Poor Differentiation Group Research Articles

Assessment of the aggressiveness of rectal cancer using quantitative parameters derived from dual-energy computed tomography

PurposeTo evaluate the value of quantitative parameters derived from dual-energy computed tomography (DECT) in assessing the aggressiveness of rectal cancer. Materials and methodsSeventy-eight patients with rectal cancers confirmed by pathology underwent contrasted DECT scans. The normalized iodine concentration (NIC) and normalized water concentration (NWC) of the tumor against artery and tumor sizes were measured. The quantitative parameters were compared and statistically analyzed between subgroups based on the following prognostic factors: pretreatment carcinoembryonic antigen (CEA) levels, mesorectal fascia (MRF) status, T stage (T1,2 and T3,4), N stage (N0 and N1,2), tumor differentiation grade (poor differentiation, poor-moderate differentiation, moderate differentiation, moderate-well differentiation, well differentiation), and extramural venous invasion. ResultsThe differences of NIC values between MRF-free and MRF-invaded groups (P = 0.042), between T2 and T3–4 stage groups (P = 0.044), between N0 and N+ (N1, 2) groups (P = 0.036), between poor differentiation group and other differentiated groups (P < 0.05)were respectively significant. No significant differences of NIC values existed between CEA level or extramural venous invasion subgroups. For NWC values and tumor sizes, there were no significant differences between subgroups based on the prognostic factors above all. ConclusionsHigher NIC value is associated with a more aggressive tumor character. NIC value may have the potential to become an imaging biomarker of tumor aggressiveness.

Peripheral blood circulating microRNA-4636/-143 for the prognosis of cervical cancer.

Cervical cancer is the third leading cause of female death in the world. Serum microRNAs (miRNAs) are currently considered to be valuable as noninvasive cancer biomarkers, but their role in the prognosis of cervical cancer has not been elucidated. We aimed to find serum miRNAs that can be used as prognostic factors for cervical cancer. A traumatic pathological biopsy is the only reliable method for determining the severity of cervical cancer currently. Thus, noninvasive diagnostic markers are needed. The serological expression of candidate miRNAs were measured in 90 participants, including 60 patients withcervical cancer and 50 patients with cervical intraepithelial neoplasia. Two patients withcervical cancer were excluded from the study because of lack of data. miRNAs were evaluated by quantitative reverse transcription polymerase chain reaction. miR-143/-4636 appeared specific for cervical cancer compared with cervical intraepithelial neoplasia (P < .001). The classification performance of validated miRNAs for cervical cancer [Area under the receiver operating characteristic curve (AUC) = 0.942] was better than that reached by squamous cell carcinoma antigen (SCC-Ag; AUC = 0.727). Poor-differentiation group has lower miR-143/-4636 levels in serum (P < .05). miR-4636 level was correlated gross tumor volume and the depth of invasion (P < .0001). In our study, we found a combination of miR-143 and miR-4636 that is independently and strongly associated with cervical cancer prognosis and can be used as a clinically prognostic factor.

Metadherin overexpression in perihilar cholangiocarcinoma is associated with lymph node metastasis and poor prognosis.

Metadherin (MTDH) is a protein that is also named astrocyte elevated gene-1, and is highly expressed in a number of different tumor tissues. Although the expression of MTDH is associated with tumor invasion and recurrence, the expression of this protein in perihilar cholangiocarcinoma (PCCA) and its clinical use have not yet been investigated. In the present study, the expression of MTDH in patients with PCCA was investigated in order to determine its clinicopathological use. An immunohistochemical method was used to detect MTDH expression and the epithelial-mesenchymal transition markers E-cadherin and vimentin in 66 cases of PCCA. In addition to the expression of MTDH, the clinical and pathological data and the postoperative outcomes were analyzed. The MTDH positive expression rate was 48.5% (32/66) in PCCA. A significantly higher MTDH expression level was identified in the poor tumor differentiation group compared with the well differentiation group (P=0.007). In the positive lymph node metastasis group, a significantly higher MTDH expression level was revealed compared with the negative lymph node metastasis group (P=0.023). No association was noted with regard to the expression of MTDH and the variables age, sex, tumor diameter, tumor grade and tumor classification stage. Positive MTDH expression was significantly associated with high vimentin expression (P=0.037) compared with negative vimentin expression and inversely associated with positive E-cadherin expression compared with negative E-cadherin expression (P=0.030). Survival analysis suggested that the high MTDH expression group was associated with a worse overall survival (OS) rate and recurrence free survival (RFS) rate compared with the low MTDH expression group (P<0.001 and P=0.01, respectively). Cox regression analysis indicated that the Tumor-Node-Metastasis, surgery margin and high MTDH expression were independent OS and RFS factors for PCCA. MTDH expression may serve an important function in PCCA tumor growth and metastasis. Targeting MTDH may have important therapeutic applications for patients with PCCA.

Expression of programmed death-ligand 1, topoisomerase IIα and p16 proteins in cervical cancer and their significances

Objective To analyze the expression of programmed death ligand 1 (PD-L1), p16 proteins and DNA topoisomerase Ⅱα (TOPOⅡα) in cervical cancer and their clinical significances. Methods A total of 181 paraffin-embedded operating specimens and the biopsy including 106 cervical squamous cell carcinoma, 30 high grade cervical intraepithelial neoplasia (CIN), 30 low grade CIN and 33 normal cervical were selected from January 2014 to December 2015. An immunohistochemical EnVision method was used to detect the expression of PD-L1, p16 and TOPOⅡα. Results The positive rate of PD-L1 expression in cervical squamous cell carcinoma was 66.0% (70/106), but it was not expressed in high grade CIN, low grade CIN and normal cervical tissues, the differences were statistically significant (all P= 0.000). Whereas, in squamous cell carcinoma, the positive rate of PD-L1 in poor differentiation group [77.3% (51/66)] was higher than that in middle or high differentiation group [56.5% (21/40)], and the difference was statistically significant (χ2= 7.02,P= 0.01). According to the FIGO stage, the positive rate in stage Ⅰ-Ⅱ group [54.9% (28/51)] was lower than that in stage Ⅲ-Ⅳ group [76.4% (42/55)], and the difference was statistically significant (χ2= 5.47, P= 0.02). But there was no statistical significance in lesion size or lymph node metastasis (both P > 0.05). The positive rate of p16 in cervical squamous cell carcinoma was 99.1% (105/106), in high grade CIN was 86.7% (26/30), in low grade CIN was 26.7% (8/30), and no expression in normal cervical tissues, the differences were statistically significant (all P 0.05). The positive expression rate of TOPOⅡα in cervical squamous cell carcinoma was 97.2% (103/106), compared with that in high grade CIN [73.3% (22/30)], low grade CIN [66.7% (20/30)], and normal cervical tissues (no expression), the differences were statistically significant (all P= 0.000). But there was no significant difference in the positive expression rate of TOPO Ⅱα between high grade and low grade CIN (χ2= 0.32, P= 0.570). The expression of TOPOⅡα had no relationship with histological differentiation, FIGO stage, lesion size and lymph node metastasis (all P > 0.05). Conclusion The expression of PD-L1, p16 and TOPOⅡα is associated with the invasion of cervical cancer.PD-L1 may be an immune checkpoint for the treatment of patients with invasive cervical cancer. Key words: Uterine cervical neoplasms; DNA topoisomerases, type Ⅱ; Programmed death ligand 1; Genes, p16

Role of CT perfusion imaging in patients with variously differentiated gastric adenocarcinoma.

To explore the characteristics of variously differentiated gastric cancers on computed tomography (CT) perfusion imaging, including specific perfusion parameter values, and potential clinical applications in the prognosis assessment of gastric cancer. Fifty patients with gastric cancer confirmed by gastroscope pathology were studied prospectively using CT perfusion imaging examinations on a 64-slice spiral CT scanner. The acquired volume data were used for calculations, mapping, and analysis by using an abdominal tumor perfusion protocol (deconvolution method) in the CT perfusion software package to measure 4 parameters: blood flow (BF), blood volume (BV), mean transit time (MTT), and the permeability surface (PS) area product. The different differentiated Gastric cancers with CT perfusion values were divided into 3 groups: well-differentiated, moderately differentiated and poorly differentiated gastric adenocarcinoma, and compared statistically with one another by statistical software. The mean perfusion values of 10 patients with well-differentiated gastric adenocarcinoma were as follows: BF, 75.28 ± 6.81 mL/100 g/min; BV, 9.01 ± 0.94 mL/100 g; MTT, 9.89 ± 1.65 s; and PS, 10.05 ± 0.71 mL/100 g/min. The mean perfusion values of 24 patients with moderately differentiated gastric adenocarcinoma were as follows: BF, 110.01 ± 31.90 mL/100 g/min; BV, 18.18 ± 5.62 mL/100 g; MTT, 9.81 ± 3.69 s; and PS, 40.08 ± 15.82 mL/100 g/min. The mean perfusion values of 16 patients with poorly differentiated gastric adenocarcinoma were as follows: BF, 138.59 ± 38.09 mL/100 g/min; BV, 21.08 ± 4.11 mL/100 g; MTT, 9.47 ± 1.80 s; and PS, 57.50 ± 13.28 mL/100 g/min. Comparing the 3 groups, differences between the well-differentiated group and the moderate differentiation group were all statistically significant for BF, BV, and PS (p < 0.05, respectively), differences between the well-differentiated group and the poor differentiation group were all statistically significant for BF, BV, and PS (p < 0.05,respectively) as well; While MTT value showed no statistical difference among the 3 groups (p > 0.05). Stomach CT perfusion imaging is a functional imaging technology from the perspective of hemodynamics with potential clinical applications. The BF, BV and PS values could serve as indicators of the degree of malignancy and aid in prognostic assessment of gastric cancer.

Association Between Genetic Polymorphism of the MIF Gene and Colorectal Cancer in Taiwan.

Colorectal cancer (CRC) is the highest leading cause of cancer-related mortality in Taiwan. Macrophage migration inhibitory factor (MIF) has recently been defined as a novel protumorigenic factor that promotes cell proliferation, migration, and invasion. The aim of the present study is to identify the association between MIF gene polymorphism and CRC. A case-control study was designed to test the hypothesis. A total of 192 biopsy-diagnosed CRC patients (CRC) and 256 healthy subjects (control) were recruited. Genotyping of four single nucleotide polymorphism (SNPs; rs755662, rs11548059, rs1049829, rs1803976) at chromosome positions 755662 (5' UTR), 11548059 (exon2), 1049829 (exon2), 1803976 (exon3) was performed using a Taqman SNP genotyping assay. There is a significant difference in genotype frequency distribution of rs755662 polymorphism between CRC patients and controls (P = 0.011). No significant difference was found in the frequency distribution of rs11548059, rs1049829, rs1803976 polymorphism in CRC patients and controls (P = 0.660, P = 0.700, and P = 0.959, respectively). Moreover, the MIF-173 SNP was also significantly associated with young patients (age < 50 years, P = 0.026) late stage (Stage IV, P = 0.038) and poor differentiation group (P = 0.040). Compared to the control group, the MIF-173 SNP also significantly associated with patients with stages III and IV (P = 0.034 and 0.003, respectively). The presence of MIF-173 (G/C) gene polymorphism (rs755662) was associated with susceptibility, patient age, and stages of CRC in Taiwanese.

Aberrant promoter methylation of SFRP1 and SFRP2 gene in gastric cardia adenocarcinoma

Objective To investigate the promoter methylation status of SFRP1 and SFRP2 gene in gastric cardia adenocarcinoma (GCA). Methods Methylation specific PCR (MSP) method was used to examine the methylation status of the 5' CpG island of SFRP1 and SFRP2 gene in tumors and corresponding normal tissues. Results Methylation frequencies of SFRP1 and SFRP2 gene in tumor specimens were 87.2 % (82/94) and 83 %(78/94), which was significantly higher than that in corresponding normal tissues (14.9 % and 55.3 %, respectively) (P 0.05). 63 cases of GCA showed both of SFRP1 and SFRP2 gene simultaneous methylation, which including 36 cases of lymph node metastasis group, 27 cases of no lymph node metastasis group. Simultaneous methylation frequencies of SFRP1 and SFRP2 gene in lymph node metastasis group was higher than that in no lymph node metastasis group, poor differentiation group was higher than that in moderate and poor-moderate differentiation groups, but both of them did not show significant difference (P >0.05). Conclusion Promoter methylation of SFRP1 and SFRP2 might be related with oncogenesis of GCA and hypermethylation of SFRP1 gene might be related with the malignant behavior of GCA. Key words: Stomach neoplasms; Genes; Methylation; SFRP1; SFRP2

Detection of promoter hypermethylation of the CpG island of E-cadherin in gastric cardiac adenocarcinoma

AimAbnormal hypermethylation of CpG islands associated with tumor suppressor genes can lead to transcriptional silencing in neoplasia. The aim of this study was to investigate the promoter methylation and expression of E-cadherin gene in gastric cardiac adenocarcinoma (GCA).MethodsA nested MSP approach, immunohistochemistry method and RT-PCR were used respectively to examine the methylation status of the 5' CpG island of E-cadherin, its protein expression and mRNA expression in tumors and corresponding normal tissues.ResultsE-cadherin was methylated in 63 of 92 (68.5%) tumor specimens, which was significantly higher than that in corresponding normal tissues (P < 0.001). Methylation frequencies of stage III and IV tumor tissues was significantly higher than that in stage I and II tumor tissues (P = 0.01). Methylation status of poor differentiation group was significantly higher than moderate and poor-moderate differentiation groups (P < 0.01). By immunostaining 51 of 92 tumor tisssues demonstrated heterogeneous, positive immunostaining of tumor tissues (44.6%), significantly different from matched normal tissues (P < 0.001). Positive immunostaining of stage III and IV tumor tissues was significantly lower than stage I and II tumor tissues (P < 0.01). Poor differentiation group was also significantly lower than moderate and poor-moderate differentiation groups (P < 0.05). 80 percent of tumor tissues with E-cadherin gene methylated showed inactivated mRNA expression.ConclusionsHigh methylation status of the 5' CpG island of E-cadherin gene may be one of the mechanisms in the development of gastric cardiac adenocarcinoma.

Expression of glucose transporter in non-small cell lung carcinoma and its clinical significance

To investigate the expression of glucose transporter (Glut)1, Glut3, and hypoxia inducible factor (HIF)-1 alpha in human non-small cell lung carcinoma (NSCLC), and its clinical significance. Specimens of cancer tissues and paracancerous lung tissues from 34 cases of NSCLC and 17 specimens of benign lung lesions were collected. The expressions of Glut1, Glut3, and HIF-1 alpha were detected with immunohistochemical staining, RT-PCR, and Western blot. The relative mRNA expressions of Glut1 and HIF-1 alpha were 0.689 +/-0.245, 0.693 +/-0.248 in cancer tissues; and 0.338 +/-0.157, 0.351 +/-0.184 in paracancerous lung tissues (P <0.001); while those of Glut3 were 0.506 +/-0.246 in cancer tissues and 0.482 +/-0.238 in paracancerous tissues (P >0.05). The relative protein expressions of Glut1 and HIF-1 alpha were 0.582 +/-0.247, 0.525 +/-0.246 in cancer tissues and 0.288 +/-0.151, 0.261 +/-0.135 in paracancerous lung tissues (P<0.001), but the protein expressions of Glut3 were 0.551 +/-0.251 and 0.436 +/-0.224 respectively (P>0.05). Glut1 and HIF-1 alpha expressions were higher in poor differentiation group and in stage III group, than those in medium and well differentiation group and stage I and II group. Moreover, there was a significant correlation between the expression of Glut1 and HIF-1 alpha (r=0.854, P<0.01). Glut1 and HIF-1 alpha are highly expressed in NSCLC, and their expressions are associated with tumor differentiation and clinical stage.

Expression of CD44s mRNA in gastric carcinoma

To study the expression of CD44s mRNA in the occurrence, development and invasion of gastric carcinoma (GC). The expressions of CD44s mRNA in 66 cases of GC, 25 cases of superficial gastritis and 25 cases of atypical hyperplasia were examined by in situ hybridization (ISH). There was no expression of CD44s mRNA in the group of superficial gastritis; the positive rate was 20%(5/25) in the group of atypical hyperplasia and 62.12%(41/66) in the group of gastric carcinoma. The positive rate in poor differentiation group was significantly higher than that in well differentiation group (P<0.05), and the positive rate of lymph node metastasis group was significantly higher than that in negative lymph node metastasis group(P<0.05). The expression of CD44s mRNA was related to cell differentiation degree and lymph node metastasis, the activation of CD44s gene was related to strong invasion of cancer cells and poor prognosis.

Expression of RASSF1A mRNA and its relationship with HPV-16 in cervical cancer

To study the expression of RASSF1A mRNA and its relationship with HPV-16 in cervical cancer. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of RASSF1A mRNA in 56 patients with cervical cancer, 36 patients with CIN and 20 patients with normal cervix. HPV-16 DNA was also examined by PCR in 56 patients with cervical cancer. The rates of loss of RASSF1A mRNA expression were 0% (0/20), 22.2% (8/36) and 50.0% (28/56) in patients with normal cervix, CIN and cervical cancer respectively. The loss rate of RASSF1A mRNA in the cervical tissues at the advanced stages (stages III-IV, 82.4%) was higher than that at the early stages (stages I-II, 35.9%, P < 0.05). RASSF1A mRNA deletion occurred more often in the tissues of squamous cervical cancers (63.3%) than in those of adenocarcinoma (34.6%) (P < 0.05). The loss rate of the poor differentiation group was 70.8%, significantly higher than that of the middle and high differentiation group (37.5%, P < 0.05). The loss of RASSF1A was negatively related with HPV-16 infection in cervical cancers, especially in adenocarcinoma (P < 0.905). Loss of RASSF1A may play an important role in tumorgenesis and development of cervical cancer.

The preliminary study on the quantitative color image analysis on immunohistochemical staining of squamous cell lung carcinoma

To study the differences and usage of the color indexes in the quantitative image analysis on immunohistochemical staining of squamous cell lung carcinoma between moderate differentiation and poor differentiation. S-P method was used in p53, PCNA and p16 immunohistochemical staining of squamous cell lung carcinoma. Quantitative image analysis was performed with Computer Assisted Pathological Image Analysis System. There was no well differentiation case of the 20 cases. Positive stain of p53 was observed in 6 cases in moderate differentiation group and 6 cases in poor differentiation group respectively. Positive PCNA stain existed in 7 cases in moderate differentiation group and 6 cases in poor differentiation group respectively. Five cases in moderate differentiation group and 6 cases in poor differentiation group had p16 expression deletion. The saturation of p53 staining was lower in moderate differentiation group (4.95%) than that in poor differentiation group (10.95%) (t=4.208,P=0.002). The saturation of PCNA staining was lower in moderate differentiation group (7.74%) than that in poor differentiation group (12.98%) (t=2.416,P=0.034). The hue of p16 staining was lower in moderate differentiation group (53.98⁰) than that in poor differentiation group (62.32⁰) (t=2.784,P=0.021). The color indexes in the quantitative immunohistochemical image analysis may reflect the differentiation degree of squamous cell lung carcinoma.