Role of CTLA4 immunohistochemistry in the diagnosis of colon cancers

Background: There are a wide range of diagnostic markers for colorectal cancers like detection of mutated KRAS, TP53, and APC genes. However, genetic and immunological factors have also been attributed to the cancer prognosis. The present study was carried out to evaluate the expression of CTLA-4 in colorectal cancers. Methods: This cross-sectional study was carried out among 30 resected specimens of colorectal cancer. Paraffin blocks were made on samples from tumor areas along with adjacent normal areas. Immunohistochemistry for CTLA-4 was done on the sections along with controls. Gross findings were recorded from the blocks. Blocks with section containing normal epithelium and tumor were chosen for immunohistochemistry. Results: Overexpression of CTLA-4 was observed in 43.3% of the tumors. There was a significantly high tumor infiltration among those specimens showing overexpression of CTLA-4. The observed difference was statistically significant (P < 0.05). On comparing the grade of the tumor with intensity of CTLA4 uptake, it was observed that majority of the well-differentiated tumors (66.7%) had an intensity of 1+ whereas majority of the poorly differentiated tumors had an intensity of 3+ (66.7%). Conclusion: The present study has demonstrated overexpression of CTLA-4 in colorectal cancer specimens, and also highlighted the potential scope for anti-CTLA-4 agents like Ipilimumab in cancer therapy. The need for further evaluation to examine five-year survival with such immunotherapies is essential to document candid therapeutic recommendations for colorectal cancers.

Analysis on clinicopathological features of 617 patients with colorectal cancer / 中国内镜杂志

Objective To summarize the clinicopathological features with 617 cases colorectal cancer and explore reliable clues for early diagnosis. Methods Retrospective analysis of clinical, endoscopic, pathological features and DNA mismatch repair of 617 cases of colorectal cancer was made from January 2008 to March 2017. Results The overall diagnostic yield of colorectal cancer was 2.35% (596/25 308). 18 patients were diagnosed as simultaneous multiple colorectal cancer (3.02%, 18/596). Males and females ratio is 1.34 : 1.00. The average age diagnosed was 66.8 years old. The proportion of colon cancer was 76.68% (457/596), while cancer located in right side of the colon was 39.17%. Occurrence rate of right colonic cancer were higher in female group (47.34%) than that in male group (33.46%) (P = 0.003). Well and moderately differentiated adenocarcinoma was observed in 84.60% (522/617) of the patients. The ratio of mucinous adenocarcinoma was 6.81% (42/617). Totally 230 patients received the DNA mismatch repair, and 57 patients were diagnosed as defective DNA mismatch repair (24.78%). Defective DNA mismatch repair (dMMR) was associated with right colonic cancer, poorly differentiated adenocarcinoma, signet-ring carcinoma and mucinous adenocarcinoma (P < 0.05). Conclusions Colonoscopy screening in the elderly patients deserves great attention. Raise awareness of simultaneous multiple colorectal cancer. Pay attention to the screening of right colon cancer in female. The DNA mismatch repair should be detected in right colonic cancer, poorly differentiated adenocarcinoma, signet-ring carcinoma and mucinous adenocarcinoma.

The mechanism of 5-Fu-based drug resistance in DNA mismatch repair deficient colorectal cancer HCT-116 cells / 药学实践杂志

Objective To study the mechanisms of the drug resistance of DNA mismatch repair (MMR) deficient color-ectal cancer (CRC) HCT-116 to 5-fluorouracil (5-Fu) .Methods MLH1 deficiency HCT-116 cells were transfected with pcD-NA3 .1-MLH1 Vector .The expression of MLH1 was detected by Western blot .The change of resistance against 5-Fu was ex-amined by detecting the cell viability with CCK-8 kits .The expression of CD133 (cancer stem cell marker ) and CK8 & CK20 (cell differentiation marker) were detected by flow cytometry .Results Comparing to HCT-116 control group ,the viability of HCT-116 cells was markedly decreased (P<0 .01) after stable expressing MLH1 ,accompanied by the down-regulated expres-sion of CD133 on the cell surface .Moreover ,the up-regulation of cell differentiation marker CK8 and CK20 was observed in HCT-116 cells with stable expressing MLH1 .Conclusion Our data indicated that the expression of MLH1 was associated with down-regulated CD133+ stem-like cells in colorectal cancer HCT-116 with MLH1 deficiency .Therefore ,CD133+ stem-like cells may related to the drug resistance of MMR deficiency tumor .This study provides a possible theory to explain the 5-FU resist-ance in the colorectal cancer patients with MMR deficiency .

Clinical and Biological Features of Interval Colorectal Cancer

Interval colorectal cancer (I-CRC) is defined as a CRC diagnosed within 60 months after a negative colonoscopy, taking into account that 5 years is the “mean sojourn time.” It is important to prevent the development of interval cancer. The development of interval colon cancer is associated with female sex, old age, family history of CRC, comorbidities, diverticulosis, and the skill of the endoscopist. During carcinogenesis, sessile serrated adenomas/polyps (SSA/Ps) share many genomic and colonic site characteristics with I-CRCs. The clinical and biological features of I-CRC should be elucidated to prevent the development of interval colon cancer.

Investigation of key miRNAs and their target genes in inflammatory bowel diseases and colitis-associated colorectal cancers using miRNA proifling and bioinformatic tools / 中国癌症杂志

Background and purpose:Inlfammatory bowel diseases (IBD) are a group of chronic intestinal diseases, including ulcerative colitis (UC) and Crohn’s disease (CD). This study identified differentially expressed miRNAs in UC, CD and colitis-associated colorectal cancers (CAC) to explore their potential as novel molecular biomarkers. Methods:Tissue samples were taken from 13 UC patients, 3 CD patients, 12 CAC patients, and 8 age-and gender-matched healthy controls. The miRNA expressions were detected by real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) assay. Known targets of deregulated miRNAs were utilized using miRWalk 2.0 database, and subsequent bioinformatics analysis of these target genes was performed by DAVID software (GO-analysis, KEGG-analysis and BIOCARTA-analysis). Results:The data showed that miR-146a, miR-27a, miR-29a, miR-20a and miR-21 were upregulated in UC, CD and CAC tissues compared with normal control. Moreover, the target genes of these miRNAs were enriched in several key signal transduction pathways including cancer-related pathway and immu-nity-associated pathway. Conclusion:miR-146a, miR-27a, miR-29a, miR-20a and miR-21 may play important roles in the switching from IBD to CAC.

The Stromal Overexpression of Decay Accelerating Factor (DAF/CD55) Correlates with Poor Clinical Outcome in Colorectal Cancer Patients

BACKGROUND: Decay accelerating factor (DAF/CD55), regulates the complement system by accelerating decay of the C3 convertase, has been described in several malignancies, however, the clinicopathologic significance of CD55 and its receptor CD97 has not been fully investigated. We examined the expression patterns of both CD55 and CD97 and their association with clinicopathologic parameters in colorectal cancers (CRCs). METHODS: Expression patterns of CD55 and CD97 in the stroma and tumor cells at tumor center and invasive front were examined in 130 CRCs, and their significance was statistically evaluated. RESULTS: CD55-high stroma was correlated with tumor border (p=0.006) and invasion depth (p=0.013). CD55-high tumor cells at tumor center and invasive front were correlated with histologic grade, and CD55-high tumor cells at invasive front with tumor, node and metastasis (TNM) stage (p<0.05). CD97-high stroma was correlated with lymph node metastasis (p=0.016) and TNM stage (p=0.030). CD97-high tumor cells at tumor center and invasive front were correlated with tumor size and CD97-high tumor cells at tumor center with tumor border (p<0.05). Patients with CD55-high stroma showed poor overall and recurrence-free survival (p<0.05) in univariate analysis, and were independently associated with short recurrence-free survival (p=0.025) in multivariate analysis. CONCLUSIONS: Stromal CD55 overexpression would be an indicator of adverse clinical outcome and a useful prognostic factor.

Prognostic Analysis in Colorectal Cancers Requiring Emergency Operations

Purpose: Emergency operative interventions for colorectal cancers are usually required in those patients with obstruction and perforation, even though they represent poor prognosis and low resectability. The purpose of this study is to evaluate clinical characteristics and survival rates of colorectal cancer patients with obstruction, perforation or both. METHODS: The clinical characteristics, resectabilities and survival rates of 433 patients with colorectal cancers who were operated on at the department of surgery, Hanyang University from March 1999 to March 2003 were retrospectively analyzed through medical records and telephone surveys. The patients were grouped as follows: Group1, without obstruction or perforation (n=387), Group2, with obstruction only (n=22), Group3, with perforation only (n=14) and Group4, with both complications (n=10). RESULTS: Patients with complications had higher operative mortality (group2: 9.1%, group3: 14.3%, group4: 10%) than those without complications (2.6%). Patients with perforation only (group 3) and with both complications (group 4) had poorer 5-year survival rates (group 3: 25%, group 4: 25%) than group1 (51.1%), however there was no statistical significance for the group with obstruction only. Conclusion: Colorectal cancer patients with perforation had poorer operative mortalities and survival rates, and the obstructed cases had poorer operative mortality. These poor prognosis appeared to be largely a function of more advanced stage of disease due to peritoneal seeding of cancer cells for the perforated cases and higher operative mortality because of other secondary complications for obstructed cases. Earlier diagnosis and prompt operative interventions should be attempted in those with suspected complications.

Relationships Between the Expressions of CDX1 and CDX2 mRNA and Clinicopathologic Features in Colorectal Cancers

BACKGROUND: CDX1 and CDX2 are members of the caudal-type homeobox gene family and control the proliferation and differentiation of intestinal mucosal cells. Their expressions are commonly reduced in colorectal cancer, but reports about the relationships between their expressions and clinicopathologic features are rare. The aim of this study was to examine the expressions of CDX1 and CDX2 mRNAs in colorectal cancers and to assess the relationships between their expressions and clinicopathologic features. METHODS: CDX1 and CDX2 mRNA expressions were analyzed by real-time polymerase chain reaction in 48 colorectal cancers and in adjacent non-tumorous normal mucosal tissue. RESULTS: CDX1 and CDX2 mRNA expressions were significantly reduced in colorectal cancer tissues versus normal mucosal tissues (p=0.001, p=0.042, respectively). As compared with paired normal mucosal tissues, colorectal tissues showed reduced CDX1 mRNA expression in 64.6% (31/48) and reduced CDX2 mRNA expression in 66.7% (32/48) of cases. A statistically significant positive correlation was found between the expressions of CDX1 mRNA and CDX2 mRNA in colorectal cancer (r=0.543, p< 0.001). However, the expressions of CDX1 and CDX2 mRNAs were not related to age, sex, cancer location, differentiation, lymphatic or vascular invasion, lymph node metastasis, stage or serum carcinoembryonic antigen level. CONCLUSIONS: CDX1 and CDX2 mRNA expressions were found to be significantly reduced in colorectal cancers, but these expressional changes were not found to be related to clinicopathologic features.

Relationship of CDX1 mRNA and CDX2 mRNA expression and clinicopathologic features in colorectal cancers / 대한내과학회지

BACKGROUND: CDX1 and CDX2, members of the caudal-type homeobox gene family, control proliferation and differentiation of intestinal mucosal cells. Their expression is reduced commonly in colorectal cancers, but reports about the relationship between their expression and the clinicopathologic features are rare. The aim of this study was to examine CDX1 mRNA and CDX2 mRNA expression in colorectal cancers and to assess the relationship between their expression and the clinicopathologic features. METHODS: CDX1 mRNA and CDX2 mRNA expression were analyzed by real-time polymerase chain reaction in 48 colorectal cancers and their adjacent non-tumorous normal mucosas. RESULTS: CDX1 mRNA and CDX2 mRNA expression were decreased significantly in colorectal cancers than in normal mucosas (p=0.001, p=0.042, respectively). In comparison with paired normal mucosas, colorectal cancers showed decreased CDX1 mRNA expression in 64.6% (31/48) and decreased CDX2 mRNA expression in 66.7% (32/48). There was a statistically significant correlation between CDX1 mRNA and CDX2 mRNA expression in colorectal cancers (r=0.543, p<0.001). CDX1 mRNA and CDX2 mRNA expression were not related to age, sex, location of cancer, differentiation, lymphatic or vascular invasion, lymph node metastasis, stage and serum carcinoembryonic antigen level in colorectal cancers. CONCLUSION: CDX1 mRNA and CDX2 mRNA expression were decreased significantly in colorectal cancers, but were not related to the clininopathologic features.

The expression of P53,K-ras and hMSH2 in ulcerative colitis-associated colorectal cancer / 中华消化杂志

0.05). The positive rate of MSI in UC with dysplasia was significantly higher than that in UC (P0.05). The loss of hMSH2 protein expression was not found in UC with dysplasia and UCACRC. Conclusions Both the mutations of P53, K-ras genes and MSI are early events in UCACRC. There is no relationship between MSI and loss of hMSH2 protein expression in (UCACRC).

Immediate effects of three different regimens in advanced colorectal cancers / 中国癌症杂志

0.05).Conclusions:There was no difference in terms of both effect and toxicity among the three regimens. All of them were effective and could be well tolerated by advanced colorectal cancer patients.