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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

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.

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

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.

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.