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Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.
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Objective:To evaluate preoperative serum ferritin (SF) in predicting the prognosis of patients with esophageal squamous cell carcinoma (ESCC).Methods:A retrospective analysis was conducted on 280 ESCC patients undergoing radical resection of esophageal cancer at Zhejiang Cancer Hospital from Jan 2008 to Dec 2013. Univariate and multivariate analysis were used to investigate the relationship between preoperative SF level and patients′ clinicopathologic characteristics. Kaplain-Meier method was used to analyze the relationship between preoperative SF level and the prognosis.Results:There were 183 cases (65.4%) with low SF level and 97cases (34.6%) with high SF level. The 1-, 3-and 5-year survival rates in low SF patients were 78.7%, 50.3%, 43.2% and that in high SF were 69.1%, 35.1%, 32.0%, respectively (χ 2=4.697, P=0.031). Univariate analysis demonstrated that intravascular cancer embolus, nerve infiltration and the level of preoperative SF were related to ESCC patients prognosis (all P<0.05). The multivariate analysis showed that carcinoma cell embolus ( OR=1.662, 95% CI: 1.239-2.229, P=0.001), nerve infiltration ( OR=1.823, 95% CI: 1.361-2.443, P<0.001) and the level of preoperative SF ( OR=1.504, 95% CI: 1.113-2.032, P=0.008) were independent risk factors for ESCC patients prognosis. Conclusion:Preoperative SF level closely associates with the prognosis of ESCC patients.
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Objective To investigate the clinical features and prognostic characteristics of head and neck cancer in patients with esophagus cancer and triple primary carcinoma(TPC).Methods A total of 30 patients with head and neck cancer with esophagus cancer TPC were collected in Zhejiang Cancer Hospital from January 2007 to December 2016.The distribution of cancer kinds and the incidence of synchronous and metachronous cancer were described.The clinical characteristics and prognosis were also compared in synchronous and metachronous cancer.The influence of number of hospitalization and different treatments on the survival time were analyzed.Results The TPC of "laryngeal pharynx + esophagus + lung" and "laryngeal pharynx + esophagus + oropharynx" had the highest incidence,that was 20.0％ in 30 patients (6/30).The second type was "laryngeal pharynx + esophagus + larynx".Fifteen cases were synchronous cancer and other 15 cases were metachronous cancer.The rate of surgery was 73.3％ (11/15),and the number of hospitalization who more or equal than 5 was 73.3％ (11/15) in the synchronous cancer.While the rate of surgery was 33.3％ (5/15),and the number of hospitalization who more or equal than 5 was 33.3％ (5/15) in the metachronous cancer.There were significant differences between synchronous and metachronous cancer (x2 =4.661,4.661,all P ＜ 0.05).The 1-year,3-year and 5-year survival rates were 39.9％,19.9％ and 0.0％ in patients with synchronous cancer.The mean survival time was (18.4 ± 6.2)months.In contrast,the survival rates were 78.7％,77.8％ and 59.1％ in metachronous cancer.The mean survival time was (122.2 ± 17.2) months.There were significant differences between the two groups (survival rate:x2 =10.934,P =0.001;mean survival time:t =3.201,P =0.003).The survival rate of the number of hospitalization more than or equal to 5 times had significant difference compared with those less than 5 times (x2 =10.574,P =0.001).There was no statistically significant difference in the improvement of OS between single operation,chemotherapy and target treatment (P ＞ 0.05).Conclusion Head and neck cancer in patients with esophagus cancer TPC can still has a high survival rate through active combined modality therapies,especially in metachronous carcinoma.
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Objective To evaluate the clinical efficacy of prophylactic cranial irradiation (PCI) in the treatment of surgically resected small cell lung cancer (SCLC).Methods Clinical data of SCLC patients undergoing radical resection surgery in Zhejiang Cancer Hospital from 2003 to 2015 were retrospectively analyzed.According to the treatment modality,all patients were allocated into the PCI and non-PCI groups.A total of 52 patients were finally included,including 19 patients in the PCI group (5 cases of stage Ⅰ,5 stage Ⅱ and 9 stage Ⅲ) and 33 in the non-PCI group (12 cases of stage Ⅰ,5 stage Ⅱ and 16 stage Ⅲ).Kaplan-Meier method was utilized for survival analysis.Cox proportional hazards model was adopted to analyze clinical prognosis.Results The median survival time was 32.9 months in the PCI group,and 20.4 months in the non-PCI group.The 2-year overall survival rate was 72％ in the PCI group,significantly higher than 38％ in the non-PCI group (P=0.023).The median brain metastasis-free survival (BMFS) was 32.5 months in the PCI group,and 17.1 months in the non-PCI group.In the PCI group,the 2-year BMFS rate was 89％,significantly better than 53％ in the non-PCI group (P=0.026).Subgroup analysis demonstrated that PCI could confer survival benefit to patients with p-stage Ⅲ (p=0.031) rather than p-stage Ⅰ (P=0.924) and Ⅱ (P=0.094) counterparts.Multivariate analysis revealed that PCI (HR=0.330,P=0.041) was an independent prognostic factor of the overall survival.Conclusions PCI can reduce thr risk of brain metastasis rate and improve the overall survival of patients with surgically resected SCLC.
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Objective To compare the efficacy of trimodality therapy and chemoradiation therapy (CRT) alone in patients with locally advanced resectable esophageal squamous cell carcinoma (SCC).Methods A total of 124 cases with locally advanced resectable esophageal SCC were retrospectively analyzed and classified into 2 groups.Fifty-four cases in trimodality group were treated with surgery and preoperative chemoradiation,while 70 cases in CRT alone group only received radiation and chemotherapy.Local tumor control,3-year survival and treatment-related mortality were assessed.Results The local recurrent rate of the resected patients was 18.5％ in trimodality group and 35.7％ in CRT alone group,respectively(x2 =4.445,P ＜ 0.05).The 3-year progression-free survival (PFS) was 65.3％ (95％ CI 50.7-80.5) in trimodality group and31.9％ (95％CI 19.6-44.2) in CRT alone group (P＜0.05),while the overall survival (OS) 66.3％ (95％ CI43.0-89.6) and 34.4％ (95％ CI 21.1-47.7),respectively(P ＜ 0.05).Treatment-related mortality was 1.9％ in trimodality group and 2.9％ in CRT alone group (P ＞ 0.05).For CRT alone group,the sub-group analysis showed that there was no statistically significant difference in the 3-year OS between patients who received 50-50.4 Gy and those who received the dose over 50.4 Gy (39.9％ 95％ CI 18.5-61.3 vs.31.5％ 95％ CI 14.8-48.2,P ＞0.05).Conclusions Compared with CRT alone,trimodality therapy showed the superior local control,PFS and OS,with similar treatment-related mortality in the treatment of patients with SCC of esophagus.The role of surgery could not be replaced by CRT alone even with the augment of radiation dose.
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Malignant mesothelioma(MM) is a rare but highly invasive carcinoma associated with asbestos exposure.Its incidence is in rising trend and most cases occur in pleura and peritoneum.The majority of patients diagnosed at late stage with poor prognosis that the median overall survival is only 12 months.Accurate diagnosis depends on the histopathology combined with immunohistochemistry.At present, the treatment of MM is mainly based on the tumor reduction or resection surgery combined with chemotherapy and radiotherapy.The potential molecular target needs to be further investigated.In this paper, we summary the incidence, diagnosis and treatment of MM, which will benefit the diagnosis and treatment of MM in China.
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Objective The survival and prognosis factors of thoracic esophageal squamous cell carcinoma patients after radical resection was investigated.Methods 1923 patients of thoracic esophageal squamous cell carcinoma after radical resection were included in our study from January 1th 2000 to January 1th 2010 in Zhejiang Cancer Hospital,1 670 male and 253 female.the age in the majority with 40 to 59 years old(1 076/1 923,56.0％).Eighteen prognosis factors were collected.A multivariate analysis of these selected variables was performed using Cox proportional model and prognosis index.We used life table for accumulated survival rate.Results The accumulated survival rate for all patients were 82％,48％ and 35％ in 1 year,3 years and 5 years,respectively.Median survival time was 35.42 months.The significant prognosis factors included body mass index,length of tumor,depth of invasion,differentiation degree,lymph node metastatic degree and region,complication of surgery.Conclusion The prognosis of thoracic esophageal squamous cell carcinoma was affected by multi-factors and prognosis index can predict survival condition.
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Objective@#To investigate the expression of BRCA-associated protein 1 (BAP1) in malignant mesothelioma, non-small cell lung cancer and carcinosarcoma, and its application in the differential diagnosis.@*Methods@#Twenty-two cases of malignant mesothelioma including 17 epithelioid type, 2 sarcomatoid type and 3 biphasic type were collected.As the study control, 80 non-small cell lung cancers infringement pleural membrane(including 40 lung adenocarcinomas and 40 lung squamous cell carcinomas) and 15 carcinosarcomas were included. BAP1 expression was detected using immunohistochemical method. A differential diagnosis antibody panel, including calretinin, WT1, CK5/6, D2-40, CAM5.2, CEA, TTF1, Napsin A, p63 and p40 was tested in all cases.@*Results@#All 80 cases of non-small cell lung cancer and 15 cases of carcinosarcoma were BAP1 positive. In contrast, 64% (14/22) of malignant mesotheliomas lost BAP1 expression (P<0.01). Addition of BAP1 to the mesothelioma marker panel, the diagnostic accuracy of malignant mesothelioma was enhanced to 93%. Focal expression of BAP1 in tumors suggested multiclonal evolution of mesothelioma.@*Conclusions@#Loss of BAP1 expression helps to confirm the diagnosis of malignant mesothelioma whereas all non-small cell lung cancer expresses BAP1. It is therefore recommended that BAP1 can be used in conjunction with other immunohistochemical markers to improve the diagnostic accuracy of malignant mesothelioma.
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Objective To evaluate the diagnostic value of ultrasound-guided fine needle aspiration cytology(US-FNAC)in the assessment of radiologically detected ovarian neoplasms and retroperitoneal metastatic lymph nodes. Methods FNAC was performed under ultrasound guidance on 126 patients suspected of ovarian neoplasms and retroperitoneal metastatic lymph nodes. Cytologic examination was performed after staining smears with the haematoxylin and eosin method. Clinical data were retrieved from the medical records and all cytological specimens were reviewed. In these cases, the cytologic findings were correlated with histology of the primary tumor and were compared with surgical pathology. Results Satisfactory sampling was obtained in 86.2% of punctures, and cytological diagnosis was made in 85.7% cases. The size of the lymph nodes punctured was less than 20 mm in 93.5% cases, with the sensitivity of 81.6%、86.2%, specificity of 95.8%、100.0%, positive predictive value of 98.3%、100.0%, negative predictive value of 63.9%、33.3%, and accuracy of 85.3%、87.1%. Seven patients presented slight abdominal discomfort, and relieved without clinical treatment. Conclusions The fine needle aspiration technique has excellent positive predictive value and low morbidity. US-FNAC, as the valuable investigation, is not only useful in the diagnosis of ovarian masses and lymph nodes but can also help in choosing appropriate management. From our experience, US-FNAC can be added in follow-up of selected patients in whom the cytological identification of such masses and nodes is significant for the patient′s treatment.
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Objective:To analyze the characteristics of regional lymph node metastasis in patients with resectable non-small cell lung cancer (NSCLC) and assess its clinical significance in surgical mediastinal lymph dissection and the target volume definition of postoperative radiotherapy. Methods:We retrospectively reviewed 810 patients with NSCLC, and analyzed the metastatic frequency of each regional lymph node station as well as the correlation between tumor location and regional lymph node metastases. Results:Re-gional lymph node metastases were significantly associated with the age of patients, histology, tumor size, and tumor location (P=0.013, 0.000, 0.009 and 0.000, respectively). Conclusion:The younger patients with left lung adenocarcinomas and large tumor size tended to regional lymph node metastases. The trend of regional lymphatic drainage in the lobes of lung occurred differently. The prior location of involved regional lymph nodes in different lobes of the NSCLC patients was as follows:The station 2-4 for right upper lobe tumors, the station 2-4 and 7 for right middle lobe tumors and right lower lobe tumors, the station 5-6 for left upper lobe tumors, and the station 5-6 and 7 for left lower lobe tumors. We should pay more attention to the regions regarding the higher frequencies of lymph node metastases, when determining the extent of lymph node dissection or delineating the target volume of postoperative radiotherapy for NSCLC patients.
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Esophageal cancer is a cause of cancer mortality and accounts for the sixth most common cause of cancer-related death. The focus of recent study has shifted towards testing novel agents that target specific molecular abnormalities known to occur in esophageal squamous cell carcinoma (ESCC). The preclinical studies involving various cancer models, including ESCC, epidermal growth factor receptor (EGFR) over-expression, are linked to epithelial cell proliferation, differentiation and migration, and have an inverse relationship to tumor chemotherapy curability. Nimotuzumab is a humanized anti-EGFR monoclonal antibody that binds to the extracellular domain of the EGFR and inhibits EGF binding. In many phase Ⅱ trials, nimotuzumab showed marked antiproliferative, proapoptotic and antiangiogenic effects in tumors that overexpress EGFR. Some phaseⅢtrials are ongoing.
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Objective To investigate the incidence and mortality of brain tumor in Zhejiang cancer registration areas from 2000 to 2009.Methods Data from 6 Cancer registration areas of Zhejiang province were collected.Number of cases,crude rates,proportions,age standardized rates,cumulate rates,cut rates,age-specific rates and annual percentage change (APC,95％ CI) of brain tumor incidence and mortality were analyzed.Results There were 5 123 new diagnosed brain tumor cases in Zhejiang cancer registration areas,accounting for 3.14％ of all the new cancer cases.The incidence rate of brain tumor was 8.53/100 000,and the standardized incidence rate by Chinese population was 5.72/100 000,ranking the 7th in cancer incidence spectrum of anatomic sites.Agespecific incidence of brain tumor increased along with age,and peaked among 70-74 age groups (24.09/100 000).The annual incidence rate of brain tumor increased from 2000 (6.87/100 000) to 2009 (8.35/ 100 000),with APC as 1.58％ (95 ％ CI:-2.17％-5.47％,no statistical significance).A total of 2 357 deaths caused by brain tunor were reported from 2000-2009,accounting for 2.47％ of all the cancer death cases.Mortality rate on brain tumor appeared to be 3.92/100 000,with the standardized mortality rate by Chinese population as 2.45/100 000,ranking the 7th in cancer mortality spectrum of anatomic sites.The age-specific mortality of brain tumor remained low among 0-39 year-olds,and reached the peak at 80-84 age groups (17.64/100 000).The annual mortality rate of brain tumor decreased from 2000 (4.30/100 000) to 2009 (3.83/100 000) with minor fluctuation,and the APC was-0.65％ (95％CI:-3.35％-2.12％,no statistical significance).Conclusion Brain tumors incidence and mortality in Zhejiang cancer registration areas were at a relatively high level.People who were at middle-age,especially above 70 years old should be the key targets for protection on this disease.Brain tumor incidence rates increased annually in Zhejiang,which should be called for attention.
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Objective To investigate the epidemic characteristics and trends of incidence and mortality of prostate cancer in cancer registration areas in Zhejiang province from 2000 to 2009.Methods Clinical data incidence and mortality of prostate cancer were collected from 6 cancer registration areas in Zhejiang province,including Hangzhou,Jiaxing,Jiashan,Haining,Shangyu and Xianju.Crude rates,standardized rate and change trend,age-specific rates and annual percent change (APC,95％ CI) of prostate cancer were checked,sorted and analyzed in Zhejiang Cancer Center.Results The prostate cancer incidence rate from 2000 to 2009 was 9.79/100 000,age-standardized incidence rates by world standard population (ASIRW) was 6.39/100 000,and the incidence cumulative risk of males aged 0-74 was 0.72％ ; while the mortality rate was 2.73/100 000,age-standardized mortality rates by world standard population was 1.74/100 000,and the mortality cumulative risk of males aged 0-74 was 0.14％.Age-specific incidence of prostate cancer remained low before 50,years old and peaked at over 85-year-old group (130.30/100 000).Age-specific mortality of prostate cancer increased after 55,and also peaked at over 85-year-old group (81.19/100 000).The annual prostate cancer incidence rate generally grew from 1.39/100 000 (2000) to 13.89/100 000 (2009),and the APC was 14.18％ (95％ CI,9.68％-18.98％).Meanwhile,the prostate cancer mortality rate also increased from 1.52/100 000 (2000) to 3.58/100 000 (2009),and the APC was 11.83％ (95％ CI,5.69％-18.33％).Conclusion Prostate cancer incidence and mortality in Zhejiang cancer registration areas increased sharply,and the prevention and treatment of prostate cancer should be strengthened.
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Background and purpose:The prognostic role of human epidermal growth factor receptor 2 (HER-2) remains controversial in patients with non-small cell lung cancer (NSCLC). This study aimed to evaluate the expression of HER-2 and its prognostic implication in patients with NSCLC.Methods:Four hundred and twenty-ifve NSCLC patients’ specimens were obtained from Zhejiang Cancer Hospital. HER-2 protein expression was determined by immunohistochemistry (IHC). The relationship between HER-2 and clinicopathological parameters and patients’ prognosis was analyzed by Chi-square test and COX proportional hazards regression model.Results:Eighty-three patients were positive expression of HER-2 (83/425, 19.5%). The expression of HER-2 was closely related with histological type (P=0.051), most patients with HER-2 positive were adenocarcinoma, then were squamous carcinoma or other histological types. However, HER-2 was not an independent prognostic indicator for the overall survival of patients with NSCLC.Conclusion:We found that the expression of HER-2 was closely connected with histological type, but it was not a predictive marker for the prognosis in patients with NSCLC.
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Lymph nodes (LN)are the main parts of the esophageal cancer metastasis,and the current status of LN is the important indicator of prognosis.LN metastasis appears in early stage of esophageal cancer.One side,LN metastasis easily appears in the regions near the tumor and some special areas.On the other side,LN metastasis has the characteristics of wide metastasis and skip metastasis.Therefore,the researches of the pattern of esophageal cancer lymph node metastasis can help to comform the scope of the esophageal cancer lymph node dissection and the target regions of radiotherapy.
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<p><b>OBJECTIVE</b>To investigate the incidence and mortality rates of thyroid cancer in Zhejiang province during 2000 to 2009.</p><p><b>METHODS</b>The data of thyroid cancer were collected from six cancer registries in Zhejiang province and the incidence and mortality rates of thyroid cancer were analysed.</p><p><b>RESULTS</b>The mean annual incidence rate of thyroid cancer in Zhejiang cancer registration areas was 6.93/100 000 during 2000 to 2009, and male/female ratio was 1: 3.43. The incidence rate was 3.62/100 000 in 2000 and it increased to 11.42/100 000 in 2009, with the annual percent change (APC) of 16.32% (95% confidence interval: 12.90%-19.85%). The mean annual mortality rate of thyroid cancer was 0.27/100 000 during 2000 to 2009, and male/female ratio was 1: 1.12. The mortality showed a rising trend without a distinct fluctuation from 2000 to 2009, the APC was 2.14% (95% confidence interval: from -7.10% to 12.30%). The incidence showed a rising trend with the increase of ages after 15 years old, and peaked at 55-60 years old. The mortality was low before 54 years old, but showed a rising trend with a distinct fluctuation after 55 years old, and peaked at 85-90 years old.</p><p><b>CONCLUSION</b>The prevention and control of risk factors for thyroid cancer in young and middle-aged people is key to decrease the incidence and mortality of thyroid cancer.</p>
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Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Young Adult , Age Factors , China , Epidemiology , Incidence , Prevalence , Registries , Sex Factors , Thyroid Neoplasms , Epidemiology , MortalityABSTRACT
Objective To detect the expressions of microRNA-126 (miR-126) and microRNA-7 (miR-7) in esophageal squamous cell carcinoma (ESCC) and to analyze their correlations with clinicopathologic features and prognosis of ESCC.Methods The expressions of miR-126 and miR-7 in 116 ESCC samples and matched normal tissue samples were detected by real-time PCR.Statistical analysis was used to find the relationships among the expressions of miR-126 and miR-7,pathological characteristics and prognosis.Results Low expression,normal expression and high expression of miR-126 were found in 73 (62.9％),35 (30.2％) and 8 (6.9％) carcinoma samples respectively.Low expression,normal expression and high expression of miR-7 were found in 52 (44.8％),35 (30.2％) and 29 (25.0％) carcinoma samples respectively.The disease-free survival in patients with low expression of miR-126 and miR-7 was shorter than that in patients with non-low expression (x2 =4.268,P ＜0.05 ; x2 =4.993,P ＜0.05).The low expression of miR-126 was correlated with tumor location,family history and drinking (x2 =14.564,P ＜ 0.05 ; x2 =5.691,P ＜ 0.05 ; x2 =4.971,P ＜ 0.05),but was uncorrelated with gender,age,diferentiation,infiltration,lymphatic metastasis and smoking (all P ＞ 0.05).The low expression of miR-7 was uncorrelated with pathological characteristics of ESCC (all P ＞ 0.05).Conclusion The low expressions of miR-126 and miR-7 may be related to the prognosis of patients with ESCC,and have a certain clinical detection significance.
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Background and purpose:It was reported that many microRNAs (miRNAs) have close relation with carcinomas. miR-31 (microRNA-31) shows abnormal change in numerous cancers. China is one of the most high-risk areas of esophageal squamous cell carcinoma (ESCC). The aim of the present study was to investigate the expression of miR-31 in ESCC, and analyze the relationship of its expression with clinicopathological features and prognosis. Methods:The expression of miR-31 in KYSE410, EC1 and EC9706 cell lines, as well as 81 cases of ESCC tissues and adjacent normal esophageal tissues were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR). The result was combined with clinical and follow-up data and statistical analysis was conducted. Results: MiR-31 was up-expression in 3 cell lines and 75.31% of the ESCC tissues. miR-31 up-expression was positively related to severer lymph node metastasis (P=0.043), deeper invasion of tumors (P=0.002) and advanced pathological stage (P=0.027). There was no relationship of miR-31 with other clinicopathological features (P>0.05). Furthermore, high expression of miR-31 was associated with poor progression-free survival (PFS) in 81 ESCC patients by Kaplan-Meier analysis (P=0.014) and by multivariate Cox analysis (P=0.021). Conclusion:Our results identiifed miR-31 may be a new diagnostic criteria and prognostic biomarker for ESCC.
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With depth understanding of the mechanism of human leukocyte antigen G (HLA-G) protein,more and more studies have found that HLA-G is closely related with tumor immune escape.Numerous studies have shown that the expression of HLA-G protein and mRNA could be detected in patients with cancer.
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ObjectiveTo investigate the methylation status of multiple genes in plasma and tumor tissues and its application in molecular diagnosis of esophageal squamous cell carcinoma (ESCC).Methods Methylation specific polymerase chain reaction (MSP) was used to detect methylation status of 5 tumor suppressor genes,such as adenomatous polyposis coli ( APC ),retinoic acid receptor-beta2 ( RARβ2 ),E-cadherin (CDH1),cyclin-dependent kinase inhibitor4A (p16INK4α) and ras association domain family member 1 A (RASSF1A) in tumour tissues,adjacent normal tissues and plasma which obtained 1 d preoperative and 7 d postoperative in 76 cases with ESCC.60 healthy volunteers were randomly selected as a control which were age-matched and sex-matched.Chi square test was used to analyze DNA methylation rates of 5 genes in various groups of tissue and plasma samples; Kappa test was used to compare the consistency of DNA methylation in the plasma samples and tissue samples,and their correlation was analyzed by Spearman correlation test; Receiver operating characteristic curve (ROC) was used to evaluate the sensitivity and specificity for single gene detection and 5 genes joint detection for diagnosis of esophageal squamous cell carcinoma.ResultsThe methylation rates of APC,RARβ2,CDH1,p16INK4α and RASSF1A in tumour tissues of patients with ESCC were 44.7％ ( 34/76),72.4％ ( 55/76 ),72.4％ (55/76),86.8％ ( 66/76 ),55.3％ (42/76),respectively,which were significantly higher than that in the corresponding adjacent normal tissues [ 6.6％ ( 5/76 ),3.9％ ( 3/76 ),3.9％ ( 3/76 ),3.9％ ( 3/76 ),2.6％ ( 2/76 ),x2 =29.01,75.39,75.39,105.34,57.18,all P ＜ 0.001 ].The methylation rates of above 5 genes in patients' plasma were 42.1％ ( 32/76 ),63.2％ ( 48/76 ),63.2％ ( 48/76 ),71.1％ ( 54/76 ),50.0％ ( 38/76 ),respectively,which were significantly higher than that of control group [3.3％ (2/60),3.3％ (2/60),1.7％ ( 1/60),3.3％ (2/60),1.7％ (1/60),x2 =26.88,51.62,55.01,63.48,38.30,all P ＜ 0.001 ].The methylation consistency was favorable or well between plasma and tumour tissues in patients with ESCC ( Kappa value was 0.679,0.791,0.791,0.542 and 0.895,respectively.all P ＜0.001 ).In single-gene detection for patients' plasma,methylation,the sensitivity of 5 genes was 42.1％ ( 32/76 ),63.2％ ( 48/76 ),63.2％ ( 48/76 ),71.1％ ( 54/76 ),50.0％ ( 38/76 ),respectively.The specificity was 96.7％ ( 58/60 ),96.7％ ( 58/60 ),98.3％ (59/60),96.7％ (58/60),98.3％ (59/60),respectively.The area under curve (AUC) of ROC was 0.694 [95％ confidence interval( CI)0.606 - 0.782 ) ],0.799 ( 95％ CI 0.723 - 0.875 ),0.807 ( 95％CI 0.733 - 0.882),0.839 ( 95 ％ CI 0.769 - 0.908 ) and 0.742 ( 95 ％ CI 0.659 - 0.824 ),respectively.In united testing of 5 genes,the sensitivity was 80.3％ and the specificity was 88.3％,AUC was 0.843 (95％CI 0.773 -0.913 ).The sensitivity of united testing was significantly higher than that of single-gene detection of APC and RASSF1A(x2 =23.30,15.33 ; P ＜ 0.001 ),except RARβ2,CDH1 and p16INK4α (x2 =5.48,5.48,1.75; P =0.019,0.019,0.186);There was no significant differences in specificity between united testing and single-gene detection (x2 =1.922,1.922,3.348,1.922,3.348,all P ＞ 0.05 ).Conclusions The methylation consistency is favorable or well between tumour tissues and plasma in patients with ESCC.There is no significant superior in diagnosing ESCC with united testing of multiple tumor suppressor genes methylation in plasma than with single-gene detection.But the sensitivity of the former is better than the latter.