chemotherapy. Comparison was made by assessing their survival time, quality of life (QOL), degree of dysphagia, and stenting-related morbidity, respectively. RESULTS: There was no statistically significant improvement in dysphagia and QOL between the two groups. Although there was no difference in the frequency of stenting-related complications, re-stenosis occurred much less frequently in group B patients (P = 0.007). The mean survival time of patients was 245 +/- 41 days and 262 +/- 43 days in group A and group B, respectively. There was no significant difference between the two groups (P = 0.813). CONCLUSION: Besides decreased recurrence of stenosis, post-stenting radiotherapy and/or chemotherapy does not provide additional benefits for survival.

[Expression of topoisomerase IIalpha in nasopharyngeal carcinoma and its clinical significance].

BACKGROUND & OBJECTIVE: TopoisomeraseIIalpha (TopoIIalpha) is a protein in eukaryotic cell with many different roles in DNA duplication and repair. It was reported that the expression level of TopoIIalpha was related to the prognosis of many malignant tumors. The aim of this study was to investigate the relationship of expression of TopoIIalpha in nasopharyngeal carcinoma (NPC) with clinicopathologic factors and its prognostic significance. METHODS: The expression of TopoIIalpha was observed in 114 NPC cases using immunohistochemical staining. All of the patients were divided into two groups according to the expression level of TopoIIalpha. Kaplan-Meier survival analysis was used to analyze the relationship of expression of TopoIIalpha with recurrence and metastasis of tumor after radiotherapy. Cox proportional hazards model analysis was used to analyze the factors related to local recurrence of tumor. RESULTS: The expression of TopoIIalpha in NPC cells ranged from 0 to 90%; the average percentage was (22.63+/-21.92)%. The positive rate of TopoIIalpha was 43.9% (50/114) when 20% was used as the cut-off point. The positive rate of TopoIIalpha was not related to the sex, age, pathological type, and clinical staging. The 3-year relapse-free survival rates of negative group and positive group were 93.1% and 74.3%, respectively (P=0.0027). The 3-year disease-free survival rates of the two groups were 77.9% and 58.9%, respectively (P=0.0091). The metastasis-free survival rates of the two groups were 81.1% and 77.6%, respectively (P=0.566). Cox proportional hazards model analysis showed that the local recurrence of tumor was independently affected by the expression of TopoIIalpha. CONCLUSION: There is a high expression level of TopoIIalpha in a part of NPC.NPC patients with high expression of TopoIIalpha have a higher local recurrence rate and worse prognosis.

[Significance of cell-free Epstein-Barr virus DNA in monitoring prognosis of nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: It has been reported that cell-free Epstein-Barr virus (EBV-DNA) in plasma was useful in diagnosing and monitoring nasopharyngeal carcinoma (NPC). The current study was designed to evaluate the significance of EBV-DNA in monitoring the prognosis of nasopharyngeal carcinoma and to compare with VCA/IgA and EA/IgA. METHODS: EBV-DNA, VCA/IgA, and EA/IgA levels in plasma were detected in different NPC patients after radiotherapy, including 30 distant metastasis patients, 22 locoregional recurrence patients, 24 remission individuals who had been followed up more than 2 years after treatment. EBV-DNA was detected using real-time quantitative PCR system;VCA/IgA and EA/IgA were tested using regular immunofluorescence. In cohort study, the indexes were tested in different radiation periods for the 20 new cases of nasopharyngeal carcinoma. RESULTS: The median plasma EBV-DNA concentration was 135,100 copies/ml (interquartile range: 5,525-1,003,750) in metastasis group, 20,500 copies/ml (interquartile range: 0-58,500) in locoregional recurrence group and 0 copies/ml (interquartile range: 0-0) in continuous remission group (P< 0.05). The levels of VCA/IgA and EA/IgA had no significant difference in different groups. The high level of EBV-DNA concentration in metastasis group was more than that in locoregional recurrence group. At the level of 1,000,000 copies/ml, EBV DNA indicated distant metastasis of NPC with a specificity of 100% and a sensitivity of 27.3%; however, the sensitivity was 0 copies/ml in locoregional recurrence group. For the 20 new patients, EBV DNA concentration gradually decreased in the radiation period, 32,050 copies/ml (interquartile range: 3,880-317,750) before radiation, 0 copies/ml (interquartile range: 0-14,375) when 40 Gy radiation dose and 0 copies/ml (interquartile range: 0-2940) when the radiation finished (P< 0.05). However, the levels of VCA/IgA and EA/IgA had no significant difference. CONCLUSION: The plasma cell-free EBV-DNA is more valuable than VCA/IgA and EA/IgA for monitoring the prognosis of NPC patients.

[Analysis of gene expression patterns of periphery lymphocytes in patients with nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: The periphery T and B lymphocytes are most important immune cells in a body. Analysis for the gene expression profiles of the immune cells will contribute to the understanding of the biological essence of immune suppression. The advanced technique of DNA microarray make it possible to monitor the expression of thousands of genes simultaneously in one hybridization experiment until recently. In this paper, the authors investigated the genes differentially expression in periphery lymphocytes between the patients with Nasopharyngeal Carcinoma(NPC) and health donors to explore the features of gene expression in immune cells of NPC patients. METHODS: The BioDoor10s/D chips containing 2000 spots of cDNAs were used to investigate the difference of the expression. Both the mRNAs from periphery lymphocytes of NPC patients (2 x 10(8)) and health donors(2 x 10(8)) were reversely transcribed to cDNA with the incorporation of fluorescent(cy5 and cy3) labeled dUTP to prepare the hybridization probes. After hybridization, BioDoor10s/D chips were scanned for the fluorescent intensity. The differentially expressed genes were screened. RESULTS: The total of 62 genes has differentially expression in NPC periphery lymphocytes. The number of over- and lower-expressed genes were 5 and 57, respectively. There were 3 genes coding for signal transductive proteins in 5 over-expressed genes. Five genes coding for signal transductive proteins were involved in 9 genes with lowest-expression (cy5/cy3 > or = 0.3). CONCLUSION: There was the consistent tendency toward lower-expressed gene in periphery lymphocytes from the patients with NPC. The disorder in signal transductive function of lymphocytes may be a factor distinguishing NPC immunity from the health one. Improvement of gene expressing profil may also be a way to enhance immune function in tumor patients.

[Positive rate of radionuclide bone imaging and treatment in no ostalgia patients with new nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: According to clinical symptom ostalgia, radionuclide bone imaging was often used to diagnose the bone metastasis of nasopharyngeal carcinoma. But the reports of the positive rate of radionulide bone imaging in no ostalgia patients with newly nasopharyngeal carcinoma is rarely. This study was designed to evaluate the positive rate of radionuclide bone imaging and treatment in no ostalgia patients with new nasopharyngeal carcinoma. METHODS: A total of 104 no ostalgia patients with new nasopharyngeal carcinoma were examined by whole body radionuclide bone imaging. All patients were divided into two groups: group A includes 20 patients which have the abnormal lesions of bone imaging, The abnormal lesions of bone imaging were examined by 5 mm slice bone-target computer tomography. Group B includes 84 patients which have normal bone imaging. These patients were followed up from 6 to 30 months. RESULTS: Twenty patients (19.2%) were with abnormal lesions of bone imaging. The lesions of bone imaging were examined by 5 mm slice bone-target computer tomography. One patients was documeuted bone destraction, 2 patients were deteriorative, other 17 patients were no abnormal. With a follow up from 6 to 10 months, 11 patients appeared ostalgia. The lesions of bone imaging had developed when examined by bone imaging again, 84 (81.8%) patients were negative; but with a follow up from 4 to 20 months, 9 patients appeared ostalgia and there were new lesions of bone imaging when examined by bone imaging again. There was a higher significant difference in incidence of bone metastasis in group A and group B. (P < 0.01) The patients with ostalgia received local radiotherapy or combining therapy. CONCLUSION: The rate of radionuclide bone imaging in no ostalgia patients with new nasopharyngeal carcinoma was 19.2%. The incidence of bone matastasis in positive patients of bone imaging was higher than that in negative. Two cycles of neoadjuvant chemotherapy can not reduced the appearing rate of ostalgia. Acording to clinical symptom, The following up can be selected to the no ostalgia patient of positive bone imaging with newly nasopharyngeal carcinoma. But computer tomography can not determined the faulse positive of radionuclide bone imaging.

Prognostic significance of DNA ploidy and proliferative indices in patients with nasopharyngeal carcinoma.

BACKGROUND & OBJECTIVE: Radiotherapy is the fundamental treatment for the patients with nasopharyngeal carcinoma (NPC). Altered fraction radiotherapy and chemotherapy have become a part of combined regimes for advanced disease judged by clinicopathological criteria. However, the known prognostic factors reveal a wide range of treatment outcomes with NPC. This study was designed to investigate whether the deoxyribonucleic acid (DNA) content or proliferative indices (PIs) of the tumors in NPC patients detected with flow cytometry (FCM) could be an additional prognostic reference. METHODS: Two hundred and five cases of paraffin-embedded archival NPC biopsies obtained from the patients treated from 1994 to 1995 were tested for the analysis of DNA ploidy, and proliferative indices including S-phase fraction(SPF), G2/M-phase fraction (G2/MF), and proliferative fraction (PF). DNA ploidy and PIs of tumors were correlated to the clinical parameters and prognosis of the patients. RESULTS: Of the 205 tested cases, 117 tumor biopsies were satisfied the guideline criteria of the DNA Cytometry Consensus Conference. Thirty-five tumors (30%) were aneuploid (AN) and eighty-two (70%) were DNA diploid (DP). DNA ploidy and PIs were not significantly associated with age, sex, pathological classification, T/N classification, and clinical stage. AN tumors had a significantly higher SPF and PF than the DP tumors did (P = 0.023, P = 0.012, respectively). There was a significant difference in 5-year relapse-free-survival (RFS) between the patients with DP and those with AN (62% versus 43%, P = 0.035). There was a significant difference in 5-year RFS among low, middle, and high SPF and PF groups(81% versus 61% versus 21%, 77% versus 62% versus 33%, respectively) (P = 0.000, P = 0.048, respectively). There were no significant differences in 5-year RFS among the low, middle, and high G2/MF groups (55% versus 58% versus 54%, P = 0.8617). CONCLUSION: DNA ploidy, SPF, and PF could be predictors of prognosis for NPC patients. Thus, determination of these indices can be used as an additional reference for clinicians to identify a poor prognostic NPC individual together with clinic pathological parameters.

Identifying cancer-related genes in nasopharyngeal carcinoma cell lines using DNA and mRNA expression profiling analyses.

The goals of this study were to evaluate the potential of detecting cryptic amplification and deletion of cancer-related genes using array-based comparative genomic hybridization (CGH), and to identify candidate cancer genes by combined parallel analyses of copy number and gene expression profiles in nasopharyngeal carcinoma (NPC) cell lines. We established global DNA copy number and mRNA expression profiles on human NPC cell lines using a high-density cDNA microarray. The DNA copy number alterations detected by array CGH were compared to the DNA copy number variations identified by metaphase CGH. A cryptic amplification at 3q26 was detected by array CGH, which was not found by metaphase CGH. By amplicon mapping and parallel analyses of DNA copy number and mRNA expression levels, we identified several candidates which could be important mediators in tumor formation or progression. Taken together, the combination of copy number and gene expression profiling using cDNA microarrays provides an improved strategy for gene discovery in human cancer.

Met protein expression level correlates with survival in patients with late-stage nasopharyngeal carcinoma.

Met tyrosine kinase, the receptor for HGF/SF, is important in various cellular functions, including proliferation, mitogenesis, formation of branching tubules, angiogenesis, and tumor cell invasion and metastasis. However, the role of Met/HGF signaling pathway in nasopharyngeal carcinoma (NPC) has not been evaluated. In this study, we determined the expression profile and clinical correlation of Met/HGF in 66 cases of advanced NPC and the activation mechanisms of Met receptor in five NPC cell lines. Immunofluorescent staining and quantitative image analysis showed that the Met protein was expressed throughout the tumors and normal nasopharyngeal epithelia. Compared with NPC, the Met expression level was higher in columnar nasopharyngeal epithelium but lower in squamous nasopharyngeal epithelium. The normal interstitial stromal tissue expressed the lowest level of Met protein. HGF was detected mainly in the normal interstitial tissue surrounding the tumor. Met protein expression level was inversely correlated with patients' survival time; the correlation coefficient was -0.319 (P = 0.009). The mean survival time was 118 months in low Met expression group versus 52 months in high expression group (P = 0.0004). The cumulative 5-year survival rate was 77.68% in low expression group versus 38.24% in high expression group. The clinical stage was also significantly more advanced in high Met expression group. In the multivariate analysis, both clinical stage and Met protein expression level were independent prognostic indicators for patient survival. All of the five NPC cell lines tested did not express hgf mRNA but expressed met mRNA, and tyrosine phosphorylation of Met protein was mainly induced by exogenous HGF stimulation in these cells. No mutation was found in the tyrosine kinase and the juxtamembrane domains of Met receptor in the five NPC cell lines tested. These results indicate that: (a) high Met protein expression level correlates with poorer survival in late-stage NPC and serves as an independent prognostic indicator; and (b) the Met receptor in NPC is activated by its paracrine ligand HGF from the interstitial tissues rather than by an autocrine loop or its activating mutation.