Prognosis Of Colorectal Carcinoma Research Articles

Rab11 collaborates E-cadherin to promote collective cell migration and indicates a poor prognosis in colorectal carcinoma.

Collective cell migration, whereby the cell-cell contacts such as E-cadherin are maintained during migration, has only recently emerged, and its detailed mechanisms are still unclear. In this study, the role of Rab11, which functions in recycling endosomes, and its relationship to E-cadherin in colorectal carcinoma were identified, and the role of Rab11 in the collective cell migration of colon cancer cells was clarified. A total of 107 patients with surgically resected colorectal carcinoma were enrolled in this immunohistochemical study. Relationships between the overexpression of Rab11 and E-cadherin and survival were evaluated. The cell biology of Rab11 overexpression or knock-down in HT-29 colon cells was studied. The expression of Rab11 and E-cadherin was not correlated with the stage of cancer or lymph node metastasis. However, the overall survival was poor in the group of 67 patients with duo-positive Rab11 and E-cadherin expression compared to the group (40 patients) without dual-positive expression (P = 0·038). Rab11 was demonstrated to have a physical interaction with E-cadherin, and overexpression of Rab11 was found to promote collective cell migration through the increased distribution of E-cadherin, which enhanced cell-cell connections. In addition, Rac1 activation and matrix metalloproteinase-2 expressions were upregulated upon Rab11 expression. This study demonstrated that Rab11 and E-cadherin expressions are indicators of poor survival time in colorectal carcinoma, but that Rab11 overexpression may contribute to increased collective cell invasion in colorectal carcinoma.

Dysregulation of MALAT1 and miR-619-5p as a prognostic indicator in advanced colorectal carcinoma.

The present study aimed to detect the expression of metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and microRNA (miR)-619-5p in colorectal carcinoma (CRC), and to evaluate the significance of MALAT1 and miR-619-5p expression in the clinical diagnosis and prognosis of CRC. Quantitative polymerase chain reaction was used to detect MALAT1 and miR-619-5p expression in 120 colorectal carcinoma and 120 adjacent normal tissue samples. The expression levels of MALAT1 and miR-619-5p were significantly different between colorectal carcinoma and adjacent normal tissues (P<0.05). MALAT1 exhibited an average 2.52-fold increase in colorectal adenoma when compared with adjacent normal tissues, while miR-619-5p exhibited an average 5.79-fold decrease in colorectal adenoma when compared with adjacent normal tissues. There was a significant difference between the MALAT1 expression in CRC tissues obtained from men and women (P=0.027), and in tumor-node-metastasis (TNM) stage II and stage III lesions (P=0.019). MALAT1 expression was associated with lymphovascular invasion (P=0.047) and perineural invasion (P=0.012). In addition, miR-619-5p expression was also significantly different between men and women (P=0.032), and between TNM stage II and stage III lesions (P=0.012). miR-619-5p expression was also associated with lymphovascular invasion (P=0.023) and perineural invasion (P=0.009). Patients with high expression of MALAT1 and low expression of miR-619-5p demonstrated significantly shorter disease-free survival (DFS) (P=0.002) and overall survival (OS) times (P=0.004) compared with patients with low MALAT1 expression and high miR-619-5p expression. Patients with perineural invasion demonstrated significantly shorter DFS (P=0.001) and OS times (P=0.003) compared with patients without perineural invasion. In addition, there was a negative correlation between MALAT1 expression and miR-619-5p expression (r=-0.415, P=0.004) in CRC tissues. In conclusion, MALAT1 and miR-619-5p have potential for the molecular diagnosis of CRC patients, and combined assaying of MALAT1 and miR-619-5p may improve the accuracy of the diagnosis of CRC and act as a good prognostic indicator in CRC patients.

Molecular profile of 5-fluorouracil pathway genes in colorectal carcinoma

BackgroundThis study addresses involvement of major 5-fluorouracil (5-FU) pathway genes in the prognosis of colorectal carcinoma patients.MethodsTesting set and two validation sets comprising paired tumor and adjacent mucosa tissue samples from 151 patients were used for transcript profiling of 15 5-FU pathway genes by quantitative real-time PCR and DNA methylation profiling by high resolution melting analysis. Intratumoral molecular profiles were correlated with clinical data of patients. Protein levels of two most relevant candidate markers were assessed by immunoblotting.ResultsDownregulation of DPYD and upregulation of PPAT, UMPS, RRM2, and SLC29A1 transcripts were found in tumors compared to adjacent mucosa in testing and validation sets of patients. Low RRM2 transcript level significantly associated with poor response to the first-line palliative 5-FU-based chemotherapy in the testing set and with poor disease-free interval of patients in the validation set irrespective of 5-FU treatment. UPP2 was strongly methylated while its transcript absent in both tumors and adjacent mucosa. DPYS methylation level was significantly higher in tumor tissues compared to adjacent mucosa samples. Low intratumoral level of UPB1 methylation was prognostic for poor disease-free interval of the patients (P = 0.0002). The rest of the studied 5-FU genes were not methylated in tumors or adjacent mucosa.ConclusionsThe observed overexpression of several 5-FU activating genes and DPYD downregulation deduce that chemotherapy naïve colorectal tumors share favorable gene expression profile for 5-FU therapy. Low RRM2 transcript and UPB1 methylation levels present separate poor prognosis factors for colorectal carcinoma patients and should be further investigated.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2826-8) contains supplementary material, which is available to authorized users.

Association between prognostic survival of human colorectal carcinoma and ZNRF3 expression.

PurposeE3 ubiquitin ligase ZNRF3 is linked to the pathogenesis of diseases and tumorigenesis. The present study aims to explore the expression of ZNRF3 and its association with prognostic survival of human colorectal carcinoma.MethodsA follow-up survey of 168 patients with colorectal carcinoma was performed, and specimens of colorectal tissues were collected for immunohistochemistry and Western blotting analyses. Furthermore, overexpression of ZNRF3 using transient transfection with the recombinant pEGFP-ZNRF3 plasmid and detection of apoptosis and proliferation were performed in HCT-116 cells.ResultsThe results showed a diverse feature of ZNRF3 staining, such as strong, moderate, weak, or negative, in colorectal carcinoma tissues. Interestingly, univariate Kaplan–Meier analysis showed that cases with strong or moderate expression of ZNRF3 showed an optimistic disease-free survival and overall survival compared with negative expression of ZNRF3, and multivariate Cox model demonstrated ZNRF3 as an independent prediction index for overall survival and disease-free survival. In vitro, the overexpression of ZNRF3 was related to the negative regulation of Wnt/β-catenin pathway and referred to an induction of apoptosis and suppression of proliferation in ZNRF3-transfected HCT-116 cells.ConclusionOur results suggest that the higher expression of ZNRF3 acts as a novel marker of indicating the optimistic prognosis of colorectal carcinoma by suppressing cancer cell growth and facilitating apoptosis.

Reduced expression of EphA5 is associated with lymph node metastasis, advanced TNM stage, and poor prognosis in colorectal carcinoma.

Colorectal carcinoma (CRC) is the third most common cancer and a major cause of morbidity and mortality throughout the world. The prognosis of patients has improved markedly over the last 15 years because of the introduction of new therapy including molecular target drugs. To comprehensively understand the molecular process of carcinogenesis of colorectal carcinoma is essential for the diagnosis, prognosis and treatment. EphA5 is a member of the Eph family and plays a critical role in carcinogenesis of lung cancer, prostate cancer, and breast cancer. The expression profile and the role of EphA5 in colorectal carcinoma have not been well investigated till now. In this study, a set of colorectal carcinoma specimens was subjected to immunohistochemical assay using an EphA5 specific antibody. The relationship between the expression of EphA5 and clinicopathological parameters was statistically analyzed. EphA5 was positively expressed in all tested normal mucosa specimens (120/120, 100%) and partly in colorectal carcinoma specimens (70/120, 58.3%). The loss of EphA5 protein was associated with depth of wall invasion (P=0.002), poor tumor differentiation (P<0.001), lymph node metastasis (P<0.001), and advanced TNM stage (P<0.001). The survival analysis showed that patients with reduced expression of EphA5 had a poor overall survival (P=0.017). Our data indicate that EphA5 receptor may be a tumor suppressor in colorectal carcinoma and it may be a new therapeutic target for colorectal carcinoma.

Overexpression of CHKA contributes to tumor progression and metastasis and predicts poor prognosis in colorectal carcinoma.

Aberrant expression of choline kinase alpha (CHKA) has been reported in a variety of human malignancies including colorectal carcinoma (CRC). However, the role of CHKA in the progression and prognosis of CRC remains unknown. In this study, we found that CHKA was frequently upregulated in CRC clinical samples and CRC-derived cell lines and was significantly correlated with lymph node metastasis (p = 0.028), TNM stage (p = 0.009), disease recurrence (p = 0.004) and death (p < 0.001). Survival analyses indicated that patients with higher CHKA expression had a significantly shorter disease-free survival (DFS) and disease-specific survival (DSS) than those with lower CHKA expression. Multivariate analyses confirmed that increased CHKA expression was an independent unfavorable prognostic factor for CRC patients. In addition, combination of CHKA with TNM stage was a more powerful predictor of poor prognosis than either parameter alone. Functional study demonstrated that knockdown of CHKA expression profoundly suppressed the growth and metastasis of CRC cells both in vitro and in vivo. Mechanistic investigation revealed that EGFR/PI3K/AKT pathway was essential for mediating CHKA function. In conclusion, our results provide the first evidence that CHKA contributes to tumor progression and metastasis and may serve as a novel prognostic biomarker and potential therapeutic target in CRC.

The association of HMGB1 expression with clinicopathological significance and prognosis in Asian patients with colorectal carcinoma: a meta-analysis and literature review.

BackgroundThe association of high mobility group box 1 (HMGB1) expression with clinicopathological significance and prognosis in Asian patients with colorectal carcinoma (CRC) remains controversial. The purpose of this study was to conduct a meta-analysis and literature review to identify the role of HMGB1 in the development and prognosis of CRC in Asians.MethodsAll eligible studies regarding the association between HMGB1 expression in tissue with clinicopathological significance and prognosis in Asian patients with CRC published up to January 2015 were identified by searching PubMed, Web of Science, Chinese National Knowledge Infrastructure, and WanFang database. Analysis of pooled data was performed, while odds ratio (OR) or hazard radio with 95% confidence interval (CI) was calculated and summarized to evaluate the strength of this association in fixed- or random-effects model.ResultsThe expression level of HMGB1 in CRC tissues was much higher than normal colorectal tissues (OR =27.35, 95% CI 9.32–80.26, P<0.0001) and para-tumor colorectal tissues (OR =10.06, 95% CI 4.61–21.95, P<0.0001). There was no relation between the HMGB1 expression and sex, age, clinical T stage, tumor size, and location (colon or rectum cancer). However, a significant relation was detected between the HMGB1 expression and clinical stage (American Joint Committee on Cancer 7), lymph node metastasis, distant metastasis, tumor invasion depth, and differentiation rate (P=0.002, P≤0.0001, P<0.0001, P<0.0001, and P=0.007, respectively). Patients with higher HMGB1 expression had shorter overall survival time, whereas patients with lower level of HMGB1 had better survival (hazard ratio =1.40, 95% CI 0.98–1.82, P<0.0001).ConclusionIn this meta-analysis, our results illustrated the significant relationship of HMGB1 protein overexpression in tissues with clinicopathological characteristics and prognosis of CRC. Thus, HMGB1 may be a promising marker in predicting the clinical outcome of patients with CRC. However, more well-designed studies of large sample size are warranted to validate the findings of current study.

Abstract 1544: Overexpression of Rab11 and E-cadherin promotes collective cell migration and indicates a poor prognosis in colorectal carcinoma

Abstract Collective cell migration, whereby the cell-cell contacts such as E-cadherin are maintained during migration, has recently emerged, and the detailed mechanisms of this process are still unclear. The present study identified the role of Rab11 which functions in recycling endosome and the relation to E-cadherin in colorectal carcinoma and clarified the mechanism of Rab11 in the collective cell migration of cancer cells. The relationships between the overexpression of Rab11 and E-cadherin and survival were evaluated from colorectal carcinoma patients. A total of 107 patients with surgically resected colorectal carcinoma were enrolled in immunohistochemical study. The relationships between the overexpression of Rab11 and E-cadherin and survival were evaluated. GFP tagged Rab11 or Rab11 shRNA was introduced into HT-29 colon cancer cells for overexpression or knockdown. The interaction between E-cadherin and Rab11 was determined by immunoprecipitation. Rac1 and matrix metalloproteinase (MMP) activities were evaluated as functional effectors of collective cell migration. In the results, the expression of Rab11 and E-cadherin was not correlated with the stages of cancer or lymph node metastasis. However, the overall survival was poor in the group of 60 patients with duo-positive Rab11 and E-cadherin expression compared to the group (47 patients) without duo-positive expression (p = 0.038). In the cell biology assay, Rab11 was demonstrated through its physical interaction with E-cadherin, and overexpression of Rab11 was found to promote collective cell migration through the increased distribution of E-cadherin, which enhanced cell-cell connections. In addition, Rac1 activation and MMP2 expression were up-regulated upon Rab11 expression. This study demonstrated that Rab11and E-cadherin expression are poor indicators of survival time in colorectal carcinoma, but that Rab11 overexpression may contribute to increased collective cell invasion in colorectal carcinoma. Citation Format: Yuan-Chiang Chung, Wan-Chen Wei, Chia-Nung Hung, Chih-Ping Hsu, Hsiang-Ling Chiu, King-Jen Chang, Wei-Ting Chao. Overexpression of Rab11 and E-cadherin promotes collective cell migration and indicates a poor prognosis in colorectal carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1544.

Lack of AMACR Immunostaining is an Independent Predictor of Poor Prognosis in Colorectal Carcinoma

Background: AMACR (Alfa-Methylacyl-CoA Racemase) overexpression has become a useful biomarker of prostate cancer. In the present cohort we are aiming to analyse AMACR immunostaining in normal colonic mucosa, colorectal adenoma, and colorectal carcinoma (CRC) to explore the significance of immune-staining in relation to clinic-pathological features, prognosis, and survival. Materials and Methods: The study included 38 normal colonic mucosae, 40 colorectal adenomas, 196 CRC, and 49 associated lymph node metastasis. Tissue microarrays were designed and constructed and immunostaining was done using anti-AMACR antibody. Results: AMACR was absent in normal colonic mucosa while it showed positive immunostaining in 47.5% of adenomas, 53.6% colorectal carcinomas and 36.7% of nodal metastasis. There was no statistically significant difference between AMACR immunostaining in primary CRC in relation adenomas, and nodal metastasis. Low AMACR immunostaining showed significant association with the occurrence nodal metastasis (p=0.039) and distant metastasis (p=0.022). There was no significant association between AMACR immune-staining and other clinic pathological parameters. Regression analysis revealed that reduced AMACR immunostaining was an independent predictor of positive surgical resection margins, presence of Lymph vascular invasion, distant metastasis, and lymph node metastasis. AMACR immunostaining was not related to both diseases free survival and overall survival. Conclusion: AMACR immune-staining correlated with nodal metastasis and distant metastasis. Loss of immunostaining of AMACR is an independent predictor of lymph vascular invasion, positive surgical margin, nodal and distant metastasis. AMACR may serve as biomarker of progression and prognosis of CRC.

Prognostic Value of Immunohistochemical Expressions of the Stem Cell Biomarker &amp;quot;LGR5&amp;quot; and the Proliferation Biomarker &amp;quot;TPX2&amp;quot; in Colorectal Carcinoma

Aim: Colorectal carcinoma (CRC) is the commonest and most deathly malignant gastrointestinal tumors. Carcinogenic process starts in a group of cancer cells, called cancer stem cells (CSCs) having the ability to start and maintain tumor growth and invasion. In order to detect and remove colon CSCs, a selective biomarker (leucine-rich-repeat-containing G-protein-coupled receptor 5) might be required. At the same time, an abnormal expression of TPX2 (targeting protein for xenopus kinesin-like protein 2) has been found to be related to the development and progression of tumors. We aimed to evaluate the immunohistochemical expressions of LGR5 and TPX2 in CRC in a trial to clarify their relations to proliferation and metastasis of CRC, and hence its prognosis. Methods: Immunohistochemical staining of both LGR5 and TPX2 was assessed in sections from sixty paraffin blocks of CRC . The relationships between their levels of expressions with the clinicopathological parameters and patient outcome were statistically analyzed. Results: The immunoexpression of LGR5 in CRC was signifi­cantly positively correlated with location of the tumor, grade, stage, local recurrence, lymph node and distant metastasis (p <0.001). The expression of TPX2 in CRC was also found to be signifi­cantly correlated with the previous parameters (p <0.001). High LGR5 and TPX2 immunohistochemical expressions were strongly correlated with worse 3-year overall survival (OS), local recurrence free survival (LRFS) and distant metastases free survival (DMFS) (P <0.001). Conclusion: High immunohistochemical expressions of both LGR5 and TPX2 and the positive correlation between both of them represent signs of poor prognosis of CRC.

Upregulation of NETO2 expression correlates with tumor progression and poor prognosis in colorectal carcinoma.

BackgroundNeuropilin and tolloid-like 2 (NETO2) has been found to be overexpressed in different human cancers, but its expression pattern and clinical relevance in colorectal carcinoma (CRC) remains unknown.MethodsReal-time quantitative PCR, western blot and immunohistochemistry analyses were used to analyze the expression of NETO2 in CRC clinical samples. The correlation of NETO2 expression with clinicopathologic features was estimated in a cohort containing 292 patients with primary CRC. Kaplan-Meier and Cox proportional hazards regression analyses were used to assess the prognostic value of NETO2 expression in CRC.ResultsThe expression of NETO2 was frequently upregulated in CRC clinical samples at both the mRNA and protein levels, and its upregulation was significantly correlated with poor tumor differentiation (p = 0.013), advanced local invasion (p = 0.049), increased lymph node metastasis (p = 0.009), advanced TNM stage (p = 0.041) and increased patient death (p = 0.001). Kaplan-Meier analysis of the complete study cohort revealed that patients with high-NETO2 tumors had a significantly shorter disease-specific survival (DSS) than those with low-NETO2 tumors (p < 0.001). Importantly, high levels of NETO2 protein predicted poor DSS for patients with early stage tumors (p = 0.027) and for those with advanced stage tumors (p = 0.020). Furthermore, multivariate analyses indicated that increased NETO2 expression was an independent unfavorable prognostic factor for patients with early stage tumors (hazard ratio [HR] = 1.937, 95 % CI = 1.107-3.390, p = 0.021) as well as patients with advanced stage tumors (HR = 2.241, 95 % CI = 1.245-4.035, p = 0.007).ConclusionsOur findings suggest that NETO2 upregulation could serve as a potential biomarker for the prediction of advanced tumor progression and unfavorable prognosis in patients with CRC.

181P Determinants of colorectal carcinoma prognosis: role of CEA status, dietary habit and microsatellite instability

181P Determinants of colorectal carcinoma prognosis: role of CEA status, dietary habit and microsatellite instability

Periostin expression in intra-tumoral stromal cells is prognostic and predictive for colorectal carcinoma via creating a cancer-supportive niche.

Periostin (POSTN) expression in cancer cells and circulation has been related to poor prognosis of colorectal carcinoma (CRC). However, the role of POSTN expressed in intra-tumoral stroma on CRC progression remains largely unknown. This study enrolled 1098 CRC patients who received surgical treatment in Shanghai and Guangzhou, Mainland China. In Shanghai cohort, immunohistochemistry score of stromal POSTN expression increased consecutively from adjacent mucosa, primary CRC tissues, to metastatic CRC tissues (P < 0.001), while medium- and high-stromal POSTN expression, rather than epithelial POSTN expression, independently predicted unfavorable prognoses of CRC, adjusted for covariates including TNM stage and postoperative chemotherapy in multivariate Cox models. The results in Shanghai cohort were faithfully replicated in Guangzhou cohort. Stromal POSTN expression dose-dependently predicted an unfavorable prognosis of stage III CRC patients with postoperative chemotherapy in both cohorts. POSTN derived from colonic fibroblasts or recombinant POSTN significantly promoted proliferation, anchorage independent growth, invasion, and chemo-resistance of CRC cells; whereas these effects were counteracted via targeting to PI3K/Akt or Wnt/β-catenin signaling pathway. CRC cell RKO-derived factor(s) significantly induced POSTN production in colonic fibroblasts and autocrine POSTN promoted proliferation, migration, and anchorage independent growth of fibroblasts. Conclusively, stromal POSTN is prognostic and predictive for CRC via creating a niche to facilitate cancer progression. Targeting POSTN-induced signaling pathways may be therapeutic options for metastatic or chemoresistant CRC.

Clinicopathologic, molecular, and prognostic implications of the loss of EPCAM expression in colorectal carcinoma.

We aimed to comprehensively investigate the clinicopathologic and molecular implications of altered epithelial cell adhesion molecule (EPCAM) expression in colorectal carcinoma (CRC). EPCAM immunohistochemical expression, EPCAM 3′ end deletion, EPCAM promoter methylation, microsatellite instability (MSI), and the CpG island methylator phenotype (CIMP) were analyzed in large cohorts of human CRCs. Among 218 MSI-high CRCs, complete loss (CL) of EPCAM expression was observed in two cases, both of which displayed MSH2 deficiency and EPCAM 3′ deletion. Thirty-one of the 218 MSI-high CRCs demonstrated the partial loss (PL) of EPCAM expression without EPCAM deletion or methylation and were correlated with CIMP-high and poor disease-free survival. Histologically, foci exhibiting EPCAM loss in EPCAM-PL tumors were dominantly distributed in poorly differentiated tumor components and/or in the invasive tumor front. The implications of EPCAM-PL were further validated in a consecutive series of 726 CRCs. EPCAM-PL (n = 50; 6.9%) was also associated with CIMP-high and adverse pathologic factors and was confirmed to be an independent poor prognostic factor in CRC (HR, 1.57; 95% CI, 1.04 to 2.39). EPCAM-CL can be used to screen for EPCAM deletion-induced Lynch syndrome-associated CRC, whereas EPCAM-PL can be used as an indicator of tumor aggressiveness and poor prognosis in CRC.

The Association of HMGB1 Expression With Clinicopathological Significance and Prognosis in Colorectal Carcinoma: A Meta-Analysis and Literature Review

The Association of HMGB1 Expression With Clinicopathological Significance and Prognosis in Colorectal Carcinoma: A Meta-Analysis and Literature Review

Evaluation of the correlation of KAI1/CD82, CD44, MMP7 and β-catenin in the prediction of prognosis and metastasis in colorectal carcinoma.

BackgroundTo investigate the relationship of KAI1/CD82, CD44, matrix metalloproteinase 7 (MMP7) and β-catenin, and examine its association with clinicopathological features, metastasis and prognosis in colorectal carcinoma (CRC).MethodsImmunohistochemical (IHC) analysis was used to detect the expression of KAI1/CD82, CD44, MMP7 and β-catenin in 174 archival surgical specimens of human CRC. Furthermore, clinicopathological features such as age, sex and so on were also collected retrospectively.ResultsCD44, MMP7 and β-catenin expression was positively associated with distant metastasis, lymph node metastasis and tumor-node-metastasis (TNM) stage. However, decreased KAI1/CD82 expression correlated significantly with distant metastasis, lymph node metastasis and TNM stage. KAI1/CD82 expression showed a negative correlation with CD44, MMP7 and β-catenin. Furthermore, β-catenin expression showed a positive correlation with CD44 and MMP7. Multivariate logistic regression analysis showed that KAI1/CD82 and β-catenin expression were significantly associated with lymph node metastasis and KAI1/CD82 was significantly associated with distant metastasis. Kaplan-Meier analysis revealed that CD44, MMP7 and β-catenin expression was negatively correlated with overall survival (OS), while KAI1/CD82 expression was positively correlated with OS. Low KAI1/CD82 expression and high expression of CD44, MMP7 and β-catenin was associated with a poor prognosis in CRC. Multivariate Cox regression analysis indicated that the expression of KAI1/CD82, MMP7 and β-catenin were independent predictors of OS in CRC.ConclusionThe expression of KAI1/CD82, CD44, MMP7 and β-catenin is related to tumor metastasis and prognosis in CRC. Combined detection of these factors may be of significant value in predicting the prognosis and metastasis in CRC patients.

Distribution of single metastasized lymph nodes and its significance in the prognosis of colorectal carcinoma

Distribution of single metastasized lymph nodes and its significance in the prognosis of colorectal carcinoma

P-202 Molecular confocal laser endomicroscopy (CLE) for the assessment of prognosis in colorectal carcinoma, based on evaluation of putative cancer stem cell markers

P-202 Molecular confocal laser endomicroscopy (CLE) for the assessment of prognosis in colorectal carcinoma, based on evaluation of putative cancer stem cell markers

Expression and clinical significance of mammalian target of rapamycin/P70 ribosomal protein S6 kinase signaling pathway in human colorectal carcinoma tissue.

The activation of mammalian target of rapamycin (mTOR) has been reported in tumor development, but the role of mTOR in colorectal carcinomas remains unclear. The aim of the present study was to investigate the significance of mTOR and its downstream effector 70 kDa ribosomal protein S6 kinase (P70S6K) in human colorectal carcinomas. The phosphorylated (p-)mTOR and p-P70S6K proteins were examined by immunohistochemistry performed on tissue microarray containing tissue samples obtained from colorectal carcinoma (n=111), adenomatous polyps (n=40) and normal colonic mucosa (n=40), with a comparison between the expression of these proteins and the clinicopathological parameters of patients with carcinomas. The positive expression rates of p-mTOR and p-P70S6k were 60.4 and 65.8%, respectively, in colorectal carcinoma tissue, which was significantly increased compared with the tissue from adenomatous polyps (27.5 and 20%, respectively) and normal colonic mucosa (10.0 and 5.0%, respectively) (P<0.05). Overexpression of the p-mTOR and p-P70S6K proteins was significantly associated with the tumor-node-metastasis stage, the occurrence of distal and lymph node metastasis and the degree of differentiation. Aberrant expression of p-mTOR and p-P70S6K may contribute to the pathogenesis, growth, invasion and metastasis of colorectal carcinoma. The phosphorylation of these proteins was considered to be a promising marker to indicate the aggressive behaviors and prognosis of colorectal carcinomas. The overexpression of the mTOR/P70S6K signaling pathway may play an important role in colorectal carcinoma carcinogenesis. The expression of p-mTOR and p-P70S6K was considered as a promising marker to indicate the aggressive behaviors and prognosis of human colorectal carcinomas.

Image analyzer-based assessment of tumor-infiltrating T cell subsets and their prognostic values in colorectal carcinomas.

To find useful tools to evaluate the prognosis in colorectal carcinoma (CRC) patients, we investigated the prognostic values of tumor-infiltrating T lymphocyte subsets according to intratumoral subsites as well as clinical or molecular characteristics. Immunohistochemistry for CD8, CD45RO, and FOXP3 was performed, and densities of the T cell subsets in each tissue microarray core (cells/mm2) were measured by image analysis. In the training set (n = 218) of CRC, T cell subset densities in the invasion front were more strongly associated with patient outcome than those in the tumor center. In the validation set (n = 549), T cell subset densities in the invasion front were evaluated. Univariate analysis showed that all three T cell subset densities were significantly associated with longer progression free survival and overall survival time (p < 0.001). In multivariate analysis, a high CD45RO density correlated independently with longer progression free survival (p = 0.011) and overall survival time (p = 0.007) in CRC patients, regardless of tumor location or adjuvant chemotherapy status. Our results showed that CD45RO density in the invasion front was the only independent prognostic factor regarding CRC. However, CD8 and FOXP3 densities were also independent prognostic factors in certain clinical settings. Thus, image analysis of tissue microarray cores in the invasion front of CRC could be used as a valid method for evaluating the prognostic significance of T cell subset densities.