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Soft tissue sarcomas (STSs) are a rare and fascinating group of diseases that can be subdivided into specific reciprocal translocations in STSs (SRTSs) and nonspecific reciprocal translocations in STSs (NRTSs). PTEN mutations are rare in STSs, suggesting that PTEN expression may be lost by alternative mechanisms such as methylation. In order to reveal whether aberrant PTEN methylation occurs in STSs, MassARRAY Spectrometry was carried to detect methylation patterns of PTEN in STSs. We evaluated methylation levels in 41 CpG sites from −2,515 to −2,186 bp (amplicon A) and −1,786 to −1,416 bp (amplicon B) relative to the translation initiation site in 110 different cases (46 cases of SRTSs, 40 cases of NRTSs, and 24 cases of normal controls). In addition, immunohistochemistry (IHC) was used to detect the loss of PTEN to determine whether PTEN alterations were responsible for decreased PTEN expression. Our data showed that expression of PTEN was diminished in 49 (57%) STSs, whereas the remaining cases (43%) were classified as high expression. Our previous results found that only 2 of 86 cases (2.3%) had a PTEN mutation suggesting that PTEN may be mainly downregulated in STSs by methylation, but not by mutation of PTEN itself. We observed that amplicon A was hypermethylated in STSs with low PTEN expression, whereas normal controls had low methylation levels (P<0.0001), which was not present in amplicon B (P>0.05), nor were there significant differences in the methylation levels in PTEN between SRTS and NRTS cases. The majority of individual CpG units within two amplicons was demonstrated to be hypermethylated. These findings indicate that PTEN hypermethylation is a common event in STSs suggesting that the inactivation of PTEN may be due to hypermethylation in the promoter of PTEN. The aberrant methylation of the CpG sites within PTEN promoter may serve as a potential candidate biomarker for STSs. [ABSTRACT FROM AUTHOR]

This study aimed to investigate vitamin D receptor (VDR) expression levels and evaluate their clinical significance in patients with colorectal cancer (CRC). VDR protein expression was validated by immunohistochemistry in 188 CRC tissues and 134 normal colorectal tissues. The associations between VDR expression and clinicopathologic characteristics, including prognostic outcomes, were analyzed. VDR expression in normal colorectal tissue was higher than that in CRC (83.6% versus 34.6%, P = 4.489 × 10 -20 ) and generated moderate diagnostic performance for CRC detection (AUC = 0.88, sensitivity = 0.87, specificity = 0.84). Low VDR expression was associated with invasion depth (P = 0.001) and poor survival in CRC (P = 0.031). Univariate Cox analysis demonstrated VDR expression (P = 0.036) was a significant prognostic predictor for survival in patients with CRC. Low VDR expression could be a valuable diagnostic and prognostic biomarker for CRC patients. Targeting VDR may offer a potential therapeutic strategy for blocking CRC., Competing Interests: None., (IJCEP Copyright © 2020.)

Multiple chromosome aberrations are responsible for tumorigenesis of esophagus squamous cell carcinoma (ESCC). To characterize genetic alterations by comparative genomic hybridization (CGH) and their relation to ESCC, We enrolled 54 members with ESCC from Kazakh's patients. We found that the deletions of 3p (P = 0.032), 17p (P = 0.004), 22q (P = 0.000) and gains of 5p (P = 0.000), 11q (P = 0.000) were significantly correlated with the location of tumors. Losses of 1p (P = 0.005), 3p (P = 0.006), 22q (P = 0.024) and gains of 3q (P = 0.043), 8q (P = 0.038), 18q (P = 0.046) were also found more frequently in patients with larger diameter disease. The loss of 19q (P = 0.005) and gains of l3q (P = 0.045), 18p (P = 0.018) were significantly correlated with pathologic grade. The gain of 7p (P = 0.009) and deletion of 19q (P = 0.018) were seen more frequently in patients with Grade III-IV tumors. Chromosome amplifications in ESCC at 1q (P = 0.008), 7p (P = 0.008), 8q (P = 0.018) and deletions at 3p (P = 0.021), 11q (P = 0.002), 17p (P = 0.012) were related to lymph node metastasis; the gains of 1q (P = 0.026) and 6q (P = 0.017) and the loss of 11q (P = 0.001) were significant in different isoforms of HPV infection. We identified some chromosomes in which the genes were related to the tumorgenesis of ESCC, which may be a theme for future investigation., Competing Interests: None., (IJCEP Copyright © 2018.)

Tumor-associated macrophages (TAMs), the most important immune cells in tumor microenvironment, were reported to play a key role in cancer progression, but the correlation of TAMs and Kazakh esophageal squamous cell carcinoma (ESCC) was still not clear, so we sought to identify the function of TAMs in Kazakh ESCC clinicopathological and prognostic evaluation. CD68 as the TAMs marker, and immunohistochemistry (IHC) was used to quantify the TAMs infiltrated in tumor nest and stroma, the IHC staining was also used to evaluate the expression of MMP-9 in Kazakh ESCCs. The density of CD68-TAMs in ESCCs tumor nest and stromal, were significantly higher than those of CANs (P<0.05). The increasing number of CD68-positive TAMs in tumor nest and stromal were positively associated with tumors lymph node metastasis and clinical stage (P<0.05). The expression of MMP-9 in Kazakh ESCCs was higher than that of CAN tissues (P<0.05). Increased MMP-9 expression in ESCCs was significantly associated with lymph node metastasis and tumor clinical stage (P<0.05). Importantly, the number of CD68-positive TAMs in ESCCs was significantly correlated with the expression of MMP-9 (P<0.05). Furthermore, the survival analyses demonstrated that high-density of CD68-TAMs in tumor nest was positively related to the shorter overall survival time of patients (P<0.05). Increasing numbers of CD68-TAMs promote higher expression of MMP-9 and may play an important role in the occurrence and progression of Kazakh ESCCs, and which could be used as important prognostic markers for Kazakh ESCCs., Competing Interests: None., (IJCEP Copyright © 2017.)

Esophageal squamous cell carcinoma (ESCC) is one of the frequent malignant tumors with poor prognosis worldwide. Identifying the prognostic biomarkers and potential mechanisms of such tumors has attracted increasing interest in esophageal cancer biology. Our previous study showed that phospholipase C elipson 1 (PLCE1) expression is up-regulated and associated with disease progression in esophageal carcinoma. MicroRNAs (miRNAs) play vital roles in regulating its target gene expression. However, studies on miRNA-regulated PLCE1 expression and its cellular function are still very few. We found that miR-34a is significantly expressed lower in ESCC tissues. We further showed that PLCE1 is a direct functional target gene of miR-34a, and the functional roles of miR-34a in ESCC cell lines in vitro were also determined through gain- and loss-of-function analyses. Results revealed that miR-34a functions as a tumor suppressor by inhibiting the proliferation, migration, and EMT phenotype, as well as promoting apoptosis of ESCC cell lines. Moreover, PLCE1 is overexpressed in ESCC tumors and promotes tumorigenicity in vivo and vitro. PLCE1 expression is negatively correlated with miR-34a profiles in ESCC tissues. Our data suggest that miR-34a exerts its anti-cancer function by suppressing PLCE1. The newly identified miR-34a/PLCE1 axis partially illustrates the molecular mechanism of ESCC metastasis and represents a new candidate therapeutic target for ESCC treatment., Competing Interests: CONFLICTS OF INTEREST The authors claim that they have no competing interests to disclose about this article.

Phospholipase C epsilon 1 (PLCE1) is a susceptibility gene in esophageal squamous cell carcinoma (ESCC). Nevertheless, the role of PLCE1 in ESCC tumorigenesis has not been elucidated. In this study, we determined the function of PLCE1 and its regulatory microRNA (miRNA) in ESCC. PLCE1 protein was excessively expressed in ESCC and precancerous lesions compared with that in normal tissues. High PLCE1 expression levels in ESCC were significantly linked with poor overall survival. Knockdown of PLCE1 promoted the apoptosis, cytokine-induced apoptosis, and sensitivity of cancer cells to chemotherapeutic drugs but abrogated the proliferation and EMT phenotype of ESCC in vitro. Notably, miR-145 was newly identified as a potent repressor of PLCE1 expression by directly targeting the 3'UTR of PLCE1. MiR-145 also inhibited cell proliferation, migration, and metastasis, as well as controlled the cytoskeleton dynamics of esophageal cancer. Moreover, miR-145 was expressed at low levels in a large cohort of patients with ESCC and was inversely correlated with PLCE1 protein expression in cancer cells and tissues. These findings demonstrate that PLCE1 functions as tumor promoter in ESCC and can be suppressed by miR-145 through inhibition of PLCE1 translation. Hence, delivery of PLCE1-targeting miR-145 is a potential therapeutic approach for esophageal cancer.

Background: Many studies have suggested a relationship between human papillomavirus (HPV) infection and the risk of esophageal squamous cell carcinoma (ESCC). However, findings are inconclusive, potentially because of geographic heterogeneity and variations in detection methods., Objectives: We sought to further investigate the prevalence of HPV with a new detection method, the MassARRAY Sequenom technique, in esophageal squamous cell carcinomas occurring in patients belonging to Kazakh populations in Xinjiang, China., Study Design: In the present study, a novel genotyping method for detecting 30 HPV genotypes, specifically by genotyping both the HPV E6 and L1 genes with multiplex PCR using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) (PCR-MS) was first adopted to evaluate HPV genotypes in 89 esophageal cancer samples and 49 matched adjacent normal esophageal tissues., Results: Six HPV genotypes (HPV6, HPV16, HPV33, HPV39, HPV51, and HPV82) were present in at least 51.7% of the esophageal carcinoma tissues, which was significantly greater than 28.6% prevalence among controls (P < 0.05). HPV16 was the most common of all the genotypes investigated (HPV16 prevalence in carcinoma tissue: 49.4%; odds ratio 3.02, 95% confidence interval 1.39-6.53). HPV-positive ESCC patients were generally younger than HPV-negative patients (P = 0.04). In addition, HPV infection was more common in cases of well-differentiated and shallower invasive depth., Conclusions: Based on this new detection method, our findings reiterate the possibility that HPV infection (especially HPV16) may be involved in the etiology of esophageal carcinoma in the Kazakh populations and that HPV E6 gene positivity may be associated with prognosis of patients.

Background: Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with a strong tendency toward familial aggregation and a higher incidence as well as mortality in Kazakh population. Tumor necrosis factor-alpha (TNF-α) is an important inflammatory cytokine that plays a role in controlling the progression of lung cancer, hepatocellular cancer, breast cancer and gastric cancer. But the association between TNF-α-308G/A and ESCC still remains unclarified., Materials and Methods: Here, we investigated the potential associations between the TNF-α-308G/A and susceptibility to ESCC in 212 cases and 200 controls from a pure ethnic population of Kazakh. DNA extraction and Real-time PCR were performed to detect the TNF-α-308G/A expression levels and odd ratios (ORs) with the corresponding 95% confidence interval (CI) were to evaluate their association with TNF-α-308G/A polymorphism., Results: We found that the frequencies of TNF-α-308G/A in the cases were similar to that of the controls with no differences being statistically significant (χ(2)=1.23, P>0.05). Using the G allele as the reference genotype, individuals who carried A allele had a significantly increased risk of developing ESCC (OR=2.64, 95% CI=1.31~5.35). Especially, the G/A+A/A genotype are associated with increased risk of metastatic as compared with GG genotype individuals (OR=2.08, 95% CI=1.14-3.80, P=0.02)., Conclusions: Our findings suggest that though the TNF-α-308G/A polymorphism may not be correlated with the susceptibility to Kazakh's ESCC in Xinjiang, patients who carry A allele tend to poorly differentiated and lymph node metastasis.

Human papillomavirus (HPV) infection is a major risk factor for cervical cancer. However, only some high risk human papillomavirus (HR-HPV)-infected women progress to cervical cancer, host immunogenetic factors human leukocyte antigen (HLA) may account for viral antigens presenting individually or together in the progression to cervical cancer. This study examined the association between the development of invasive cervical cancer (ICC) and the determinant factors including HLA-DRB1*1501 and DQB1*0602, HR-HPV infection among Chinese Uighur and Han populations. Blood samples, cervical swabs and biopsies were obtained from 287 patients with ICC (192 Uighurs and 95 Hans) and 312 healthy controls (218 Uighurs and 94 Hans). HPV DNA was detected by PCR and HLA-DRB1*1501 and DQB1*0602 alleles were performed using PCR-SSP method. HPV16 infection rates was significantly higher among Uighur and Han with ICC as compared to healthy controls (OR = 58.317; 95% CI: 39.663-85.744; OR = 33.778; 95% CI: 12.581-90.691; P < 0.05 for all). HLA-DRB1*1501 (OR = 0.305; 95% CI: 0.115-0.813; P < 0.05) and HLA-DRB1*1501-DQB1*0602 haplotype frequencies (OR = 0.274; 95% CI: 0.086-0.874; P < 0.05) were significantly reduced in Han ICC. The HLA-DQB1*0602 frequency significantly decreased among Uighur women with ICC (OR = 0.482; 95% CI: 0.325-0.716; P < 0.05). Similar tendencies were observed for DQB1*0602 with HPV16-positive ICC (OR = 0.550; 95% CI: 0.362-0.837; P < 0.05). This study suggests that HLA-DRB1*1501 and DQB1*0602 alleles may influence the immune response to HPV16 infection and decrease the risk of ICC among Uighurs and Hans in Xinjiang, China.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) derived from plasmacytoid dendritic cell precursors is a very rare, and characterized by cutaneous and bone marrow involvement and leukemic spread. The neoplasm presents with an aggressive behavior, and the clinical findings include cytopenia, particularly thrombocytopenia. The tumor cells are negative for antigens of T- and B- cell lines. However, these cells express CD4, CD56 and CD123, which are markers of plasmacytoid dendritic cells, and negative for Epstein-Barr virus (EBV). From this point of view, a 71-year-old man who was initially found to have a cutaneous mass on his face and thorax was reported here, and initially was diagnosed as "eczema". The skin rashes then became aggravated on a trial of low dose topical corticosteroid for 2 months. According to skin biopsy, the tumor cells reveal an immature blastic appearance and positive for CD4 and CD56, negative for CD3, CD20, indicating a diagnosis of BPDCN. Here, we report the dismal course of a patient with BPDCN without accepting further therapy, and only survived 3 months.

Objective: To investigate the association between the rs2274223 and rs3765524 polymorphism of phospholipase C epsilon 1 (PLCE1) gene and the susceptibility to develop esophageal squamous cell carcinoma (ESCC) in a pure Kazakh Chinese population., Methods: Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) was utilized to genotype the potentially functional single nucleotide polymorphism rs2274223 A>G and rs3765524 C>T of PLCE1 in an ongoing hospital-based and case-control study of 200 ESCC cases with 300 cancer-free age ( ± 5 years) and sex matched controls. Statistical analyses were performed with Statistical Products and Services Solutions software (version 13.0). Adjusted odds ratios (OR) and 95% confidence evaluation intervals (95%CI) measured by multivariate logistic regression analysis were adopted to study the correlation of the gene polymorphism with the susceptibility to ESCC., Results: The genotype frequencies observed for rs2274223 was consistent with Hardy-Weinberg equilibrium in controls. Univariate analysis revealed significant differences between cases and controls with respect to genotype distribution for rs2274223 (P = 0.006). The variants of rs2274223 were found to confer significantly increased risk of ESCC (GG vs AA: OR = 3.17, 95%CI = 1.45-6.93; AG/GG vs AA: OR = 1.55, 95%CI = 1.08-2.22) in the Kazakh Chinese population. Moreover, AG/GG genotype of rs2274223 was found to be significantly associated with poorly-differentiated ESCC (OR = 2.48, 95%CI = 1.10-5.60). When the ESCC patients were divided into two subgroups, stage I/II and stage III/IV according to the AJCC TNM classification, the GT/GG genotype of rs2274223 was significantly associated with stage III/IV ESCC (OR = 1.85, 95%CI = 1.05-3.25). No significant association was found between rs3765524 and Kazakh ESCC., Conclusions: These results indicate that rs2274223 site polymorphism of the PLCE1 gene is strongly associated with risk of ESCC in a Kazakh Chinese population, especially the poorly-differentiated and stage III/IV ESCC.

p53 and PTEN are the two most frequently mutated tumor suppressors in human cancer. However, literature on the effect of the joint inactivation of tumor-suppressor genes in soft tissue sarcoma (STS) is lacking. The purpose of this study was to investigate whether p53 and PTEN mutations play a role in the carcinogenesis of STS, as well as to evaluate their mutual role in STS pathogenesis. We screened mutations of p53 and PTEN in 86 human STSs using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing, respectively. p53 mutations were detected in 25.6% (22 out of 86) of STSs: 6 cases of p53 mutations were detected in 46 cases of specific reciprocal translocations in STSs (13.0%), 16 cases were detected in 40 cases of nonspecific reciprocal translocations in STSs (40.0%); the majority of the mutations were point mutations in exon 6-7. Furthermore, PTEN mutations were observed in 2 out of 86 STSs (2.3%). Two out of 86 cases revealed a 130th codon G>A missense mutation in exon 8 of PTEN which resulted in an Arg change to Gln in the PTEN protein structure; and a 334th codon A>T missense mutation in exon 8 of PTEN, which resulted in an Asn change to Lys in the PTEN protein structure. All subjects were examined for p53 exon 5-9 mutations and for PTEN exon 5-9 mutations. However, no tumors contained an alteration of the two genes. The findings indicate that p53 mutations may be involved in the oncogenesis of STS and also suggest that p53 may function as a potential molecular marker for distinguishing between STSs with specific reciprocal translocations and nonspecific reciprocal translocations. Although the existence of PTEN mutations in STS was detected, the PTEN mutation frequency was quite low. We conclude that PTEN may have played a less prognostic role than p53 in the development and malignant transformation of STS in the patients examined.

Objective: To investigate the polymorphism of HLA-DRB1 and DQB1 allele in esophageal squamous cell carcinomas of Kazakh in Xinjiang, and to characterize susceptible genes for the family of Kazakh esophageal squamous cell carcinoma., Methods: HLA-DRB1*0901, DRB1*1501, DQB1*0301, DQB1*0602 alleles were genotyped by sequence specific primers using polymerase chain reaction (PCR-SSP) in 200 Kazakh esophageal squamous cell carcinoma and 177 normal esophageal mucosa., Results: The frequency of HLA-DRB1*1501, HLA-DQB1*0301, HLA-DQB1*0602 alleles in 200 Kazakh esophageal squamous cell carcinoma (0.455, 0.760 and 0.690) were significantly higher than that of 177 normal esophageal mucosa (0.232, 0.520, 0.554; OR = 2.78, 2.93, 1.80; P < 0.05). The frequency of HLA-DRB1*0901 between the carcinoma (0.105) and control groups (0.102) had no association (OR = 1.036, P > 0.05); The frequency of HLA-DQB1*0602 was higher in poor-differentiated squamous cell carcinomas (0.742) than that of well-differentiated tumors (0.597, P < 0.05)., Conclusions: HLA-DRB1*1501, HLA-DQB1*0301, HLA-DQB1* 0602 may be susceptible to Kazakh esophageal squamous cell carcinoma. HLA-DQB1*0602 correlates with well-differentiated esophageal squamous cell carcinoma.

Background: Previous cytogenetic studies revealed aberrations varied among the three subtypes of rhabdomyosarcoma. We profiled chromosomal imbalances in the different subtypes and investigated the relationships between clinical parameters and genomic aberrations., Methods: Comparative genomic hybridization was used to investigate genomic imbalances in 25 cases of primary rhabdomyosarcomas and two rhabdomyosarcoma cell lines. Specimens were reviewed to determine histological type, pathological grading and clinical staging., Results: Changes involving one or more regions of the genome were seen in all rhabdomyosarcomal patients. For rhabdomyosarcoma, DNA sequence gains were most frequently (> 30%) seen in chromosomes 2p, 12q, 6p, 9q, 10q, 1p, 2q, 6q, 8q, 15q and 18q; losses from 3p, 11p and 6p. In aggressive alveolar rhabdomyosarcoma, frequent gains were seen on chromosomes 12q, 2p, 6p, 2q, 4q, 10q and 15q; losses from 3p, 6p, 1q and 5q. For embryonic rhabdomyosarcoma, frequent gains were on 7p, 9q, 2p, 18q, 1p and 8q; losses only from 11p. Frequently gained chromosome arms of translocation associated with rhabdomyosarcoma were 12q, 2, 6, 10q, 4q and 15q; losses from 3p, 6p and 5q. The frequently gained chromosome arms of nontranslocation associated with rhabdomyosarcoma were 2p, 9q and 18q, while 11p and 14q were the frequently lost chromosome arms. Gains on chromosome 12q were significantly correlated with translocation type. Gains on chromosome 9q were significantly correlated with clinical staging., Conclusions: Gains on chromosomes 2p, 12q, 6p, 9q, 10q, 1p, 2q, 6q, 8q, 15q and 18q and losses on chromosomes 3p, 11p and 6p may be related to rhabdomyosarcomal carcinogenesis. Furthermore, gains on chromosome 12q may be correlated with translocation and gains on chromosome 9q with the early stages of rhabdomyosarcoma.

Objective: To study the clinical and morphological features, immunophenotype and in situ detection of Epstein-Barr virus (EBV) infection in infectious mononucleosis (IM) to enhance the knowledge and diagnosis of the disease., Method: Using routine haematoxylin and eosin staining, immunohistochemistry and EBER in situ hyhridization together with clinical data analysis, 15 cases of IM were evaluated for their clinical features, morphology, immunophenotype and EBV infection status., Results: IM was common in children and young adults with a median age of 18 years. It was an acute disease with lymphadenopathy and frequently fever. Most of the patients had a rapid recovery. Every case showed a markedly T zone expansion with a mottling pattern, composing of small to large lymphocytes, plasma cells and histiocytes. The cells also showed a B-cell differentiation profile ranging from activated lymphoblastoid cells, immunoblasts, plasmablasts, plasma-like cells and plasma cells. Many small lymphocytes in the expanded T zone expressed CD3. Some of the activated lymphoblastoid cells and immonoblasts were CD20 and CD30 positive with variable intensity signals. EBER positive (nuclear staining) cells were seen in every case. The number of EBER positive cells ranged from 10 to more than 100 per high power field. These cells included small to large lymphocytes locating mostly in the expanded T zone and a few were in the follicular germinal centers., Conclusions: IM is an EBV related acute sell-recovering lymphoproliferative disease, having distinct clinical, morphological and immunophenotypic characteristics as well as EBV infection. Taking these features into consideration will facilitate the correct diagnosis of IM.