Objective:To analyze the expression of mismatch repair (MMR) proteins in colorectal cancers (CRC) and to evaluate the feasibility and potential pitfalls of immunohistochemistry (IHC) analysis for MMR.Methods:The IHC sections for MMR proteins were reviewed in 3 428 cases of resected CRC without neoadjuvant therapy at Tianjin Medical University Cancer Institute and Hospital from July 2014 to October 2018. For the cases with unclear MMR IHC results during the initial review, IHC staining was repeated and microsatellite instability (MSI) analysis was performed. Relationships between the expression of MMR proteins and MSI status as well as the clinicopathological parameters were analyzed.Results:IHC staining for MMR was repeated in 28 (0.8%) cases due to poor quality of original IHC sections. Inconsistent results between the original diagnosis and re-diagnosis were found in 119 (3.5%) cases, mainly resulting from PMS2 and MLH1. Finally, 261 (7.6%) cases of CRC showed mismatch repair deficiency (dMMR), mainly from the deficiency of both MLH1 and PMS2 (43.3%,113/261). In the 14 cases with MSI results, the concordant of MSI and MMR was 13 cases. In the 29 dMMR cases with next generation sequencing (NGS) results, the concordant of MSI-high and dMMR was 93.1%(27/29). The cases with inconsistent results between MSI and MMR showed negative expression of MSH6 or PMS2. Twenty-one CRC showed negative expression of MLH1 and partially positive (or weak positive) expression of PMS2, or negative expression of MSH2 and partially positive (or weak positive) expression of MSH6. Among the 19 cases with MSI results, 16 cases were MSI-high, two cases were MSI-low, and one case was microsatellite stable. Compared with mismatch repair proficiency (pMMR), dMMR was more frequently detected in female patients younger than 50 years old, with family history, at early stage (Ⅰ-Ⅱ) CRC, and in the tumors from right colon,with poor differentiation, or mucinous adenocarcinoma/signet ring cell carcinoma (all P<0.05). Conclusions:At present, IHC staining is a clinically effective and convenient method to detect MMR expression, but the operating process and result assessment remain variable and need to be standardized. MSI analysis can be performed in the difficult-to-evaluate cases for MMR to enhance prognostic evaluation and treatment option.

Xp11 translocation renal cell carcinoma is a rare renal cell carcinoma subtype harboring a TFE3 translocation, which is grouped into the MiT family translocation renal cell carcinomas together with t (6;11) translocation renal cell carcinomas. With the de-velopment and application of immunohistochemistry, fluorescence in situ hybridization, reverse transcription-polymerase chain reac-tion, and RNA sequencing, increasingly more Xp11 translocation renal cell carcinomas have been diagnosed and studied, and many new insights have been elucidated and advances have been made in clinicopathology, molecular genetics, and clinical treatment. The latest progress in Xp11 translocation renal cell carcinoma research is introduced and reviewed in this paper.

Objective: To detect the expression of SVEP1, PKHD1 and P53 in primary liver cancer tissues by immunohistochemistry for predicting the recurrence of liver cancer. Methods: The clinical data of 103 patients with primary liver cancer who underwent surgical resection at Tianjin Medical University Cancer Institute and Hospital were gathered from January 2013 to January 2014 and analyzed retrospectively. Expression values of three different proteins were used to develop separate immunohistochemical scores for the prog-nosis of recurrence in patients. The patients were classified into either a high-risk or a low-risk group based on their immunohisto-chemical scores through ROC curve analysis. The difference in recurrence ratio between the two groups was then compared using the common research index of disease-free survival (DFS). Results: The median age of the total patients was 55 years (range 21-88 years), the median AFP level was 70.6 (range 1.03-718840.0) μg/L, the median CA19-9 level was 22.89 (range 0.6-1000.0) kU/L, and the medi-an tumor size was 4.5 (1.0-27.0) cm. The expression levels of SVEP1, PKHD1, and P53 in primary liver tumors were detected by immu-nohistochemistry and assigned separate immunohistochemical scores. The areas under the ROC curves of the immunohistochemical scores of SVEP1, PKHD1, and P53 were 0.861, 0.829, and 0.716, respectively. The critical values of SVEP1, PKHD1, and P53 were 4, 4, and 1 point, respectively (P<0.001). The three-year DFS rates among the SVEP1 high-risk (expression≤4 points) and low-risk groups (expression>4 points) were 4.1% and 51.7%, respectively. Similarly, the three-year survival rates among the PKHD1 high-risk (expres-sion≤4 points) and low-risk groups (expression>4 points) were 5.3% and 51.9%, respectively. The three-year DFS rates among the P53 high-risk (expression>1 point) and the low-risk group (expression≤1 point) were 6.3% and 27.3%, respectively. The survival differenc-es between all the pairs were statistically significant (P<0.001,<0.001, and 0.003 respectively). When PKHD1 was used in combination with SVEP1, the ROC curve had an area of 0.897 (P<0.001) with a sensitivity of 76.5% and a specificity of 94.4%. Conclusions: The accu-racy of P53 data for predicting primary liver cancer recurrence is insufficient and therefore it is not recommended for use. SVEP1 and PKHD1 data achieve sufficient accuracy for predicting the recurrence of primary liver cancer. Since SVEP1 data impart a higher specifici-ty and PKHD1 data impart a higher sensitivity to the prognosis scores, the combined use of the two markers is better than being used individually.

Objective:To explore the clinicopathological characteristics and prognostic factors of neuroendocrine neoplasms(NENs)at different sites in the digestive system.Methods:The clinicopathological parameters and follow-up data were collected from 284 pa-tients with NENs in the digestive system in Tianjin Medical University Cancer Institute and Hospital from March 2011 to December 2015.The incidence and clinicopathological features were compared between the cases of NENs at different sites and survival analysis was performed.Results:In this study,NENs were detected mostly frequently in the pancreas,followed by the colorectum and stom-ach.In the pancreas,neuroendocrine tumor(NET)G1(51.8%)and G2(35.8%)accounted for a large proportion of NENs.World Health Organization(WHO)grades were related to lymph node metastasis,adjacent organ invasion,and nerve invasion(P<0.05 for all)but were not associated with the overall survival time of the patients.The patients with pancreatic NENs with distant metastasis had poor overall survival(P<0.05).Regarding colorectal NENs,most patients had NET G1(82.5%),and the majority of patients were cured with endoscopic or transanal resection.Patients with NENs,lymph node metastasis,and distant metastasis had poor overall survival(P<0.05 for all).The ratio of male-to-female patients,proportion of patients aged older than 40 years,prevalence of neuroendocrine carci-nomas(NECs)and mixed adenoneuroendocrine carcinomas(MANECs),presence of lymph node and distant metastasis,and presence of advanced stage tumors were greater in patients with gastric NENs than in patients with pancreatic and colorectal NENs(P<0.05 for all).WHO grades and lymph node metastasis were associated with the overall survival time of patients with gastric NENs(P<0.05 for both).Conclusions:NENs in the digestive system are a group of heterogeneous tumors with different clinicopathological features at different sites.The distribution and clinicopathological features of Chinese patients with NENs in the digestive system are different from those of European and American patients.More multicenter studies with large sample sizes are still needed to understand the bi-ological behaviors and prognostic factors of NENs at different sites in the digestive system.

Objective:To explore the diagnostic value of ultrasound-guided fine needle aspiration biopsy(US-FNAB)for thyroid nod-ules.Methods:The clinical characteristics and cytopathological diagnosis of patients with thyroid nodules in Tianjin Medical University General Hospital were analyzed retrospectively;the results of the cytopathological and pathological diagnoses were compared and an-alyzed.Results:Of the 1,241 US-FNAB samples,the ratio of men to women with thyroid nodules was 1:3.83(257/984).The incidence of thyroid nodules gradually increased from the age of 20 years and declined after the age of 60 years.The nodules,which were less than or equal to 1.0 cm in size,accounted for 51.57%(640 cases),and Thyroid Imaging Reporting And Data System(TIRADS)classifica-tion 4 accounted for 86.38%(1 072 cases).Of cyto-pathological diagnoses,22.00%(273 cases)were non-diagnostic,9.75%(121 cases) were benign,30.62%(380 cases)were atypia with undetermined significance,32.15%(399 cases)were suspicious for malignancy,and 5.48%(68 cases)were malignant.In the 302 patients who underwent surgery,the number of cases of clear diagnoses,unavailable di-agnoses,and atypia of undetermined significance were 203,21,and 78,respectively.In the 203 cases of clear diagnoses,the sensitivi-ty,specificity,positive predictive value,negative predictive value,precision,and misdiagnoses following US-FNAB of thyroid nodules were 100.00%(201/201),50.00%(1/2),99.50%(201/202),100.00%(1/1),99.51%(202/203),and 0.49%(1/203),respectively.In the 78 cases that were atypia of undetermined significance,the malignancy rate was 70.51%.Whether the atypia of undetermined signifi-cance was malignant or not was related to the TIRADS classification(P<0.05),and not related to the age,sex,tumor size,or location of the nodules(P>0.05).Conclusions:US-FNAB has high diagnostic value for thyroid nodules and is worthy of being popularized widely.If it replaced some intra-operative frozen sectioning procedures,it may reduce intra-operative waiting time and financial burden of pa-tients.

Long noncoding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides. Most lncRNAs have pro-nounced oncogenic effects associated with tumorigenesis and progression, promoting the proliferation, migration, invasion, and me-tastasis of tumor cells. The specific lncRNAs expression in particular types of cancers makes them promising diagnostic and prognostic biomarkers. Currently, studies on lncRNAs expression, functions, and mechanisms have attracted considerable attention in cancer re-search. However, these studies mainly focus on epitheliogenic malignant tumors. In this review, we outline the current state of infor-mation on lncRNAs and research progress on its role in haematopoietic and lymphoid tissue tumors.

Background and objective Progesterone and adiponectin receptor family member 3 (PAQR3) is a recently discovered tumor suppressor gene,which affects the development of a tumor by inhibiting cell proliferation,cell malignant transformation,angiogenesis,and tumor metastasis.This study investigates the expression of PAQR3 in lung cancer and its clinical significance.Methods A total of 106 patients with lung cancer received surgical treatment in hospital,and adjacent normal tissues of these patients were utilized as control group.The diagnosis of all patients was confirmed through clinical pathology.The expression of PAQR3 protein was detected by immunohistochemistry in lung cancer and adjacent normal tissues.The clinical significance of its expression was also investigated.Results The positive expression rate of PAQR3 protein in lung cancer was lower than that in adjacent normal tissues (P＜0.01).The positive expression rate of PAQR3 protein was unrelated to age,tumor size,and gender,but it exhibited a significant relationship with the pathological type and differentiation,TNM staging,and lymph node metastasis (P＜0.05).Kaplan-Meier survival analysis showed that the five-year survival rate of patients with PAQR3 protein positive expression was higher than that in patients with negative expression (P=0.026).Conclusion The expression of PAQR3 protein significantly decreased in lung cancer,indicating that PAQR3 protein plays an important role in the pathogenesis of PAQR3 in lung cancer.

Carcinoma, Non-Small-Cell Lung ; genetics ; therapy ; China ; Consensus ; Humans ; Lung Neoplasms ; genetics ; therapy ; Molecular Targeted Therapy

Objective:This study aims to determine the suitable cell line to be used in isolating cancer stem cells by comparing the characteristics of tumor stem cells in renal cell carcinoma cell lines SN12C and 786-O. Methods:The rate of sphere formation in SN12C and 786-O cells was determined in serum-free medium (SFM). The expression levels of CD133, CD44, Nanog, and Oct3/4 were investi-gated through flow cytometry. Moreover, the tumorigenicity of spheroid cell that originated from SN12C and 786-O cells was investi-gated in vivo by using a tumor model. Results:The average time of sphere formation in SFM was shorter in SN12C than in 786-O (5 days vs. 7 days). Moreover, the expression levels of CD133, CD44, Nanog, and Oct3/4 in SN12C and 786-O significantly differed (P<0.05). When transplanted in nude mice, 786-O spheres were less tumorigenic than SN12C spheres. Conclusion:SN12C spheres possess the main defining characteristics of renal cancer stem cell;thus, SN12C is the more suitable cell line to be used to isolate cancer stem cells compared with 786-O.

Objective To explore whether hypoxia could promote epithelial-mesenchymal transition (EMT) in various differentiated colorectal cancer cells, and analyse the effect of hypoxia on invasion and migration of colorectal cancer cells. Methods HCT116 (poorly differentiated) and HT-29 (highly differentiated) colorectal adenocarcinoma cells were selected respectively. The morphological changes of two cell lines were observed after 0,10,25,50,100 and 150 mg/L cobalt chloride (CoCl2) treatment for 48 h. The expression of hypoxia-inducible factor-1α(HIF-1α) protein was analysed after 0, 10,25,50,100 and 150 mg/L CoCl2 treatment for 48 h. An optimal concentration of CoCl2 was then selected. Methylthiazolyl tetrazolium (MTT) assay was used to detect the proliferation of two kinds of colorectal cancer cells induced by CoCl 2 at different time points (0, 24, 48, 72 and 96 h), and to select an optimal time. Under the optimal concentration and time conditions, the HCT116 and HT-29 cells were processed by hypoxia (hypoxia group) and normoxia (normoxic group). Transwell invasion assay and Wound healing assay were used to detect cell invasion and migration in two groups. Western blot assay and RT-PCR were used to detect protein and mRNA expression levels of HIF-1α, E-cadherin and Vimentin in two groups. Results Two kinds of cells showed obvious morphological changes after 50 mg/L CoCl2 treatment for 48 h. HIF-1αprotein level first increased and then decreased in two groups of cells with the increased concentration of CoCl 2, and 50 mg/L CoCl2 was the optimal concentration (P<0.05). The cell proliferation showed a tendency to decrease after the increase in both kinds of cells with or without hypoxia for 0-96 h (P<0.05), and 48 h was the optimal time. The transmembrane number and cell migration rate were significantly more in hypoxia group than those of normoxic group (P<0.05). The protein and mRNA levels of HIF-1α and Vimentin were significantly higher in hypoxia group than those of normoxic group in HCT116 and HT-29 cell lines (P<0.05). E-cadherin protein and mRNA levels were significantly lower in hypoxia group than those of normoxic group (P<0.05). Conclusion Hypoxia can promote EMT in different differentiated colorectal cancer cells, and can enhance invasion and migration of two kinds of colorectal cancer cells.