Prognosis Of Colorectal Carcinoma Research Articles

Prognostic value of carbonic anhydrase VII expression in colorectal carcinoma

BackgroundCarbonic anhydrases (CAs) have been implicated in the pathogenesis of human cancers. Carbonic anhydrase VII (CA7), a member of the CA gene family, was recently demonstrated to be expressed in several human tissues including colon. Nevertheless, the expression and clinical relevance of CA7 in colorectal carcinoma (CRC) has not been investigated.MethodsReal-time PCR, western blot, and immunohistochemistry analyses were used to determine CA7 expression in CRC clinical samples. The correlation of CA7 expression with clinicopathologic features was assessed in 228 patients from Luoyang, China (training cohort) and validated in 151 patients from Shanghai, China (validation cohort). Kaplan-Meier and Cox proportional regression analyses were used to estimate the association between CA7 expression and patients’ survival.ResultsCA7 expression was frequently downregulated in CRC tissues at both the mRNA and protein levels. Reduced expression of CA7 was significantly correlated with poor differentiation, positive lymph node metastasis, advanced TNM stage and unfavorable clinical outcome not only in the training cohort but also in the validation set. Survival analysis indicated that patients with lower CA7 expression had a significantly shorter disease-specific survival (DSS) than those with higher CA7 expression. Importantly, further stage-based analyses revealed that decreased CA7 expression significantly predicted poor DSS and was an independent adverse prognostic indicator for patients with early stage tumors in both cohorts.ConclusionsOur results indicate that decreased expression of CA7 correlates with disease progression and predicts poor prognosis in CRC, especially for patients with early stage tumors.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1216-y) contains supplementary material, which is available to authorized users.

Assessment of Tumor Invasion Depth in Colorectal Carcinoma Using Multiphoton Microscopy

Assessment of tumor invasion depth prior to making therapeutic decisions in colorectal carcinoma is crucial for both the patient and the physician. In this paper, multiphoton microscopy (MPM) was used to simultaneously label freely image loose areolar connective tissue in the submucosa and intramuscular septa in the muscularis propria to perform assessment of colorectal carcinoma invasion depth. The results indicated that MPM can accurately exhibit whether colorectal carcinoma invades into the submucosa or the muscularis propria. Collagen content alteration and the presence of dirty necrosis can be extracted to serve as quantitatively intrinsic biomarkers for reflecting collagen degradation, the occurrence of desmoplastic reaction, and breakdown of cancer cells, which are tightly related to the prognosis of colorectal carcinoma. With the development and clinical applications of the multiphoton endoscope, in vivo histological-like diagnosis of tumor invasion depth may become its main application in the field of colorectal carcinoma and lead to faster and improved therapeutic decision making in the clinics.

Intestinal obstruction: predictor of poor prognosis in colorectal carcinoma?

OBJECTIVES:The goal of this study was to assess the relationship between intestinal obstruction and the prognosis of colorectal carcinoma.METHODS:Data pertaining to 4,501 colorectal carcinoma patients were extracted from the national colorectal registry and analysed. Survival analysis was performed using the Kaplan-Meier method. The log-rank test was used to compare the survival rate between patients with intestinal obstruction and those without intestinal obstruction. The p-values<0.05 were considered to indicate statistical significance. Simple Cox proportional hazards regression analysis was used to estimate the crude hazard ratio of mortality from colorectal cancer.RESULTS:Intestinal obstruction was reported in more than 13% of patients. The 3-year survival rate after treatment was 48.3% (95% confidence interval [CI], 43.9 to 52.8) for patients with intestinal obstruction (n=593) and 54.9% (95% CI, 53.1 to 56.6) for patients without intestinal obstruction (n=3,908). The 5-year survival rate for patients with intestinal obstruction was 37.3% (95% CI, 31.9 to 42.8), which was lower than that of patients without intestinal obstruction (45.6%; 95% CI, 43.5 to 47.7). After adjusting the hazard ratio for other prognostic variables, intestinal obstruction had a statistically significant negative correlation with the survival rate of colorectal cancer patients, with an adjusted hazard ratio of 1.22 (p=0.008).CONCLUSIONS:The presence of intestinal obstruction is associated with a lower survival rate among colorectal cancer patients.

Increased expression of formin-like 3 contributes to metastasis and poor prognosis in colorectal carcinoma

Formin-like 3 (FMNL3), a member of diaphanous-related formins subfamily, plays an important role in cytoskeleton reorganization, cell adhesion and cancer cell invasion in vitro. This study aimed to explore the expression of FMNL3 in colorectal carcinoma (CRC) cell-lines and tissues, and further evaluate its prognostic value and correlation with the clinicopathological parameters, and also investigate the effects of FMNL3 gene silencing on the growth and metastasis of CRC in vivo. Immunohistochemical analysis showed that FMNL3 protein was distributed in a punctuate aggregation pattern and located mainly in the cytoplasm of glandular cavity side, close to the nucleus of CRC cells. The positive rate of FMNL3 expression was 87.5% (84/96) in CRC, which was significantly higher than that in adjacent normal mucosa (30%, 9/30). Moreover, FMNL3 protein expressed far more in primary CRC with metastasis and corresponding lymph nodes metastatic CRC than in primary CRC without metastasis. Increased expression of FMNL3 was closely correlated with tumor size, differentiation, serosal invasion, and both lymph node metastasis and distant metastasis. However, it was not correlated with patients' age and gender. According to Kaplan–Meier survival analyses, patients with FMNL3 high expression level had lower overall survival rate than that with FMNL3 low expression level. Univariate and multivariate analyses revealed that high FMNL3 expression was a significant and independent prognostic predictor of patients with CRC. In addition, FMNL3 mRNA and protein levels were substantially up-regulated in CRC-metastasis-derived cell lines, as compared to those in primary-CRC-derived ones. FMNL3 gene silencing suppressed the growth and metastasis of CRC in vivo. In conclusion, FMNL3 plays an important role in the progression and metastasis of CRC and may be a novel potential prognostic predictor and therapeutic target for patients with CRC.

Sensitive and simultaneous determination of 5-methylcytosine and its oxidation products in genomic DNA by chemical derivatization coupled with liquid chromatography-tandem mass spectrometry analysis.

Cytosine methylation (5-methylcytosine, 5-mC) in genomic DNA is an important epigenetic mark that has regulatory roles in diverse biological processes. 5-mC can be oxidized stepwise by the ten-eleven translocation (TET) proteins to form 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-foC), and 5-carboxylcytosine (5-caC), which constitutes the active DNA demethylation pathway in mammals. Owing to the extremely limited contents of endogenous 5-mC oxidation products, no reported method can directly determine all these cytosine modifications simultaneously. In the current study, we developed selective derivatization of cytosine moieties with 2-bromo-1-(4-dimethylamino-phenyl)-ethanone (BDAPE) coupled with liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) for the simultaneous determination of these cytosine modifications in genomic DNA. The chemical derivatization notably improved the liquid chromatography separation and dramatically increased detection sensitivities of these cytosine modifications. The limits of detection (LODs) of the derivatives of 5-mC, 5-hmC, 5-foC, and 5-caC were 0.10, 0.06, 0.11, and 0.23 fmol, respectively. Using this method, we successfully quantified 5-mC, 5-hmC, 5-foC, and 5-caC in genomic DNA from human colorectal carcinoma (CRC) tissues and tumor-adjacent normal tissues. The results demonstrated significant depletion of 5-hmC, 5-foC, and 5-caC in tumor tissues compared to tumor-adjacent normal tissues, and the depletion of 5-hmC, 5-foC, and 5-caC may be a general feature of CRC; these cytosine modifications could serve as potential biomarkers for the early detection and prognosis of CRC. Moreover, the marked depletion of 5-hmC, 5-foC, and 5-caC may also have profound effects on epigenetic regulation in the development and formation of CRC.

Semaphorin 4D and hypoxia-inducible factor-1α overexpression is related to prognosis in colorectal carcinoma.

To investigate semaphorin 4D (Sema4D) and hypoxia-inducible factor-1α (HIF-1α) expression in colorectal carcinoma and evaluate their clinicopathological and prognostic significance. Eighty-six curatively resected colorectal carcinoma patients at different stages of disease were randomly selected from the group of patients who underwent surgery, and none of them received preoperative radiochemotherapy. Normal proximal adjacent bowel tissue, which served as an internal control, was obtained from 52 randomly selected patients. Immunohistochemistry was performed to analyze the expression of Sema4D and the tumor angiogenesis-related protein HIF-1α in normal colorectal tissues and colorectal carcinoma tissues. The relationships between the expression and clinical characters and prognosis were analyzed. HIF-1α and Sema4D were positively expressed in 58% and 60% of colorectal carcinoma tissues, respectively. Significantly lower expression levels were observed in normal mucosa (8% and 12%, respectively). HIF-1α and Sema4D expression was closely correlated with histological tumor type, tumor-node-metastasis (TNM) stage, and lymphatic metastasis (P<0.05), but not with age or tumor size (P>0.05). HIF-1α and Sema4D protein expression was significantly correlated with prognosis of colorectal carcinoma, as determined by Spearman rank correlation analysis (r=0.567; P<0.01). Multivariate Cox analysis revealed that only Sema4D expression played a significant role in predicting patient prognosis (P<0.05). These findings suggest that HIF-1α and Sema4D expression correlates with histological tumor type, TNM stage, and lymphatic metastasis in colorectal carcinoma and that Sema4D is a prognostic indicator of colorectal carcinoma.

Characterization of HER2 Gene/Protein and Ki67 Protein Expressions in Colorectal Carcinoma Variants With Relation To Clinicopathological Parameters and Prognosis: An Immunohistochemical and Fluorescence In Situ Hybridization Study

Objective The data on the frequency and pattern of HER2 expression in colorectal carcinoma (CRC) and its clinical signifi¬cance are ambiguous. In addition, little is known about HER2 status in CRC variants and its relation with proliferative activity and clinical outcome. Such knowledge may be of potential value for therapeutic decision making in CRCs. Methods The HER2 gene/protein status was assessed by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in a tissue microarray of 150 CRCs and correlated with the expression of the proliferation marker Ki67, clinicopathological factors, and prognosis. Results CRCs were categorized into conventional adenocarcinoma (CA), 47 cases; adenocarcinoma with mucinous component (AMC), 28 cases; mucinous adenocarcinoma (MA), 56 cases; and signet ring cell carcinoma (SRCC), 19 cases. Compared to other variants, CA was significantly associated with favorable clinicopathological features, higher overall survival (OS) and disease-free survival (DFS), while SRCC and MA were significantly associated with ominous clinicopathological features, lower OS and DFS. Cytoplasmic HER2 overexpression was detected in 14.2% of CRC cases and showed a significant agreement with gene amplification. HER2 overexpression was significantly associated with favorable clinicopathological features notably early stages. High Ki67 expression was detected in 48% of CRC cases. HER2 and Ki67 were significantly different among CRC variants with AMC showing the greatest frequency of HER2 overexpression and Ki67 high expression than the other variants. The interrelation between HER2 and Ki67 expression was statistically insignificant and neither had any significant relation to OS or DFS in any of the CRC variants. Conclusions We conclude that mucinous histology infers an adverse prognosis in CRC. A subset of early stage CRC patients, with HER2 overexpression and possibly a distinct variant, may benefit from HER2 targeted therapy. IHC can be used as a method for screening of HER2 gene amplification in CRCs.

Abstract 4176: Identifying analytes associated with poor prognosis in CRC

Abstract Cancer patients with undetectable micrometastases at the time of diagnosis are in danger of subsequent metastatic growth that worsens their outcome. Therefore, identification of these patients with latent metastases could reduce morbidity and mortality by helping physicians to choose whether to treat with an adjuvant therapy. In colorectal carcinoma (CRC), 20-30% of stage II patients will have a recurrence at a distant site after removal of the primary tumor. In order for cancer cells to metastasize, they must switch to an “invasive phenotype”. To identify molecular changes in cancer that drive invasion, our laboratory previously built a molecular network model of invasive subcellular structures termed invadopodia. Centrality and random walk analyses identified candidate signaling hubs that may control invadopodia formation or activity. To identify which of these hubs control invasion in specific cancers, we are mining reverse phase protein array (RPPA) data from publicly available human tumor datasets. In this study, we focused on analysis of RPPA data from TCGA in CRC patients, segregated by poor prognosis and good prognosis. We tested three different definitions of poor prognosis: recurrence, survival, and TNM status at diagnosis. We found several promising analytes that were significantly associated with each poor prognosis definition, and recurrence provided the best separation of good vs. poor prognosis. Interestingly, many of the analytes significantly associated with survival are involved in apoptosis. Additionally, we refined the analysis by using a subset of patients (stage I-II), which resulted in even better separation of good vs. poor prognosis. We identified several analytes that are already significantly associated with the invadopodia network (src kinase and PI 3-kinase). We also identified some potential new invadopodia regulators, such as Cox2. This method has potential both to improve CRC survival by identifying patients that need adjuvant therapy as well as identify novel drivers of invadopodia. Citation Format: Christi Lynn French, Alissa Weaver. Identifying analytes associated with poor prognosis in CRC. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4176. doi:10.1158/1538-7445.AM2014-4176

Abstract 2896: Identification of novel tumor associated antigens in colorectal cancer

Abstract The prognosis of colorectal carcinoma (CRC) patients is dependent on the establishment of distant metastasis, which have been shown to arise from a small population of long term tumor initiating cells (LT-TIC). Another major prognostic parameter is the T cell infiltrate in the primary tumor of CRC patients, suggesting that tumor specific T cell responses occur and that the T cell mediated immune surveillance might play an important role in controlling tumor relapse, metastasis and response to treatment. Based on these observations we hypothesize that T cell responses against antigens expressed on TIC might trigger more efficient immune surveillance. So far little is known about the target antigens of the spontaneous T cell responses in CRC patients. In order to identify those antigens in a systematic and unbiased manner, we established a two-dimensional protein separation technique (PF2D). This technique allowed to fractionate lysates from primary and metastatic tumor tissue and to select the fractions which were recognized by the patient's T cell repertoire, as assessed by IFN-γ ELISpot assays. The reactive fractions were further characterized with mass spectrometry (MS) and candidate proteins were verified by use of synthetic peptides in ELISpot. As a result, we have identified 21 novel CRC-associated target antigens of spontaneous T cell responses. We have shown in a cohort of 20 patients that the newly identified target antigens not only triggered responses more frequently than “canonical” tumor antigens that are commonly used for immunotherapy (up to 50% of the tested patients), but the frequency of the T cells specific for the novel tumor associated antigens (TAA) was significantly higher. Furthermore, as shown by gene expression analysis some of the newly identified TAAs were selectively overexpressed on LT-TIC of CRC, and by means of PF2D of LT-TIC enriched spheroid cultures and subsequent MS of the immunogenic fractions, we have demonstrated that they represent target antigens of patients' endogenous T cell responses in all of the tested LT-TIC cultures. In addition, we have identified 30 amino acids long sequences of the these TAA, which elicit CD8+ or CD4+ T cell responses and we are currently working on identification of T cell epitopes and generation of T cell clones specific for these antigens. These would be further used to test the hypothesis that LT-TIC specific T cell clones have the capability to reduce the metastatic potential and tumorigenicity of TIC enriched spheroids in vitro and in vivo. In conclusion we have shown that novel set of antigens expressed in a therapeutically relevant subset of CRC cells, can be highly immunogenic and might serve as better targets for immune monitoring and could be utilized for more efficient T cell based immunotherapy. Citation Format: Slava Stamova, Christoph Schlude, Saskia Rösch, Christel Herold-Mende, Taronish D. Dubash, Claudia R. Ball, Hanno Glimm, Martin A. Schneider, Philipp Beckhove. Identification of novel tumor associated antigens in colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2896. doi:10.1158/1538-7445.AM2014-2896

Tumor deposits in rectal adenocarcinoma after neoadjuvant chemoradiation are associated with poor prognosis

Although tumor deposits have been associated with poor prognosis in colorectal carcinoma, the prevalence and clinical significance of tumor deposits in rectal adenocarcinoma following neoadjuvant chemoradiation are relatively unexplored. The aims of this study are to assess the clinical significance of tumor deposits in rectal adenocarcinoma patients, including those receiving neoadjuvant therapy. Pathology slides and medical records from 205 consecutive patients who underwent resection for rectal adenocarcinoma between 1990 and 2010 at a single tertiary care center were reviewed. Patients with tumor deposits had higher tumor grade (P=0.006) and worse tumor stage (P<0.001) at presentation than patients without tumor deposits. Among 110 patients who underwent neoadjuvant chemoradiation, tumor deposits were associated with higher rates of lymph node involvement (P=0.035) and distant metastases (P=0.006), and decreased survival (P=0.027). These patients had a trend toward lower treatment response scores (P=0.285) and higher local recurrence (P=0.092). Of 52 patients with tumor deposits, those who underwent neoadjuvant chemoradiation had significantly worse pretreatment stage by endoscopic ultrasound (P<0.001) but interestingly had significantly lower rates of lymphovascular invasion on resection (P<0.001) compared with those who had not received neoadjuvant chemoradiation. Despite treatment with neoadjuvant chemoradiation, tumor deposits were present in over one-fifth of rectal adenocarcinoma patients. Overall, the outcome of patients with tumor deposits in treated and untreated patients were similar, however the association of tumor deposits with deeply invasive tumors and less tumor regression when comparing with treated patients without tumor deposits raises the possibility that these tumors could have a more aggressive biology, possibly explaining the association of tumor deposits with higher rates of recurrence and lower survival after neoadjuvant chemoradiation. Overall, tumor deposits appear to be a poor prognostic marker among rectal adenocarcinoma patients following neoadjuvant chemoradiation and may identify a subset of patients who require aggressive adjuvant therapy to prevent recurrence.

Expression and effect of CXCL14 in colorectal carcinoma.

Chemokines are important in the proliferation and metastasis of tumors. CXCL14 is a member of the CXCL chemokine family and exhibits various expression patterns in different types of tumor, even those tumors that occur in the same type of tissue. The expression of CXCL14 and its clinical significance in colorectal carcinoma are unclear. In the present study, the expression levels of CXCL14 in colorectal carcinoma and adjacent normal tissues were detected using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. Kaplan‑Meier survival curves and the Cox regression model were applied to evaluate the clinical significance of the expression levels of CXCL14 in colorectal carcinoma compared with those in normal tissues. To investigate the effects at a cellular level, a replication‑defective lentivirus overexpressing CXCL14 was constructed and transfected into HT29 colorectal carcinoma cells. The effect of CXCL14 on the proliferation of colorectal carcinoma cells and the change in cell cycle distributions were investigated using a cell counting kit‑8 assay and flow cytometry, respectively. Results of the current study indicated that the expression levels of CXCL14 mRNA and protein in colorectal carcinoma were markedly reduced compared with levels in normal tissues (P<0.05). The clinical correlation analysis suggested that downregulation of CXCL14 expression in tumors was associated with lymph metastasis, tumor location, and clinicopathological stage (P<0.05). Kaplan‑Meier survival analysis revealed that downregulation of CXCL14 expression was correlated with a poor prognosis (P<0.01). Overexpression of CXCL14 by lentiviral transfection produced an inhibitory effect on cell proliferation by arresting the cell cycle in the G1 stage. The data of the current study suggest that CXCL14 may be involved in the development and progression of colorectal carcinoma, and may act directly as a potential cancer suppressor gene. The level of CXCL14 expression may be a valuable adjuvant parameter in predicting the prognosis of colorectal carcinoma and may be a potential therapeutic target.

Relationship between miRNA-338-3p expression and progression and prognosis of human colorectal carcinoma

Background miR-338-3p is a recently discovered miRNA and is involved in cell differentiation. However, few data are yet available on the aberrant expression of miR-338-3p in human colorectal carcinoma (CRC). This work aimed to investigate the relationship between miR-338-3p expression pattern and clinicopathological features of human CRC and the possible regulative mechanisms. Methods The 40 CRC, adjacent nontumorous tissues and 2 human CRC-derived cell lines (SW-480 and SW-620) were collected, respectively, and the total RNA and protein were isolated routinely. The miR-338-3p expression pattern was detected by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Northern blotting. Smoothened (SMO, possible target of miR-338-3p) mRNA and corresponding protein expression pattern were detected by semiquantitative RT-PCR and Western blotting. miR-338-3p expression patterns were compared between nontumor mucosa and CRC samples, graded by progression-related factors. Disease outcome was calculated by Kaplan-Meier survival analysis to determine whether miR-338-3p was related to disease-free survival (DFS) and overall survival (OS) of patients. Moreover, SMO 3′-UTR fragment was PCR amplified from genome DNA of human colon and inserted into a luciferase reporter plasmid. The luciferase reporter plasmid construct was then transfected into CRC cells together with pre-miR-338-3p or anti-miR-338-3p and the luciferase activity in the transfected cells was detected. Results The expression of miR-338-3p was significantly downregulated in CRCs than those in the adjacent nontumorous tissues, and the value was negatively related to advanced TNM stage and local invasion (P &lt;0.01). Furthermore, miR-338-3p value was decreased markedly in SW-620 cell line relative to SW-480 (P &lt;0.01). Low expression of miR-338-3p was associated with unfavorable outcome in DFS but not in OS independent of clinical covariates. Moreover, RT-PCR and Western blotting analysis demonstrated that there was no significant difference in SMO mRNA expression between the corresponding CRCs and nontumorous tissues, whereas SMO protein markedly increased in CRCs (P &lt;0.01). A significant increase in luciferase activity was detected in CRC cells, which were cotransfected with the luciferase reporter plasmid construct and anti-miR-338-3p (P &lt;0.01). Conclusions miR-338-3p is expressed differentially in CRC and associated with progression and prognosis of CRC. SMO might be a possible target of miR-338-3p, which made it a potential antitumor candidate for treatment and prevention of CRC. Chin Med J 2014; 127 (10): 1884-1890

C-Myc-mediated repression of miR-15-16 in hypoxia is induced by increased HIF-2α and promotes tumor angiogenesis and metastasis by upregulating FGF2

Previous studies have established the link between aberrant microRNA (miRNA) expression and hypoxia in various neoplasms. However, how these hypoxia-related miRNAs modulate tumor progression is still unclear. Therefore, the patterns of miRNA in colorectal carcinomacell lines inresponse to hypoxia or not were first screened and the hypoxia-induced repression of the miR-15-16 cluster was confirmed. Then, this repression was found to be associated with high tumor stage and poor prognosis in colorectal carcinoma and is shown to promote tumor angiogenesis and metastasis by the loss of restriction of its target gene, fibroblast growth factor-2 (FGF2). Moreover, the general and alterative promoters of the miR-15-16 host (deleted in lymphocytic leukemia 2, DLEU2) were mapped, and three c-Myc/Max binding sites in response to the hypoxia-induced repression of miR-15-16 were further identified. Finally, an enhanced stability of c-Myc/Max heterodimer promoted by increased hypoxia-inducible factor-2α(HIF-2α) was validated, and we also verified that the enhancement contributed to the hypoxia-induced repression of miR-15-16. In brief, the c-Myc-mediated transcriptional repression of miR-15-16 in hypoxia is induced by increased HIF-2α and promotedtumor angiogenesis and hematogenous metastasis by the further loss of post-transcriptional inhibition of FGF2. Our study provides a better understanding of the coping mechanisms in response to tumor hypoxia and may be helpful in developing an effective prognostic marker or treatment target against solid tumors.

Prognostic Role of Nucleophosmin in Colorectal Carcinomas

Recent research suggests that nucleophosmin (NPM) may be a prognostic marker in colorectal carcinomas (CRC). We here tested its use to predict the survival of CRC patients. We investigated NPM expression by immunohistochemistry in histologically normal to malignant colorectal tissues and evaluated its association with clinicopathological variables. Overall and disease-free survival after tumor removal were calculated by the Kaplan-Meier method, and differences in survival curves were analyzed by the log-rank test. The Cox proportional hazards model was used for multivariate analysis of prognostic factors. NPM expression was found significantly upregulated in CRC compared to adjacent colorectal tissue, villous adenoma, tubular adenoma and normal colorectal mucosa (p<0.05 for all). NPM expression was statistically linked to cancer embolus, lymph node metastasis, differentiation grade, and recurrence of CRC. Overall and disease-free survival of NPM-negative CRC patients tended to be better than those for patients with NPM-positive lesions (log-rank statistic, p<0.05 for all). Multivariate analysis indicated NPM expression as an independent prognostic indicator for CRC patients (p<0.05 ). Our results suggest that NPM expression can predict the survival of CRC patients. Prognosis of CRC is determined by not only many known prognostic factors but also by NPM expression.

Prognostic significance of c-erbB-2 and p53 expression in colorectal carcinoma

Objective: Colorectal cancer is the fourth commonest form of cancer occurring worldwide. In order to recognize the prognosis in colorectal carcinoma, a lot of clinic and pathologic parameters such as; tumor size, microscopic type, microscopic grade, depth of invasion, lymph node involvement, invasion of vascular and perineural, tumor stage have been used. In this study, we aimed to compare expression of c-erbB-2, p53 and classical prognostic factors, and to investigate the correlation with prognosis. Methods: In our study, operation materials belonging to 50 colorectal cases were examined retrospectively. Results: Overall, 100 % of colorectal carcinomas had nuclear-staining for p53 protein and 78% of carcinomas cytoplasmic and membranous staining or the c-erbB-2 showing distribution in a heterogeneous fashion. p53 overexpression correlated with (p<0.005) pathologic stage, metastasis of lymph node, invasion of angiolymphatic, differentiation and degree of tumors. c-erbB-2 overexpressions correlated with (p<0,005) histologic differentiation and peritumoral lymphocytic infiltration but not correlated with tumor size, tumor growth pattern, localisation of tumors, pathologic stage, metastasis of lymph node, invasion of angiolymphatic. Conclusion: These results suggest that evaluation of c-erbB-2 and p53 Immunohistochemical expression in colorectal carcinomas may be of value in predicting the clinical course in these patients.

Valor predictivo de la hipoalbuminemia pre-tratamiento sobre el pronóstico del cáncer colorrectal resecado

IntroductionAlbuminemia is part of the antitumoral systemic inflammatory response. We therefore analyzed its possible value in establishing the preoperative prognosis of colorectal carcinoma (CRC). Patients and methodsWe conducted a retrospective, observational study of a series of consecutive patients who underwent CRC resection. Univariate and multivariate analyses of survival curves were performed in patients with and without pre-treatment hypoalbuminemia (<3.5g/dl), both in the overall group of patients and in the subgroup of those with pTNM stage ii tumors. In addition, we compared the 5-year tumor-related mortality in patients with and without hypoalbuminemia. ResultsA total of 207 patients were reviewed (median follow-up: 81 months). In the overall multivariate analysis, survival curves were better in patients with normal albumin levels than in those with hypoalbuminemia (HR=2.82; CI 95%=[1.54-5.19]; P=.001). This better prognostic value of normal albumin levels was also significant in pTNM stage ii tumors: (HR=3.76; CI 95%=[1.40-10.08]; P=.009). The 5-year mortality index was lower in patients with normal albumin levels: overall series=18.8% vs 42.9% (OR=3.24; CI 95%=[1.48-7.12]; p=0.001); pTNM stage ii=13.3% vs 44.4% (OR=5.2; CI 95%=[1.36-20.34]; P=0.004). ConclusionsPre-treatment hypoalbuminemia (<3.5g/dl) was independently related to shorter survival after tumor resection, both in the overall series of patients and in pTNM stage ii CRC. If these results are confirmed, hypoalbuminemia would be a simple and significant marker of poor prognosis, available at the initial diagnosis.

Prognostic criteria in colorectal carcinoma constructed by the combination of tumor-related and host-related factors

BackgroundThe significance of prognostic criteria based on a combination of tumor-related and host-related factors for patients with colorectal carcinoma has not been appreciated fully. MethodsCorrelation of tumor-related and host-related score (TRHRS), which are constructed by the combination of serum elevation of C-reactive protein and pathologic lymph node metastasis (scores ranging 0 to 2), with clinicopathologic features including prognosis was studied in 271 patients with colorectal carcinoma who had been treated with curative resection. ResultsSignificant difference regarding survival was observed both between TRHRS 0 and 1 (P = .028) and between TRHRS 1 and 2 (P < .0001). Multivariate analysis showed that histologic types (P = .040) and TRHRS (P < .0001) were independent prognostic indicators. ConclusionCriteria for the prediction of prognosis in colorectal carcinoma treated with curative resection based on both tumor-related and host-related factors could provide a strict stratification.

Diagnostic and prognostic significance of different mucin expression, preoperative CEA, and CA-125 in colorectal carcinoma: A clinicopathological study.

Background:Colorectal carcinoma (CRC) is the fourth most commonly diagnosed malignant disease worldwide, with over 1 million new cases and approximately 5,00,000 deaths each year.Aims and Objectives:This prospective observational study was done to study the clinicopathological characteristics of CRC including mucin stains and correlate the preoperative serum carcinoembryonic antigen (CEA) and cancer antigen (CA)-125 levels with the prognosis.Materials and Methods:A total of 90 CRCs were included from December 2010 to June 2013. Detailed history and relevant clinical/radiological findings were noted in all clinically and/or radiologically suspected cases of CRC. Preoperative blood samples were collected for serum CEA and CA-125 level estimation. The mucin expression was evaluated with special stains.Results:The combined Alcian blue-periodic acid Schiff (PAS) staining was positive for both stains in 68.88% cases indicating that both neutral and acidic mucins are increased in CRC. High preoperative serum CEA levels were seen in 82.22% cases, whereas preoperative serum CA-125 levels showed an increase in 20% cases. Higher levels of these tumor markers corresponded with higher TNM stage.Conclusions:Mucin evaluation in CRCs remains one of the valuable methods as mucinous variants correlate with worse prognosis. Preoperative serum CEA level assessment is an indispensible adjunct to the diagnosis and prognosis of CRC. However, preoperative serum CA-125 level measurement is not an efficient tool for prognostication in CRC and should not be recommended for routine use.

Das Kolitis-assoziierte kolorektale Karzinom: Epidemiologie, Pathogenese und Früherkennung

Colitis-associated colorectal carcinoma (CRC) accounts for about 5% of all CRC and the risk for CRC in inflammatory bowel disease (IBD) patients - according to older meta-analyses - is slightly increased when compared to normal population. Effective anti-inflammatory therapy seems to decrease this risk. Main risk factors for colitis-associated CRC are pancolitis, duration of colitis and presence of primary sclerosing cholangitis. In contrast to sporadic CRC, a characteristic adenoma-carcinoma sequence in the pathogenesis of colitis-associated CRC cannot be found. Nevertheless, numerous cell and gene defects occur. Reactive oxygen species also seem to play a pivotal role in the pathogenesis of colitis-associated CRC. Particularly patients with chronically active pancolitis should undergo regular surveillance colonoscopy, since prognosis of colitis-associated CRC is poor.

MicroRNA-191 correlates with poor prognosis of colorectal carcinoma and plays multiple roles by targeting tissue inhibitor of metalloprotease 3

MicroRNA-191 (miR-191) is reported to be overexpressed in colorectal carcinoma (CRC), but the role of miR-191 in CRC progress remained unclear. This study demonstrated that High miR-191 expression was associated with clinical stage, lymph node metastasis, liver metastasis and depth of tumor invasion. Kaplan-Meier analysis indicated that patients with high miR-191 expression had a poor overall survival. Moreover, multivariate analysis showed that miR-191 was an independent prognostic factor in patients with CRC. Furthermore, we found that tissue inhibitor of metalloprotease 3 (TIMP3) was a direct target of miR-191 in colorectal cancer SW620 cells. TIMP3 downregulation mediated by miR-191 activated matrix metalloproteinases (MMPs) and thus promoted invasiveness of cancer cells. Anti-miR-191 could attenuate the invasiveness, suppress proliferation and induce apoptosis by restoring TIMP3 expression. Our results suggested that miR-191 might be a potential diagnostic and therapeutic target in patients with colorectal cancer.