Zhuo-Ying Wang

Fudan University, Shanghai, Shanghai Shi, China

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Publications (16)33.82 Total impact

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    ABSTRACT: Papillary thyroid cancer (PTC) often presents as multifocal. However, the association of multifocality with poor prognosis remains controversial. The aim of this retrospective study was to identify the characteristics of PTC with multiple foci and to evaluate the association between multifocality and prognosis. We reviewed the medical records of 496 patients who underwent total thyroidectomy for PTC. Patients were classified as G1 (1 tumor focus), G2 (2 foci), and G3 (3 or more foci). We analyzed the clinicopathological features and clinical outcomes in each classification. A Cox regression model was used to assess the relationship between multifocality and recurrence or cancer mortality. The G1, G2 and G3 groups included 287, 141 and 68 patients, respectively. The mean age was 47.1 +/- 16.1 yr in G1, 41.1 +/- 18.4 yr in G2, and 35.5 +/- 15.9 yr in G3 and differed significantly among the 3 groups (p = 0.001). The proportion of extrathyroidal extension, central lymph node metastasis (CLNM), and lateral lymph node metastasis (LLNM) in the G1 to G3 groups increased with increasing number of tumor foci. The Kaplan-Meier curves revealed that G3 had the shortest recurrence-free survival, and differences were significant among the 3 groups (p = 0.001, Log Rank test). Furthermore, cancer-specific survival rates decreased significantly with increasing number of tumor foci (p = 0.041). Independent predictors of recurrence by multivariate Cox analysis included >3 tumor foci [HR 2.60, 95% confidence interval (CI) 1.53-4.39, p = 0.001] and extrathyroidal extension (HR 1.95, CI 1.12-3.38, p = 0.018). An increase in the number of tumors is associated with a tendency toward more aggressive features and predicts poor prognosis in PTC.
    BMC Cancer 12/2014; 14(1):914. · 3.33 Impact Factor
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    ABSTRACT: MicroRNAs (miRNAs) are small non-coding RNA molecules that are involved in a variety of cellular functions. Single nucleotide polymorphisms (SNPs) have been identified in mature miRNAs (mmSNPs), some of which have been linked to cancer risk; however, it is unclear which mmSNPs contribute to the susceptibility to thyroid tumors. In the present study, we examined the influence of selected mmSNPs on the risk of thyroid tumor. After systematic in silico screening, seventeen mmSNPs were identified and genotyped in a Chinese population including 828 patients with papillary thyroid cancer (PTC), 488 patients with benign thyroid tumor (BN), and 1038 cancer-free controls. Multivariate logistic regression analyses were conducted to evaluate the association of SNP genotypes and alleles with the risk of developing PTC and BN. Three SNPs (rs67106263 in mir-3144, GA versus GG, OR = 1.35, 1.09-1.68; rs4919510 in mir-608, CC versus GG/GC, OR = 0.76, 0.60-0.97; and rs79402775 in mir-933, AA versus GG/GA, OR = 1.76, 1.00-3.12) were associated with PTC risk. A combined effect of unfavorable genotypes was observed to give increased PTC risk in a dose-dependent manner. In addition, three SNPs (rs10061133 in mir-449b, rs79402775 in mir-933 and rs4919510 in mir-608) showed at least borderline correlations with the risk of BN. False-positive report probability was assessed for significant findings. The rs67106263 SNP was associated with the expression level of mir-3144 in thyroid tissue. These results indicate that mmSNPs may contribute to genetic susceptibility to thyroid tumors. Large validation and functional studies are required to further explore the role of mmSNPs in carcinogenesis.
    Endocrine. 11/2014;
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    ABSTRACT: (1) BACKGROUND: The genetic predisposition to papillary thyroid cancer (PTC) is far from clearly elucidated. Rs2292832 is a genetic polymorphism that located in the precursor of mir-149 and has been studied in diverse cancers. Thus far, the role of rs2292832 in PTC tumorigenesis and progression was unclear; (2) METHOD: Rs2292832 was genotyped in 838 PTCs, 495 patients with thyroid benign tumors (BNs) and 1006 controls in a Chinese Han population. Clinicopathological data was collected and compared. The expression level of mature mir-149 was examined in 55 normal thyroid tissue samples; (3) RESULTS: The CC genotype of rs2292832 was significantly associated with an increased risk of PTC compared with TT homozygote (OR = 1.60, 95% CI: 1.72-2.20, p = 0.003) and TT/TC combined genotype (OR = 1.54, 95% CI: 1.14-2.09, p = 0.005). Rs2292832 is an independent risk factor correlated with tumor invasion (p = 0.006) and higher T stage in PTC patients (p = 0.007), but uncorrelated with short-term disease persistence of PTC. PTC subjects carrying CC genotype have lower mir-149-5p expression than those with TC genotype (p = 0.002). Twelve predicted target genes have been identified by collaboratively using computational tools; (4) CONCLUSION: Rs2292832 was possibly involved in the susceptibility and local progression of PTC in Chinese patients, by altering the expression level of mir-149-5p and its target genes.
    International Journal of Molecular Sciences 01/2014; 15(11):20968-81. · 2.46 Impact Factor
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    ABSTRACT: Lymph node metastasis has a significant impact on laryngeal cancer prognosis. The role of lymph node ratio (LNR, ratio of metastatic to examined nodes) in the staging of laryngeal cancer was not reported. Records of laryngeal cancer patients with lymph node involvement from Surveillance, Epidemiology, and End Results database (SEER, training set, N = 1963) and Fudan University Shanghai Cancer Center (FDSCC, validating set, N = 27) were analyzed for the prognostic value of LNR. Kaplan-Meier survival estimates, the Log-rank χ(2) test and Cox proportional hazards model were used for univariate and multivariate analysis. Optimal LNR cutoff points were identified by X-tile. Optimal LNR cutoff points classified patients into three risk groups R1 (≤0.09), R2 (0.09-0.20) and R3 (>0.20), corresponding to 5-year cause-specific survival and overall survival in SEER patients of 55.1%, 40.2%, 28.8% and 43.1%, 31.5%, 21.8%, 2-year disease free survival and disease specific survival in FDSCC patients of 74.1%, 62.5%, 50.0%, and 67.7%, 43.2%, 25.0%, respectively. R3 stratified more high risk patients than N3 with the same survival rate, and R classification clearly separated N2 patients to 3 risk groups and N1 patients to 2 risk groups (R1-2 and R3). R classification is a significant prognostic factor of laryngeal cancer and should be used as a complementary staging system of N classification.
    PLoS ONE 01/2014; 9(1):e87037. · 3.53 Impact Factor
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    ABSTRACT: Five single nucleotide polymorphisms (SNPs) were previously reported to be associated with thyroid cancer in European populations in two genome-wide association studies (GWAS): rs965513 (9q22.33), rs944289 (14q13.3), rs116909374 (14q13.3), rs966423 (2q35) and rs2439302 (8p12). Only the first two SNPs have been validated in independent populations and none were replicated in Chinese populations. The above five SNPs were genotyped in 845 papillary thyroid cancer (PTC) and 503 benign thyroid tumour (BN) patients and 1005 controls in a Chinese population using the SNaPshot multiplex single nucleotide extension system. Significant associations were detected among PTC and rs944289 (p=8.007e-11), rs965513 (p=1.013e-4), rs966423 (p=1.688e-3) and rs2439302 (p=1.096e-4) in a dominant model, while the rs116909374 SNP was not detected in the Chinese population. The PTC risk increased with rise in accumulative numbers of risk alleles carried by individuals (p=5.929e-13). The PTC OR of carriers of six risk alleles (1.4% of the control population) was 23.587 compared with non-risk homozygotes (1.0% of the control population, with zero risk alleles). No individuals were homozygous for all the four SNPs (carriers of eight risk alleles) and only three PTC cases were carriers of seven risk alleles. A significant association between 14q13.3 SNP rs944289T and BN was also found (p=0.0014). Four candidate loci, rs965513 (9q22.33), rs944289 (14q13.3), rs966423 (2q35) and rs2439302 (8p12), identified by GWAS for PTC risk were confirmed in a Chinese population. The PTC risk of accumulative risk allele carriers increased with the number of risk alleles.
    Journal of Medical Genetics 07/2013; · 5.70 Impact Factor
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    ABSTRACT: Rs2910164, a Single nucleotide polymorphism (SNP) located in the precursor microRNA sequence of miR-146a, is the only MicroRNA sequence SNP studied in papillary thyroid cancer (PTC). Association studies had been performed in US and UK-Northern European populations, but results were inconsistence. This study evaluated the association between rs2910164 and the risk of PTC as well as benign thyroid tumor (BN), and examined the clinicopathological characteristics of PTC and BN for different genotypes. This case-control study genotyped rs2910164 in 753 PTCs, 484 BNs and 760 controls in a Chinese Han population. Clinicopathological and genetic data were collected and compared. Multivariate logistic regression was performed to calculate adjusted odds ratios (ORs). There were no differences in rs2910164 genotype distributions between the three groups. PTC cases with three genotypes (CC, CG, GG) had similar clinicopathological characteristics except the existence of "para-cancer" BN (PTC/BN, P = 0.006). PTC/BN patients were older (P = 0.009), and had smaller cancer lesions (<0.001), lower serum thyrotropin levels (1.82±1.42 . 2.21±1.74, 0.04), and lower rates of level VI lymph node metastasis (20.8% . 52.7%, <0.001) and lateral neck lymph node metastasis (11.5% . 23.0%, 0.011) compared with PTC only. Then we supposed a possible progression from BN to PTC which may involve rs2910164 in and performed a multivariate logistic regression analysis of PTC/BN and BN cases to determine risk factors of this progression. Results showed that the rs2910164 GG homozygote (OR = 2.25, 95% CI 1.22-4.14, P = 0.01) was the only risk factor in this study. Rs2910164 was not associated with increased risk of PTC and BN in Chinese patients, but may play a latent role in the transformation from BN to PTC.
    PLoS ONE 01/2013; 8(2):e56638. · 3.53 Impact Factor
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    ABSTRACT: BACKGROUND: The goal of this study was to identify the clinicopathological factors of co-existing papillary thyroid cancer (PTC) in patients with Hashimoto's thyroiditis (HT) and provide information to aid in the diagnosis of such patients. METHODS: This study included 6109 patients treated in a university-based tertiary care cancer hospital over a 3-year period. All of the patients were categorised based on their final diagnosis. Several clinicopathological factors, such as age, gender, nodular size, invasive status, central compartment lymph node metastasis (CLNM) and serum thyroid-stimulating hormone (TSH) level, were compared between the various groups of patients. RESULTS: There were 653 patients with a final diagnosis of HT. More PTC was found in those with HT (58.3%; 381 of 653) than those without HT (2416 of 5456; 44.3%; p < 0.05). The HT patients with co-occurring PTC were more likely to be younger, be female, have smaller nodules and have higher TSH levels than those without PTC. A multivariate analysis indicated that the presence of HT and higher TSH levels were risk factors for a diagnosis of PTC. In the PTC patients, the presence of HT or another benign nodule was a protective factor for CLNM, whereas no significant association was found for TSH levels. CONCLUSION: PTC and HT have a close relationship in this region of highly prevalent HT disease. Based on the results of our study, we hypothesise that long-term HT leads to elevated serum TSH, which is the real risk factor for thyroid cancer.
    BMC Cancer 12/2012; 12(1):610. · 3.33 Impact Factor
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    ABSTRACT: Chinese patients have a higher rate of lymphoepithelial carcinoma (LEC) and salivary duct carcinoma (SDC). Comprehensive use of diagnostic modalities, neck dissection, and postoperative radiation will improve the treatment results for salivary gland tumors (SGTs). To study the clinicopathological characteristics of SGTs in a Chinese population. The records of SGT patients operated in a tertiary cancer hospital of China were retrieved. From December 1997 to December 2007, 289 malignant and 887 benign SGTs were operated at Cancer Hospital, Shanghai, China. Pleomorphic adenoma and Warthin's tumor were the most common types of SGT. Mucoepidermoid carcinoma (24.6% of malignant cases) and adenoid cystic carcinoma (18.0%) were the most frequent malignant cases, followed by acinic cell carcinoma (12.1%), LEC (9.7%), and SDC (9.3%). The sensitivity and specificity of ultrasound scan, fine needle aspiration biopsy, and frozen section were 58.3 and 88.6%, 87.2 and 96.7%, 86.9 and 99.6%, respectively. Neck dissections and postoperative radiation were carried out for 48.6 and 48.0% of carcinomas, respectively. The percentage of tumors by pathologic TNM stage were 23.7% for stage I, 32.9% for stage II, 17.3% for stage III, and 26.1% for stage IV. The 5-year overall survival rate was 88.0%.
    Acta oto-laryngologica 04/2012; 132(8):879-86. · 0.98 Impact Factor
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    ABSTRACT: The surgical management of papillary thyroid microcarcinoma (PTMC), especially regarding the necessity of central lymph node dissection, remains controversial. The objective of the study was to describe the clinicopathological features of PTMC and to identify the risk factors for central lymph node metastasis (CLNM) that can guide surgical strategies for patients with PTMC. In this retrospective cross-sectional study, risk factors and outcome variables were assessed at the time of surgery for the primary tumor. The study was conducted at a university-based tertiary care cancer hospital. Data from the medical records of 1066 consecutive patients diagnosed with PTMC over a 5-yr period were analyzed. Our multivariate logistic regression analysis found male gender, younger age (≤45 yr of age), multifocal lesions, extrathyroidal extension, and larger size of the primary tumor (>6 mm) to be associated with CLNM; multifocal lesions were associated with the highest risk (odds ratio 4.476, 95% confidence interval 2.975-6.735). Extrathyroidal extension, multifocal lesions, and CLNM were associated with lateral neck lymph node metastasis (LLNM). In patients with a solitary primary tumor, tumor location in the upper third of the thyroid lobe was associated with a lower risk of CLNM and a higher risk of LLNM. Prophylactic central lymph node dissection need be considered in PTMC patients presenting with risk factors. In PTMC patients with a solitary primary tumor, tumor location can assist in the evaluation of LLNM. We recommend multicenter research and long-term follow-up to better understand the risk factors and surgical management of PTMC.
    The Journal of Clinical Endocrinology and Metabolism 02/2012; 97(4):1250-7. · 6.31 Impact Factor
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    ABSTRACT: To find the risk factors of lymph node (LN) metastasis of salivary gland cancer and draw a scheme for LN management. Hospital-based retrospective study. The records of salivary gland cancer patients treated at the Department of Head and Neck Surgery, Cancer Hospital, Fudan University, were entered in a database, and 219 consecutive patients with carcinomas of major salivary glands primarily operated on between January 1998 and January 2011 were chosen for univariate and multivariate analysis to identify risk factors for LN involvement. Fifty-eight (26.5%) patients had LN involvement. Factors associated with cervical LN involvement on univariate analysis included pathologic type, male sex, shorter duration of preoperative course, facial paralysis, advanced T stage, and major nerve, soft tissue, lymphatic/vascular (L/V), neural/perineural, and extracapsular invasion. Multivariate analysis identified major nerve invasion, histologic type, L/V invasion, and extracapsular invasion as significant factors for LN involvement. The proportion of patients with LN involvement with low (105), middle (61), high (34), and super high (19) predictive index scores based on the four risk factors were 3.8%, 27.9%, 55.9%, and 94.7%, respectively. A predictive index using the clinicopathologic factors described in this report can effectively stratify patients into risk groups for nodal metastasis. Comprehensive management based on this risk index should improve treatment outcomes for patients with salivary gland cancer.
    The Laryngoscope 02/2012; 122(7):1497-506. · 1.98 Impact Factor
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    ABSTRACT: There exists no universally accepted treatment for primary thyroid non-Hodgkin's lymphoma (TNHL) due to the rarity of this entity. The aim of this study is to assess the role of surgery and to explore prognostic factors in Chinese TNHL patients. Patient presentations, pathologies, surgical interventions, multidisciplinary treatment, prognostic factors and the value of fine needle aspiration were analyzed. Between 1991 and 2007, 40 patients of TNHL were diagnosed. Thirty-eight patients underwent an initial surgical procedure. Further treatments consisted of radiotherapy or chemotherapy alone, and the majority of patients were treated with combined chemo-radiation. After a median follow-up of 95 months, the 5-year overall survival (OS) and relapse-free survival (RFS) was 82% and 74%, respectively. Survival curves showed no significant difference between therapeutic operations when compared with diagnostic operations. A univariate analysis showed both International Prognostic Index (IPI) and staging significantly influenced OS and RFS. In multivariate analysis, IPI was found to be the only prognostic factor. Combined chemotherapy and radiotherapy may offer better outcome without the need for extensive resection, and surgery should be reserved to providing tissue for diagnosis. The patients with low-intermediate risk (IPI = 2) or stage IIE need be treated more aggressively.
    Journal of Surgical Oncology 06/2010; 101(7):545-50. · 2.64 Impact Factor
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    ABSTRACT: To assess the significance of central compartment dissection in papillary thyroid cancer with negative clinical lymph node metastasis. Clinical and pathological data of 641 papillary thyroid cancer patients with negative clinical lymph node metastasis who were treated from January 1998 to April 2006 were collected. The positive rate of the lymph nodes metastasis was analyzed. The relations between the central compartment lymph nodes and the patients' gender, age, tumor size and number were concerned. Among the 641 cases, 114 case who received operation more than five years were followed up for the relations between the pathological status of central compartment lymph nodes and ipsilateral neck metastasis or contra thyroid lobe recurrence. The median number of the central compartment lymph nodes was 4 each case and 53.0% (340/641) cases of papillary thyroid cancer patients with negative clinical lymph node metastasis had positive central compartment lymph nodes metastasis. Large tumor size and multiple origins were related to central compartment lymph nodes involvement, but the patients' gender or age was not. In the 114 follow-up cases, ipsilateral neck metastasis occurred in 12 cases, among which 11 cases had high positive central compartment lymph nodes metastasis. Contra thyroid lobe recurrence occurred in 5 cases, whose statuses of central compartment lymph nodes were different. Papillary thyroid cancer patients with negative clinical lymph node metastasis deserve formal central compartment dissection. The pathological status of central compartment lymph nodes relates to the tumor size and number. High positive rate of central compartment lymph nodes may lead to possible ipsilateral neck metastasis.
    Zhonghua wai ke za zhi [Chinese journal of surgery] 05/2007; 45(7):470-2.
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    ABSTRACT: To analyze the somatic mutations in the D-loop of mtDNA and further evaluate the possibility of mitochondrial genetic instability in thyroid papillary carcinoma. Hypervariable regions ( HVR-I and HVR-II) in the D-loop of mtDNA from the specimen of 35 thyroid papillary cancers and matched lymphocytes were amplified by PCR, and then were sequenced. Comparing the sequences of tumors to those of matched lymphocytes and normal thyroid tissues, 5 somatic mutations in 2 patients (5.7%) were found. Two mutations were insertions of C in a poly-cytidine (nt303) microsatellite, and 3 at positions 73, 152 and 194 in HVR-II. In addition, of the 294 genetic variants detected, 292 were previously recorded polymorphisms, whereas 2 were new polymorphisms (nt324:C-->G, nt16092:T-->A). Mutations in the D-loop of mtDNA were found in thyroid papillary cancers, this mutation rate was lower than the reported rate of alteration in tumors of epithelial origin, and further work is required to elucidate the relationship between this mutations and the development of thyroid papillary carcinoma.
    Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery 10/2006; 41(10):782-5.
  • Hong-shi Wang, Zhuo-ying Wang, Duan-shu Li
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    ABSTRACT: To avoid hoarseness for operation of schwannoma of the cervical vagus nerve (SVN). From Jan. 1997 to Sept. 2001, ten cases of SVN were operated. The procedures were as follows: Exposing the tumor and the vagus nerve, confirming its origin from the fascicle of recurrent laryngeal nerve (RLN) or the fascicle of non-RLN, making an small incision on the posterolateral surface of the tumor, usually posterior to the internal jugular vein, and then tearing and enlarging the small incision to enucleate the tumor. Two of the four cases of SVN originated from the fascicle of RLN happened temporary hoarseness and other two without hoarseness. All six cases of SVN originated from the fascicle of non-RLN, but one, happened no hoarseness. Above-mentioned technique is a good and reliable method to avoid hoarseness in the operation of SVN.
    Zhonghua er bi yan hou ke za zhi 03/2003; 38(1):57-9.