Search

Supplementary Figure S8

Supplementary Table S7

Purpose:Adults with T-cell lymphoblastic lymphoma (T-LBL) generally benefit from treatment with acute lymphoblastic leukemia (ALL)-like regimens, but approximately 40% will relapse after such treatment. We evaluated the value of CpG methylation in predicting relapse for adults with T-LBL treated with ALL-like regimens.Experimental Design:A total of 549 adults with T-LBL from 27 medical centers were included in the analysis. Using the Illumina Methylation 850K Beadchip, 44 relapse-related CpGs were identified from 49 T-LBL samples by two algorithms: least absolute shrinkage and selector operation (LASSO) and support vector machine–recursive feature elimination (SVM-RFE). We built a four-CpG classifier using LASSO Cox regression based on association between the methylation level of CpGs and relapse-free survival in the training cohort (n = 160). The four-CpG classifier was validated in the internal testing cohort (n = 68) and independent validation cohort (n = 321).Results:The four-CpG–based classifier discriminated patients with T-LBL at high risk of relapse in the training cohort from those at low risk (P < 0.001). This classifier also showed good predictive value in the internal testing cohort (P < 0.001) and the independent validation cohort (P < 0.001). A nomogram incorporating five independent prognostic factors including the CpG-based classifier, lactate dehydrogenase levels, Eastern Cooperative Oncology Group performance status, central nervous system involvement, and NOTCH1/FBXW7 status showed a significantly higher predictive accuracy than each single variable. Stratification into different subgroups by the nomogram helped identify the subset of patients who most benefited from more intensive chemotherapy and/or sequential hematopoietic stem cell transplantation.Conclusions:Our four-CpG–based classifier could predict disease relapse in patients with T-LBL, and could be used to guide treatment decision.

Supplementary Figure legend

Purpose: Adults with T-cell lymphoblastic lymphoma (T-LBL) generally benefit from treatment with acute lymphoblastic leukemia (ALL)-like regimens, but approximately 40% will relapse after such treatment. We evaluated the value of CpG methylation in predicting relapse for adults with T-LBL treated with ALL-like regimens. Experimental Design: A total of 549 adults with T-LBL from 27 medical centers were included in the analysis. Using the Illumina Methylation 850K Beadchip, 44 relapse-related CpGs were identified from 49 T-LBL samples by two algorithms: least absolute shrinkage and selector operation (LASSO) and support vector machine–recursive feature elimination (SVM-RFE). We built a four-CpG classifier using LASSO Cox regression based on association between the methylation level of CpGs and relapse-free survival in the training cohort (n = 160). The four-CpG classifier was validated in the internal testing cohort (n = 68) and independent validation cohort (n = 321). Results: The four-CpG–based classifier discriminated patients with T-LBL at high risk of relapse in the training cohort from those at low risk (P < 0.001). This classifier also showed good predictive value in the internal testing cohort (P < 0.001) and the independent validation cohort (P < 0.001). A nomogram incorporating five independent prognostic factors including the CpG-based classifier, lactate dehydrogenase levels, Eastern Cooperative Oncology Group performance status, central nervous system involvement, and NOTCH1/FBXW7 status showed a significantly higher predictive accuracy than each single variable. Stratification into different subgroups by the nomogram helped identify the subset of patients who most benefited from more intensive chemotherapy and/or sequential hematopoietic stem cell transplantation. Conclusions: Our four-CpG–based classifier could predict disease relapse in patients with T-LBL, and could be used to guide treatment decision.

We aimed to establish a discriminative gene-expression-based classifier to predict survival outcomes of T-cell lymphoblastic lymphoma (T-LBL) patients. After exploring global gene-expression profiles of progressive (n = 22) vs. progression-free (n = 28) T-LBL patients, 43 differentially expressed mRNAs were identified. Then an eleven-gene-based classifier was established using LASSO Cox regression based on NanoString quantification. In the training cohort (n = 169), high-risk patients stratified using the classifier had significantly lower progression-free survival (PFS: hazards ratio 4.123, 95% CI 2.565–6.628; p

New prognostic factors are needed to establish indications for haematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) for T-cell lymphoblastic lymphoma (T-LBL) patients. We used microarray to compare T-LBL tissue samples (n = 75) and fetal thymus tissues (n = 20), and identified 35 differentially expressed miRNAs. Using 107 subjects as the training group, we developed a five-miRNA-based classifier to predict patient survival with LASSO Cox regression: lower risk was associated with better prognosis (disease-free survival (DFS): hazard ratio (HR) 4.548, 95% CI 2.433–8.499, p

Microinvasive carcinoma (MIC) of the breast is a rare lesion. The clinicopathologic features and biologic behavior of MIC are unclear. Whether MIC is a distinct entity or an interim stage in the progression from ductal carcinoma in situ (DCIS) to invasive breast carcinoma (IBC) remains to be determined. A retrospective review of clinicopathologic features and analysis of the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 in patients with MIC (90 cases), DCIS (268 cases) and IBC (1504 cases) was performed. Most MICs (93.3%) exhibited an intermediate to high nuclear grade, and this proportion was larger than that of DCIS (62.7%, P < 0.001) or IBC (85.4%, P = 0.036). The incidence of sentinel lymph node metastasis in MIC (12.5%) was higher than that of DCIS (1.6%, P < 0.001), but much lower than that of IBC (39.7%, P < 0.001). MICs had higher expression of HER-2 and lower expression of ER and PR compared to DCIS and IBC; and MIC was more likely to present with a HER-2+ subtype. Furthermore, DCIS exhibited greater HER-2 overexpression or gene amplification (P < 0.001) levels and lower proliferation index of Ki-67 (P < 0.001) compared to IBC. Our results suggest that the clinicopathologic and molecular phenotype of MIC are different from DCIS and IBC. Thus, MIC may be a distinct entity rather than an interim stage in the progression from DCIS to IBC. The prognosis of MIC and the biologic behavior of this uncommon subset need to be further explored.

We aimed to establish a discriminative gene-expression-based classifier to predict survival outcomes of T-cell lymphoblastic lymphoma (T-LBL) patients. After exploring global gene-expression profiles of progressive (n = 22) vs. progression-free (n = 28) T-LBL patients, 43 differentially expressed mRNAs were identified. Then an eleven-gene-based classifier was established using LASSO Cox regression based on NanoString quantification. In the training cohort (n = 169), high-risk patients stratified using the classifier had significantly lower progression-free survival (PFS: hazards ratio 4.123, 95% CI 2.565-6.628; p 0.001), disease-free survival (DFS: HR 3.148, 95% CI 1.857-5.339; p 0.001), and overall survival (OS: HR 3.790, 95% CI 2.237-6.423; p 0.001) compared with low-risk patients. The prognostic accuracy of the classifier was validated in the internal testing (n = 84) and independent validation cohorts (n = 360). A prognostic nomogram consisting of five independent variables including the classifier, lactate dehydrogenase levels, ECOG-PS, central nervous system involvement, and NOTCH1/FBXW7 status showed significantly greater prognostic accuracy than each single variable alone. The addition of a five-miRNA-based signature further enhanced the accuracy of this nomogram. Furthermore, patients with a nomogram score ≥154.2 significantly benefited from the BFM protocol. In conclusion, our nomogram comprising the 11-gene-based classifier may make contributions to individual prognosis prediction and treatment decision-making.

Background: Adults with T-cell lymphoblastic lymphoma (T-LBL) generally benefit from treatment with acute lymphoblastic leukemia (ALL)-like regimens, but approximately 40% will relapse after such treatment. We evaluated the value of CpG methylation in predicting relapse for adults with T-LBL treated with ALL-like regimens. Methods: A total of 549 adults with T-LBL from 27 medical centers were included in the analysis. Using the Illumina Methylation 850K Beadchip, 44 relapse-related CpGs were identified from 49 T-LBL samples by two algorithms, Least Absolute Shrinkage and Selector Operation (LASSO) and Support Vector Machine-Recursive Feature Elimination (SVM-RFE). We built a four-CpG classifier using LASSO Cox regression based on association between the methylation level of CpGs and relapse-free survival (RFS) in the training cohort (n=160).The four-CpG classifier was validated in the internal testing cohort (n=68) and independent validation cohort (n=321). Findings: The four-CpG-based classifier discriminated T-LBL patients at high risk of relapse in the training cohort from those at low risk (p

Supplemental Digital Content is available in the text, Ductal carcinoma in situ (DCIS) represents a heterogeneous disease in its histologic appearance and biological potential. Some women treated for DCIS subsequently develop invasive breast cancer. DCIS with microinvasion is considered as the interim stage in the progression from DCIS to invasive breast cancer. Analysis of the differences between DCIS and DCIS with microinvasion may aid in understanding the characteristic of DCIS with microinvasion and identifying biological factors determining progression of DCIS to invasive disease. Retrospective analysis of 219 cases between 2012 and 2018 was performed in our institution. The pathological results and axillary lymph nodes status were collected. Analysis of the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 in pure DCIS (164 cases), and DCIS with microinvasion (55 cases) using immunohistochemistry. DCIS with microinvasion had a higher nuclear grade (P

The factors affecting performance of fractured wells are analyzed in this work. The static and dynamic geologic data of fractured well and fracturing treatment parameters obtained from 51 fractured wells in sand reservoirs of Zhongyuan oilfield are analyzed by applying the grey correlation method. Ten parameters are screened, including penetrability, porosity, net thickness, oil saturation, water cut, average daily production, and injection rate, amount cementing front spacer, amount sand-carrying agent and amount sand. With the novel Radial Basis Function neural network model based on immune principles, 13 parameters of 42 wells out of 51 are used as the input samples and the stimulation ratios as the output samples. The nonlinear interrelationship between the input samples and output samples are investigated, and a productivity prediction model of optimizing fracture design is established. The data of the rest 7 wells are used to test the model. The results show that the relative errors are all less than 7%, which proves that the novel Radial Basis Function neural network model based on immune principles has less calculation, high precision and good generalization ability.

Schwannoma of breast is a relatively uncommon disease characterized by painless and slow growing. We report a case of a 28-year-old female who present a mass of the right breast. Ultrasonography revealed a well-circumscribed and inhomogeneous hypoechoic mass under the skin of the breast. Then a biopsy and immunohistochemical analysis were performed. The results were suggestive for cellular schwannoma of breast. The tumour was removed successfully and the patient has been followed-up for six months with no evidence of recurrence. Cellular schwannoma is a rare benign neoplasm without metastasis. Distinction cellular schwannoma from other malignant tumours is very important. It is necessary to combine strict criteria on histological, immunohistochemical analysis, biological behavior, image examination and clinical features for the final diagnosis.

Although human breast ducts and terminal ductal lobular units (TDLUs) share the same cell types, ample evidence shows that TDLUs are the predominant site for the origin of breast cancer. Yet, there is still limited information concerning the molecular mechanisms. Analysis of transcriptomic profiles in TDLUs may provide insight into early breast tumorigenesis. We compared genome-wide expression profiles of 8 matched sets of breast main duct and TDLU samples, using significance analysis of microarray (SAM) software to screen differentially expressed genes (DEGs) with fold-change >2.0 and q-value

To study the etiology, clinical and pathologic characteristics of periductal mastitis with fistula and estimate the effect of anti-mycobacterial agents for periductal mastitis with fistula.Totally 27 patients of periductal mastitis with fistula received anti-mycobacteria drugs therapy from December 2008 to September 2011 were analyzed retrospectively. All of the patients were female. The mean age at onset was 28 years (range 15 to 40 years old). The main clinical manifestation of the 27 patients was breast fistula, including 21 patients with single fistula and 6 patients with multiple fistula. Three patients manifested with pure fistula, 14 patients with both fistula and lump, 10 patients with fistula, lump and abscess. The samples including pus or tissues of all patients were underwent bacteria culture and all patients core needle biopsy. All patients were given primary anti-mycobacteria drugs therapy, parts of patients received surgery based on the evaluation of medical treatment.The common bacteria culture of all patients failed to demonstrate any causative microorganism. Four cases were selected randomly to undergo PCR of mycobacteria, only one case was identified as Massiliense in bacteria culture of mycobacteria. Twenty-seven patients with periductal mastitis with fistula were treated with anti-mycobacterial agents (isoniazid, rifampicin and ethambutol or pyrazinamide of triple oral drugs) for 1 to 3 months, the fistula of all 27 patients were closed well. Sixteen patients were treated with the agents only and cured. Eleven patients received surgical treatment after treated with the medical agents. None of the patients were given mastectomy. All patients had no reccurence until now.The periductal mastitis with fistula has a closely relationship with the infection of nontuberculosis mycobacteria. Those patients could be treated with triple anti-mycobacterial agents and could also avoided mastectomy.

To evaluate the clinical application of high-frequency ultrasound-guided vacuum-assisted biopsy for breast microcalcifications.Sixty-six patients with 70 lesions of microcalcifications detected at mammography underwent high-frequency ultrasound-guided vacuum-assisted biopsy from July 2009 to October 2010. All patients were female, aged 24 to 61 years (median age 40 years). Among 70 lesions of microcalcifications, unilateral lesions were 62 cases and bilateral lesions were 4 cases. The clinical factors that affected the success of biopsy were investigated by χ(2) test and Logistic regression analysis.Among 70 lesions of microcalcifications, the successful rate of biopsy was 72.9% (51/70). The biopsy successful rate of microcalcifications without and with masses were 65.2% (30/46) and 87.5% (21/34) respectively (χ(2) = 3.960, P = 0.047). The biopsy successful rate of microcalcifications of maximal diameter more than 5 mm was higher than that of maximal diameter less than 5 mm (88.9% vs. 55.9%, χ(2) = 9.633, P = 0.002). The Logistic regression analysis showed that the types and maximal diameter of microcalcifications were the main factors that affected the success of biopsy.The clinical application of high-frequency ultrasound-guided vacuum-assisted biopsy was an effective option for the diagnosis of breast microcalcifications, especially for the type of microcalcifications with masses and the maximal diameter more than 5 mm.

To evaluate the application of the immunohistochemistry (IHC) and the fluorescence in situ hybridization (FISH) in detecting the amplification and the expression of HER-2 gene in the breast cancer patients.Sixty-six cases of paraffin-embeded breast cancer samples with overexpression, low or no expression of HER-2 gene as detected by IHC were analyzed for HER-2 gene amplification using FISH.Among the 42 samples with HER-2 gene overexpression (3+/2+) detected by IHC, 31 showed positive HER-2 gene amplification and 11 showed negative HER-2 gene amplification in FISH. In the 24 samples with low or no HER-2 gene expression (1+/-) detected by IHC, no HER-2 gene amplification was detected by FISH. The results of the two testing methods showed a good consistency with the kappa coefficient of 0.672 (P0.001). We also found that the 17 chromosome polysomy in 42% of the samples and the incidence of 17 polysomy was significantly higher in the HER-2 gene overexpression (3+/2+) group than in low or no HER-2 gene expression (1+/-) group (chi(2)=4.688, P=0.03).IHC can be used as a screening method for detecting HER-2 gene amplification, and FISH should be performed in cases of HER-2 gene overexpression (3+/2+) as detected by IHC.

To investigate the clinical and pathological features of non-Hodgkin's lymphoma (NHL) and to evaluate the applicability of the new WHO classification of lymphoid neoplasms.According to the new WHO classification, a total of 500 cases of non-Hodgkin's lymphoma diagnosed during the period 1992 - 2003 were reviewed and reappraised with their morphological, immunological and clinical characteristics. Clinical survival analysis was performed in 156 cases that accompanied with follow-up data.Among 500 cases previously diagnosed as lymphomas, 493 cases (98.6%) were confirmed to be NHL, of which B-cell neoplasms was 69.0% and T/NK-cell neoplasms 29.8%. Overall, 6 subtypes including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), unspecified peripheral T-cell lymphoma (PT-un), precursor T-lymphoblastic lymphoma (T-LBL), extranodal marginal zone B-cell lymphoma of MALT type (MALT) and B-small lymphocytic lymphoma (B-SLL) were among the most common subtypes. In pediatric and young patient populations, the most common subtypes were LBL, DLBCL and Burkitt's lymphoma. The frequency of LBL in all patients, especially in the juniors, was much higher than those reported outside Mainland China, and the frequency of FL was much higher than the reported in Mainland China. The frequency of FL was much higher than the reported in Mainland China. Clinical survivals among different histological subtypes of NHL varied considerably with statistic significance (P0.001). Marginal zone B-cell lymphoma and SLL demonstrated the best prognosis, LBL and PT-un both the worst, whereas DLBCL and FL had an intermediate prognosis, however, subgrouping of FL according to WHO classification did not reveal a significant survival difference (P0.05).Basing upon the results of a comprehensive survey on the morphologic features, immunophenotyping and clinical data of the above cases, the new WHO classification of lymphoid neoplasms is practical and easily applicable for routine pathological evaluation of lymphoproliferaive disorders and in guiding the clinical management. It appears that the diagnostic and grading criteria for FL in Mainland China need to be re-evaluated.

The plasma Epstein-Barr virus DNA (EBV-DNA) level has been found to be an indicator for staging and prognosis of nasopharyngeal carcinoma (NPC).The EBV-DNA level in plasma, peripheral blood cells (PBC) and neoplastic tissues was quantitatively analyzed and potential associations with clinical parameters of NPC were investigated.The plasma EBV-DNA detecting rate and level in NPC (92%, 82,500 copies/ml) was significantly higher than that in NPC after treatment (19%, 0 copy/ml) and in controls (12%, 0 copy/ml) (p0.001); while there was no significance of the PBC EBV-DNA detecting rate and EBV-DNA load in NPC before (24%, 0 copy/actin) and after treatment (14%, 0 copy/actin), and in controls (16%, 0 copy/actin). The plasma EBV-DNA level was not correlated to the PBC EBV-DNA load in NPC before (p = 0.92) and after treatment (p = 0.267), and in controls (p = 0.735). The EBV-DNA level in NPC tumor (27.8 copies/actin) was significantly higher than that in nasopharyngitis and was positively correlated to the ratio of EBER1-positive cells on the NPC section (p = 0.001). The plasma EBV-DNA level was significantly increased in TNM stages I, II, III and IV NPC, whereas there was no significant difference of PBC EBV-DNA load in different stage NPC.Our results indicate that plasma EBV-DNA is a more sensitive and reliable biomarker than PBC EBV-DNA for diagnosis, staging and therapeutic effect evaluation at a molecular level in NPC clinical practice. Plasma EBV-DNA may derive from the cancer cells and PBC EBV-DNA from circulating mononuclear cells in NPC patients.

Mitochondrial DNA (mtDNA) has a high mutation rate due at least in part to a lack of protective histones and an inefficient DNA repair system. The most frequently change in mtDNA is the so-called Common Deletion (CD), which accumulates in patients with heteroplasmic mtDNA mutations and in normal individuals during aging. In this study, wild type mtDNA (WT-mtDNA) and mitochondrial DNA with CD (CD-mtDNA) were quantitatively analyzed in different nasopharynx lesions. A novel type of CD-mtDNA (4981 bp) was detected significantly higher in nasopharyngeal carcinoma (NPC) (93%, 54/58) than in nasopharyngitis (60%, 28/47) and the paired white blood cells (WBC) (26%, 8/31). The ratio of CD-mtDNA to WT-mtDNA in NPC (0.000625, median) was ten times that in nasopharyngitis (0.000064, median) (P=0.003), and was significantly higher than that in paired WBC (0.000000, median) (P=0.000). The CD/WT-mtDNA ratio was 0.000564 (quartile range, 0.000184-0.000919) in late stage NPC, which was nearly three times the ratio in early stage NPC (0.000164, quartile range, 0.000042-0.000353) (P=0.015, Mann-Whitney Test). In NPC patients with ages

To quantitative analysis of Epstein-Barr virus (EBV) DNA levels in plasma, peripheral blood cells (PBCs) and tumor tissue in nasopharyngeal carcinoma (NPC), to investigate the relationship between EBV-DNA levels and clinical parameters.Blood of 150 primary NPC and 49 corresponding tumor tissues, 47 nasopharyngitis tissues and blood of 75 controls were entered this investigation. Plasma and PBCs were isolated for quantitative detection of EBV-DNA by using real-time quantitative PCR (RQ-PCR). The paraffin-embedded tissue sections were conducted to quantitative detection of EBV-DNA, and EBER1 in situ hybridization (ISH) for calculating the percentage of positive cells on the tissue section.Plasma EBV-DNA levels and detecting rate in NPC before treatment (median 82 500 copies/ml, 92%) were significantly higher than that in NPC after treatment (median 0 copy/ml, 19%) and in controls (median 0 copy/ml, 12%) (P0.05), whereas there was no significant difference between NPC after treatment and controls (P0.05). There was no significant difference of PBCs EBV-DNA load and detecting rate in NPC before (0 copy/actin, 24%) and after treatment (0 copy/actin, 14%), as well as in controls (0 copy/actin, 16%) (P0.05). Plasma EBV-DNA level was not correlated to PBCs EBV-DNA load in NPC before (P = 0.92) and after treatment (P = 0.27), and controls (P = 0.74). EBV-DNA level (27.8 copies/actin) in NPC tumor tissues was significantly higher than that in nasopharyngitis (0 copy/actin) (P0.05), and was positively correlated to the ratio of EBER1 positive cells to total cells on the NPC section. In NPC patients, plasma EBV-DNA level was significantly increased in TNM stage I (2500 copies/ml), II (32 590 copies/ml), III (86 000 copies/ml) and IV (166 200 copies/ml), whereas there was no significantly difference of PBCs EBV-DNA loads in difference stages of NPC.Plasma EBV-DNA level is a more sensitive and reliable biomarker than PBCs EBV-DNA loads for reflection the tumor volumes in NPC patients. Plasma EBV-DNA detection will improve TNM staging in NPC clinical practice on molecular level.

To study the deletion of mitochondiral DNA in hepatocellular carcinoma and hepatocellular nodular hyperplasia and its significance in the development of cancer.Deleted mtDNA (CD-mtDNA) and wild type mtDNA (WT-mtDNA) were quantitatively analyzed by using real-time PCR in 27 hepatocellular carcinomas (HCC) and corresponding noncancerous liver tissues and 27 hepatocellular nodular hyperplasiae (HNH).A novel CD (4 981 bp) was detected in 85% (23/27) and 83%(22/27) of HCC and HNH tumor tissues, respectively, which were significantly higher than that in paired noncancerous liver tissues (57%, 15/27) (P0.05). The CD/WT-mtDNA ratio in HCC tumors was 0.00092 (median, interquartile range, 0.0001202-0.00105), which was significantly higher than that in paired noncancerous liver tissues (median, 0.000, quartile range, 0-0) (P=0.002, Mann-Whitney Test), and was 25 of times of that in HNH tissues (median, 0.0000374, quartile range, 0-0.0004225) (P=0.002, Mann-Whitney test).CD-mtDNA mutation plays an important role in the development and progression of HCC.

BACKGROUND Serologic measurement of antibodies to Epstein–Barr virus (EBV) immunoglobulin A/viral capsid antigen (IgA/VCA) and early antigen (IgA/EA) has been used widely to screen for nasopharyngeal carcinoma (NPC) in China. Recently, it was found that plasma EBV DNA concentration is an indicator for the staging and prognosis of patients with NPC. To determine whether there is a correlation between plasma EBV DNA levels and serum levels of IgA/VCA, the authors measured both in patients with NPC and in a control group. METHODS Real-time polymerase chain reaction was used for quantitative analysis of plasma EBV DNA concentration, and enzyme-linked immunoadsorbent assay was used to measure EBV VCA/IgA in patients with primary NPC (n = 120 patients), locally recurrent NPC (n = 8 patients), and distant metastatic NPC (n = 21 patients) among 76 patients with NPC after the completion of radiotherapy, in 60 patients with NPC in clinical remission, in 38 patients with non-NPC tumors, and in 47 control individuals. RESULTS The median plasma EBV DNA levels were 6200 copies/mL, 9200 copies/mL, and 2050 copies/mL in patients with primary, locally recurrent, and distant metastatic NPC, respectively, but declined to 0 copies/mL in patients with clinically remissive NPC, in patients who completed radiotherapy, in patients with non-NPC tumors, and in the control group. In contrast, EBV VCA/IgA titers and detection rates remained high in all NPC groups. Plasma EBV DNA levels were significantly higher in patients who had serum VCA/IgA titers ≥ 1:640 (median, 83,450 copies/mL) compared with the levels in patients who had titers ≤ 1:320 (median, 17,200 copies/mL). Patients with NPC who had advanced TNM stage (Stages III and IV; median, 8530 copies/mL) and T classification (T3 and T4 tumors; median, 8530 copies/mL) had significantly higher plasma EBV DNA levels compared with patients who had early TNM stage (Stages I and II; median, 930 copies/mL) and T classification (T1 and T2 tumors; median, 3700 copies). Patients who had advanced TNM stage NPC had significantly higher mean VCA/IgA titers (1:424) compared with patients who had early TNM stage NPC (1:246), but there was no correlation between IgA/VCA titer and T or N classification of NPC. CONCLUSIONS The results suggest that plasma EBV DNA detection is a more sensitive and specific marker than the serum IgA/VCA titer for the diagnosis and monitoring of patients with NPC. These findings provide convincing evidence for the use of plasma EBV DNA measurements for the early diagnosis and staging of NPC as well as for monitoring recurrence and metastasis of this tumor. Cancer 2004. © 2004 American Cancer Society.

Nasopharyngeal carcinoma (NPC) is closely related to Epstein-Barr virus (EBV) infection. Recently, it was reported that EBV DNA could be detected in the plasma or serum of NPC patients, but the clinical significance of EBV DNA concentration for monitoring of tumor recurrence and metastasis in NPC patients after radiotherapy has not been reported. This study was designed to quantitatively analyze the plasma EBV DNA concentration in NPC patients after radiotherapy, and to evaluate its application for monitoring of tumor recurrence and metastasis.Ninety NPC outpatients after radiotherapy in Cancer Center, Sun Yat-sen University were followed up. The plasma EBV DNA were analyzed by using fluorescent quantitative PCR technique, and the quantity of plasma EBV DNA were compared between recurrent and clinical remission NPC patients.Ninety-six point seven percent (29/30) of recurrent and metastatic patients were detectable for plasma EBV DNA, with median concentration of 2650 copies/ml (range:0-5900000), whereas only 12%(7/60) of the clinical remission patients were detectable for plasma EBV DNA, with median concentration of 0 copy/ml (range:0-71000). The detectable proportion and concentration in recurrent and metastatic NPC patients were significantly higher than that in clinical remission NPC patients (P0.01). Three of the clinical remission NPC patients with elevated EBV DNA copy were confirmed for tumor local recurrence or metastasis after further 3-4 month follow-up.The results suggest that plasma EBV DNA detection may be a sensitive tumor marker for monitoring tumor recurrence and metastasis of NPC patients after radiotherapy.