Prognostic Factor In Colorectal Carcinoma Research Articles

Tumor Budding in Colorectal Carcinoma: Translating a Morphologic Score Into Clinically Meaningful Results.

- Tumor budding has received increasing recognition as an important independent prognostic factor in colorectal carcinoma. Prominent tumor budding in adenocarcinoma arising in a polyp has been shown to be a risk factor for lymph node involvement. The variability in methods used for evaluating tumor budding in different studies and lack of standardized guidelines have impeded routine inclusion of tumor budding in pathology reports. This changed last year with consensus guidelines based on the International Tumor Budding Consensus Conference (ITBCC). These guidelines have been included in the recent College of American Pathologists (CAPs) Colorectal Cancer Protocol. The consensus methodology will allow uniform reporting of this finding, but challenges in interpretation in the setting of intense inflammation, fibrosis, or gland fragmentation need to be addressed in future guidelines. - To provide a brief overview of the known clinical significance of tumor budding in colorectal carcinoma and discuss the practical aspects of its implementation on a routine basis. - English-language pathology literature. - Tumor budding has been shown to be an independent prognostic marker in colorectal carcinomas and the routine reporting of tumor buds is now advocated by using the approach outlined by the ITBCC guidelines. Tumor budding is included in the CAP protocol as a recommended element. Presence of prominent tumor budding in an adenocarcinoma in a polyp may have implications for management, such as additional resection, while it serves as a prognostic factor in other settings.

Expression of Aldehyde Dehydrogenase 1A1 (ALDH1A1) as a Prognostic Biomarker in Colorectal Cancer Using Immunohistochemistry.

BackgroundThe expression of aldehyde dehydrogenase 1A1 (ALDH1A1) is increased in several human tumors, including colorectal carcinoma (CRC). The aim of this study was to compare the expression ALDH1A1 in CRC tumor tissue compared with non-tumor adjacent tissue (NAT), using immunohistochemistry (IHC), and to determine whether the expression of the ALDH1A1 protein was associated with prognostic factors in CRC.Material/MethodsFormalin-fixed paraffin-embedded (FFPE) tissue from 424 patients diagnosed with CRC, and 196 matched NATs were used to prepare tissue microarrays (TMAs). IHC was performed using an immunoperoxidase method with a primary polyclonal rabbit anti-ALDH1A1 antibody. The IHC scores by light microscopy were the staining intensity (scored from 0–3) multiplied by the percentage area of positive immunostaining within the visual field (scored from 0–4). Associations between tumor expression levels of ALDH1A1 and patient clinicopathological characteristics, including tumor grade, size, and TNM stage at surgery were analyzed.ResultsALDH1A1 protein expression was significantly increased in CRC tissues compared with matched NATs. In patients with CRC, increased expression of the ALDH1A1 protein was significantly associated with the presence of lymph node metastasis: 64.28% in N0 cases; 75.49% in N1 cases; and 82.14% in N2 cases, (P=0.002). Univariate and multivariate analysis showed that ALDH1A1 expression was an independent prognostic marker for CRC (P<0.001).ConclusionsUsing IHC, the expression of the ALDH1A1 protein in CRC tissues was significantly associated with the presence of lymph node metastases and might be a potential prognostic marker in patients with CRC.

Interobserver variability in the H&E-based assessment of tumor budding in pT3/4 colon cancer: does it affect the prognostic relevance?

Tumor budding is a mostly accepted adverse prognostic factor in colorectal carcinoma. It is on the cusp of a widespread use after agreement was reached recently on uniform assessment criteria. We investigated whether the interobserver variability has a direct influence on the prognostic relevance in pT3/4 colon cancer in the background of different levels of experience of the investigators. In total, six investigators with different levels of experience evaluated tumor budding on H&E slides in 244 cases with primary diagnosed (2002-2011) colon carcinoma (pT3/4, N+/-, M0). High-grade tumor budding/budding grade 3 (defined as majority assessment among the investigators) was significantly associated with an adverse outcome (overall survival p = 0.03, cancer-specific survival p = 0.08) and the occurrence of distant metastasis (p = 0.009). However, a detailed analysis of the rating results of the individual investigators revealed that only ratings of one investigator (advanced resident) were associated with an adverse outcome (p = 0.01 cancer-specific survival, overall survival p = 0.09, distant metastasis p = 0.002). The results of another investigator (consultant) were significantly associated with distant metastasis (p = 0.007). The kappa values among the investigators have a range between 0.077 and 0.357 (median 0.166). Total agreement of all investigators existed in 109 cases (44.7%). Our results demonstrate that the evaluation of tumor budding on H&E slides in pT3/4 colon cancer goes along with a considerable interobserver variability among investigators of different levels of experience. Furthermore, our results reveal that these findings directly influence the prognostic value.

HtrA3 stromal expression is correlated with tumor budding in stage II colorectal cancer

Tumor budding is a well-established adverse prognostic factor in colorectal carcinoma (CRC). It may represent a form of epithelial-to-mesenchymal transition (EMT), although the underlying mechanisms remain unclear. High-temperature requirement A3 (HtrA3) is an inhibitor of the bone morphogenetic protein pathway, the suppression of which has been linked to EMT. Since HtrA3 is highly expressed in the desmoplastic stroma at the CRC invasive front, we sought to evaluate the relationship between tumor budding and HtrA3 expression in 172 stage II CRC resection specimens. All tumors were evaluated for tumor budding, with the highest budding slide selected for pan-keratin (CK) and HtrA3 immunohistochemistry. Representative areas of tumor core and invasive front, including budding and non-budding areas, were marked on CK stained slides, and then evaluated on HtrA3 stained slides. HtrA3 expression in tumor cells (tHtrA3) and peritumoral stroma (sHtrA3) was assessed for staining percentage and intensity (the product yielding a final score). Tumors with high-grade tumor budding (HGTB) showed increased expression of sHtrA3 in budding areas compared to non-budding areas at the invasive front (P<0.001). In addition, sHtrA3 expression at the invasive front was significantly higher in HGTB tumors compared to minimally budding tumors (P<0.05). tHtrA3 expression at the invasive front was significantly associated with high histological grade (P<0.05). Higher sHtrA3 expression in the tumor core (but not invasive front) was significantly associated with decreased 5-year overall survival on univariate analysis (P<0.05), but not multivariate analysis. HtrA3 expression in the peritumoral stroma of patients with stage II CRC is associated with HGTB and may be a novel marker of poor outcome.

Abstract 5007: Role of the interferon-gamma response pathway in immune escape of colorectal carcinoma

Abstract The presence of an interferon-dominated Th1 immune response in colorectal carcinoma (CRC) has been associated with improved clinical outcome. We have previously identified the guanylate-binding protein 1 (GBP-1), one of the major IFN-γ-induced proteins, as a marker for the Th1 immune response and an independent positive prognostic factor in CRC. We also found that GBP-1 is a necessary mediator of the anti-tumorigenic effects of IFNγ. Interestingly, the expression of GBP-1 in CRC was observed more frequently in the desmoplastic stroma than in the directly adjacent tumor cells, suggesting that CRC tumor cells might become resistant to IFN-γ in the course of tumorigenesis. Indeed, we found that several colorectal carcinoma cell lines failed to express GBP-1 or other interferon-stimulated genes after treatment with IFN-γ, and were resistant to IFN-γ-induced apoptosis or proliferation inhibition. In these cell lines, the loss of IFN-γresponsiveness correlated either with the down-regulation of the IFN-γ receptor alpha chain (IFNγRα) or with the presence of a mis-glycosylated form of IFNγRα, which displayed an aberrant intracellular localization. We further validated these findings at the clinical level by showing that the expression of IFNγRα is decreased in CRC compared to normal tissue. In addition, the down-regulation of IFNγRα expression in CRC correlated with a reduced cancer-related survival together with a higher rate of distant metastasis. In addition, in-vivo colon tumorigenesis models using conditional knock-out mice revealed that the absence of IFNγRα expression by intestinal epithelial cells fosters tumor growth. Altogether, our data suggest that the loss of IFN-γ responsiveness is a common event in CRC and protects tumor cells against the anti-tumorigenic effects of IFN-γ. Citation Format: Nathalie Britzen-Laurent, Julia Straube, Philipp Tripal, Maximilian Waldner, Christoph Becker, Susanne Merkel, Roland S. Croner, Michael Sturzl. Role of the interferon-gamma response pathway in immune escape of colorectal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5007. doi:10.1158/1538-7445.AM2017-5007

Baseline serum albumin and other common clinical markers are prognostic factors in colorectal carcinoma: A retrospective cohort study.

The aim of the present study was to define the prognostic role of baseline serum albumin (BSA) in colorectal cancer (CRC) across tumor-node-metastasis (TNM) stages and other well defined prognostic factors. Many prognostic models in medicine employ BSA to define or refine treatments in very specific settings; in CRC, BSA has been found to be a prognostic factor as well. A retrospective cohort study of consecutive patients with CRC demonstrated by biopsy, who attended a cancer center during a 7-year period. Multivariate analysis was utilized to define prognostic factors associated with overall survival (OS) employing the Cox model. In this retrospective cohort study, 1465 patients were included; 46.6% were females and 53.4% males (mean age, 59.1 years). Mean BSA was inversely correlated with TNM stages. By multivariate analysis, it was an independent explanatory variable. TNM stages, "R" classification, age, lymphocyte count, neutrophil/platelet ratio, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, postoperative morbidity, and BSA were independently associated with OS. Morbidities, surgery type, chemotherapy, and radiotherapy were considered confounders after adjusting by TNM stages. BSA is a significant and independent prognostic factor in patients with CRC, and its effect is maintained across TNM strata and other well known clinical prognostic factors. It can be easily used in prognostic models and should be employed to stratify prognosis in therapeutic randomized clinical trials.

P16 protein is upregulated in a stepwise fashion in colorectal adenoma and colorectal carcinoma.

Background/Aims:p16 is tumor suppressor gene acting as a cell cycle regulator. The present study was conducted to compare p16 expression in normal, dysplastic, and malignant colonic mucosae, and to explore its relation to clinicopathological variables and follow-up data in colorectal carcinoma (CRC).Patients and Methods:Tissue microarrays were performed from 25 normal colonic mucosae, 41 colonic adenomas, and 191 CRC, with corresponding 50 nodal metastases. Immunohistochemistry was performed using anti-p16 antibody, sections were scored, and statistical analysis was performed. K-ras mutation detection was also performed.Results:Immunoexpression of p16 was significantly higher in CRC than in adenomas (P = 0.033) and normal colonic mucosa (P = 0.005). There was no statistically significant difference between p16 expression in CRC and nodal metastasis. There was no significant association between p16 immunoexpression in CRC and all clinicopathological data and survival probability. K-ras mutations were detected in 34% of CRC. However, there was no correlation between K-ras status and p16 expression (P = 0.325).Conclusion:Absence of p16 expression is correlated to a benign course of CRC adenomas. p16 has a key role in CRC progression and can be used as a marker for colorectal adenoma. On the other hand, it has no role as a predictive and/or prognostic factor in CRC. Further extended studies are required to explore the role of p16 as indicator of premalignant lesions in the colon and to test its relation with CRC histological grade, as well as to test its value as a new therapeutic target.

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.

Relation of glypican-3 and E-cadherin expressions to clinicopathological features and prognosis of mucinous and non-mucinous colorectal adenocarcinoma.

Glypican-3 (GPC3) is a member of the membrane-bound heparin sulfate proteoglycans. E-cadherin is an adhesive receptor that is believed to act as a tumor suppressor gene. Many studies had investigated E-cadherin expressions in colorectal carcinoma (CRC) while only one study had investigated GPC3 expression in CRC. This study aims to investigate expression of GCP3 and E-cadherin in colorectal mucinous carcinoma (MA) and non-mucinous adenocarcinoma (NMA) using manual tissue microarray technique. Tumor tissue specimens are collected from 75 cases of MC and 75 cases of NMA who underwent radical surgery from Jan 2007 to Jan 2012 at the Gastroenterology Centre, Mansoura University, Egypt. Their clinicopathological parameters and survival data were revised and analyzed using established statistical methodologies. High-density manual tissue microarrays were constructed using modified mechanical pencil tip technique and immunohistochemistry for GPC3 and E-cadherin was done. NMA showed higher expression of GPC3 than MA with no statistically significant relation. NMA showed a significantly higher E-cadherin expression than MA. GPC3 and E-cadherin positivity rates were significantly interrelated in NMA, but not in MA, group. In NMA group, there was no significant relation between either GPC3 or E-cadherin expression and the clinicopathological features. In a univariate analysis, neither GPC3 nor E-cadherin expression showed a significant impact on disease-free survival (DFS) or overall survival (OS). GPC3 and E-cadherin expressions are not independent prognostic factors in CRC. However, expressions of both are significantly interrelated in NMA patients, suggesting an excellent interplay between both, in contrast to MA. Further molecular studies are needed to further explore the relationship between GCP3 and E-cadherin in colorectal carcinogenesis.

Immunohistochemical expression of Twist in colorectal carcinoma

Objectives The aim of this study was to explore the relationship between immunohistochemical expression of Twist and the relevant clinicopathological features of colorectal carcinoma (CRC) in Egyptian patients. Background In Egypt, there is an increasing incidence of CRC, especially among patients of 40 years of age or less. Worldwide, many efforts have been made to find biomarkers to predict the behavior of CRC. Epithelial-mesenchymal transition is one of the central mechanisms that induces invasion and metastasis of tumors. Twist has been shown to induce epithelial-mesenchymal transition and play a critical role in cancer metastasis. In addition, Twist proteins display oncogenic properties by preventing senescence and apoptosis. Materials and methods Using the standard immunohistochemical technique, we assessed Twist expression in 67 colorectal specimens, including 10 specimens from normal colonic mucosa, eight colonic adenoma, and 49 CRC cases, and correlated our results with the available clinicopathological parameters. Results Negative Twist cytoplasmic immunoreactivity was detected in all the normal colonic mucosa specimens, whereas 75% of adenomas and 85.7% of CRC showed positive Twist cytoplasmic expression. Negative Twist nuclear immunoreactivity was detected in all the normal colonic mucosa and adenoma specimens, whereas 44.9% of CRC showed positive nuclear Twist expression. Nucleocytoplasmic Twist expression was significantly associated with high-grade tumors, mucinous adenocarcinoma, and advanced Dukes' stage, and showed a high tendency to be associated with vascular invasion. Conclusion The negativity of Twist in normal colonic mucosa confirm Twist as an embryonic transcription factor that remains largely undetectable in healthy adult tissues and involved in oncogenesis and malignant transformation in CRC. Being negative in adenoma and expressed only in CRC, Twist nuclear translocation may be a late event in carcinogenesis. Nucleocytoplasmic Twist expression is associated with poor prognostic factors in CRC.

Loss of Anterior Gradient-2 expression is an independent prognostic factor in colorectal carcinomas

AimsThe human Anterior Gradient-2 (AGR2) protein is strongly expressed in various human cancers, and it has been described to promote aggressive tumour features in some entities. So far, a comprehensive analysis of AGR2 expression in colorectal carcinomas has not been described. MethodsNormal intestinal cells and colorectal carcinoma cell lines were analysed for AGR2 expression. AGR2 protein expression was immunohistochemically analysed in 28 normal tissue samples and 1068 tissue samples of clinically well characterised colorectal carcinomas. For statistical analysis, chi square test, spearman rank correlations, Kaplan–Meier estimates (Log rank test) and Cox regression were applied to test for diagnostic or prognostic associations. ResultsIn the normal intestinal cell line and in normal colon mucosa AGR2 was found in all cases (n=28). In contrast, loss of AGR2 was found in all six analysed colorectal cancer cell lines and in 833/1068 (78%) of the colorectal carcinoma tissue samples analysed, and it was significantly associated with a higher tumour grade and tumour localisation in the left-sided colon. In addition to the conventional prognostic tumour parameters pT category, nodal status, metastasis and histological tumour grade the loss of AGR2 expression was significantly associated with reduced overall survival times in univariate and multivariate analyses, thus suggesting AGR2 as an independent prognostic factor in primary colorectal carcinoma. ConclusionsAGR2 is frequently lost in colorectal carcinomas and might be a novel independent prognostic factor for overall patient survival.

Prognostic and Diagnostic Significance of Tumor Budding Associated with β-Catenin Expression in Submucosal Invasive Colorectal Carcinoma

Endoscopic resection has become a major curative treatment for early colorectal carcinoma without lymph node metastasis. However, lymph node metastasis, a poor prognostic factor in colorectal carcinoma, occurs in about 10% of the patients with submucosal invasive colorectal carcinoma. Therefore, it is important to identify a high-risk factor for lymph node metastasis in submucosal invasive colorectal carcinoma. This study was designed to identify the relationship between tumor budding with β-catenin expression and lymph node metastasis in submucosal invasive colorectal carcinoma. We investigated the immunohistochemistry of tumor budding in the 142 patients who underwent surgical resection for submucosal invasive colorectal carcinomas between 1984 and 1999 and the expression pattern of β-catenin in budding tumor cells. Accordingly, all the patients were followed up for at least 10 years or until death. Among the 142 patients, lymph node metastasis was detected in 14 patients (9.9%). Univariate analysis showed that tumor budding with ≥ 5 tumor cells or cell clusters with expression of β-catenin in the nucleus was significantly associated with lymph node metastasis (P = 0.005). In contrast, tumor budding detected by hematoxylin and eosin staining was not associated with lymph node metastasis. Multivariate logistic regression analysis showed that tumor budding with ≥ 5 tumor cells or cell clusters with expression of β-catenin in the nucleus was a significant risk factor for lymph node metastasis (odds ratio, 7.124; 95% confidence interval, 1.407-36.062). Thus, tumor budding associated with β-catenin expression is a risk factor for lymph node metastasis in submucosal invasive colorectal carcinoma.

The relationship between the stromal mast cell number, microvessel density, c-erbb-2 staining and survival and prognostic factors in colorectal carcinoma

Colorectal adenocarcinomas take second place among the causes of death from carcinoma, and account for 98% of colorectal carcinomas. There is a need to determine new prognostic factors because of high frequency and significance. 204 colorectal carcinomas diagnosed between 01.01.2005 - 31.12.2008 at Uludağ University Medical Faculty Pathology Department were studied for Factor VIII and c-erbB-2 immunohistochemically and with toluidine blue stain histochemically. Association of mast cell number, microvessel density, and c-erbB-2 staining pattern with survival and known prognostic factors was evaluated. Follow-up period was 4-60 months. A total of 111 cases were alive, and 65 had died. The mean number of mast cells was 8.00 (1-21) and the mean density of microvessels was 10.00 (2-21). Five-year survival rate of the mast cell group was 48.3% for values under 10 and 57.9% for values of 10 and higher. Five-year survival rate was 58.2% in the group with a microvessel density of 10 and above and 45.9% for values under 10. Five-year survival rate was 53.9% for the group with c-erbB-2 cytoplasmic staining and 48.2% for the group with membranous staining. The grade increased with the number of mast cells, while survival decreased with an increase in the number of mast cells. The ratio of c-erbB-2 staining increased as the grade and stage increased. There was an association between mast cell number and microvessel density. We found no relationship between prognosis and c-erbB-2, mast cell number, and microvessel density.

Downregulation of Mus81 as a novel prognostic biomarker for patients with colorectal carcinoma

The Mus81 gene encodes a critical endonuclease involved in DNA repair and tumor suppression. Our previous study has shown reduced expression of Mus81 in hepatocellular carcinoma and its association with the metastatic potential and prognosis of hepatocellular carcinoma. However, the role of Mus81 in colorectal carcinoma is currently unknown. We therefore carried out the present study to explore the correlation between Mus81 expression and the progression of colorectal carcinoma. Mus81 expression in 92 cases of colorectal carcinoma and matched normal tissues was determined by quantitative real-time polymerase chain reaction. Our results showed that Mus81 expression in colorectal carcinoma tissues was significantly reduced compared with the corresponding normal tissues (P < 0.001) and the downregulation of Mus81 (decreased by more than 50%) was found in 60.9% (56/92) of colorectal carcinoma. Moreover, Mus81 downregulation correlated significantly to hepatic metastasis (P = 0.019) and a high TNM stage (P = 0.025) of colorectal carcinoma. In addition, the decrease of Mus81 was also detected in 10 cases of hepatic metastasis tissues compared with the corresponding primary colorectal carcinoma tissues (P = 0.016). More importantly, colorectal carcinoma patients with apparent Mus81 downregulation have shown significantly poorer overall survival than those with little Mus81 downregulation (P = 0.0374). Also, multivariable Cox regression analysis identified Mus81 downregulation as an independent prognostic factor for colorectal carcinoma (hazard ratio, 1.678; P = 0.040). In conclusion, the reduced expression of Mus81 is closely related to hepatic metastasis and poor prognosis of colorectal carcinoma, indicating Mus81 as a novel prognostic marker for colorectal carcinoma.

Tumor infiltration by FcγRIII (CD16)+ myeloid cells is associated with improved survival in patients with colorectal carcinoma

The prognostic significance of macrophage and natural killer (NK) cell infiltration in colorectal carcinoma (CRC) microenvironment is unclear. We investigated the CRC innate inflammatory infiltrate in over 1,600 CRC using two independent tissue microarrays and immunohistochemistry. Survival time was assessed using the Kaplan-Meier method and Cox proportional hazards regression analysis in a multivariable setting. Spearman's rank correlation tested the association between macrophage and lymphocyte infiltration. The Basel study included over 1,400 CRCs. The level of CD16+ cell infiltration correlated with that of CD3+ and CD8+ lymphocytes but not with NK cell infiltration. Patients with high CD16+ cell infiltration (score 2) survived longer than patients with low (score 1) infiltration (p = 0.008), while no survival difference between patients with score 1 or 2 for CD56+ (p = 0.264) or CD57+ cell (p = 0.583) infiltration was detected. CD16+ infiltrate was associated with improved survival even after adjusting for known prognostic factors including pT, pN, grade, vascular invasion, tumor growth and age [(p = 0.001: HR (95% CI) = 0.71 (0.6-0.9)]. These effects were independent from CD8+ lymphocyte infiltration [(p = 0.036: HR (95% CI) = 0.81 (0.7-0.9)] and presence of metastases [(p = 0.002: HR (95% CI) = 0.43 (0.3-0.7)]. Phenotypic studies identified CD16+ as CD45+CD33+CD11b+CD11c+ but CD64- HLA-DR-myeloid cells. Beneficial effects of CD16+ cell infiltration were independently validated by a study carried out at the University of Athens confirming that patients with CD16 score 2 survived longer than patients with score 1 CRCs (p = 0.011). Thus, CD16+ cell infiltration represents a novel favorable prognostic factor in CRC.

Negative prognostic factors in colorectal carcinoma: An analysis of 448 patients

Colorectal carcinoma (CRC) is the most frequent malignancy of the gastrointestinal tract. Prognostic researches are carried out for choosing the optimum therapy, evaluating therapy results and comparing multicentre results for better qualification in the therapy of the disease. In this study, 448 patients, whose surgery and follow-up was performed by the same correspondent surgeon between the years 1995 and 2003, were retrospectively analyzed. Age, presence of comorbidity, weight loss, emergency admission, high serum CEA and CA 19-9 levels, neighboring organ invasion, operation type, major morbidity, tumor size and type, lymph node metastases, venous and perineural invasion, Dukes' classification and local recurrence and distant metastasis during follow-up are found to be significant negative factors affecting prognosis of the CRC patient. Therapy results of the CRC are evaluated by survival times regardless of the therapy method selected for each individual. In our study we tried to find out negative prognostic factors by researching possible factors affecting disease free survival time for CRC. Since our understanding of factors that have an impact on prognosis increases, we are hoping to improve survival.

S1975 Is Bowel Obstruction at Presentation an Independent Adverse Prognostic Factor in Colorectal Carcinoma?

S1975 Is Bowel Obstruction at Presentation an Independent Adverse Prognostic Factor in Colorectal Carcinoma?

Abstract B33: Prognostic role of Wnt/beta-catenin pathway in colorectal carcinoma

Abstract Introduction: Beta-catenin is a member of a cadherin-catenin complex mediating cell adhesion. It is also a key protein of Wnt/Beta-catenin pathway responsible for cell cycle and proliferation. This is important for initiation and progression of colorectal cancer. The aim of this study was to determine expression and localization of E-cadherin, Beta-catenin and Wnt-1 proteins in colorectal tumors. Description: Forty-four unrelated patients with advanced colorectal carcinoma (CRC) were enrolled consecutively from CRC patients attending palliative care. Expression of Beta-catenin, E-cadherin and Wnt-1 was determined by immunohistochemistry on formalin-fixed, paraffin-embedded primary colorectal tissue. The expression was scored by two independent observers who had no knowledge of the clinical data. Correlation was measured with Spearman test, overall survival were analyzed with Kaplan-Meier method. Log-rank test was used for univariate analysis, while Cox regression model for multivariate analysis. A value of p &amp;lt; 0,05 was considered significant. Results: Decreased expression of membrane E-cadherin and Beta-catenin was observed in 34% and 27% of patients, respectively. Abnormal cytoplasmic E-cadherin was detected in 32% of cases and abnormal cytoplasmic and nuclear Beta-catenin was detected in 50% and 25% of patients, respectively. 60% of patients had decreased cytoplasmic Wnt-1 expression. Correlation was seen between cytoplasmic E-cadherin and cytoplasmic Beta-catenin (R 0,35; p=0,019). Nuclear localization of Betacatenin was correlated with localization of primary tumor (the highest expression in rectum) (R 0,48; p=0,001) and tumor size (R 0,32; p=0,035). Lower Wnt-1 expression was correlated with higher nodal stage (R -0,31; p=0,047). Nuclear Beta-catenin was an adverse prognostic factor in univariate analysis (log-rank test p=0,034) which was confirmed in multivariate analysis (HR 4,27 95% CI 1,70–10,72; p=0,002). Higher CEA serum level before treatment (HR 4,30 95% CI 1,35–13,66; p=0,013) and female sex (HR 2,75 95% CI 1,24–6,10; p=0,013) were also independent prognostic factors. Conclusions: This finding supports that Beta-catenin is an independent prognostic factor for colorectal carcinoma. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B33.

Number of Lymph Nodes Examined and Associated Clinicopathologic Factors in Colorectal Carcinoma

Nodal metastasis is one of the most important prognostic factors in colorectal carcinoma. The number of lymph nodes recovered and examined in resection specimens has been recently shown to be critical for proper staging and is associated with survival. To assess the clinicopathologic factors that may be associated with the number of lymph nodes harvested from surgical resections. Clinicopathologic factors of 434 consecutive cases of colorectal cancers treated by surgical resection from a single tertiary medical center were retrospectively reviewed and correlated with number of lymph nodes recovered. Our data show that patient age, tumor location, and length of resected bowel segment were associated with number of lymph nodes harvested in surgical resections of colorectal cancer. The average number of lymph nodes was 18.2 and 17.8 for patients younger than 50 years and aged 50 through 60 years, respectively, whereas it was 14.4, 15.1, and 14.9 for patients aged 61 through 70 years, 71 through 80 years, and 80 years and older, respectively. More lymph nodes were present in resection specimens of cecum/ascending colon and descending colon cancers than in those of transverse colon, sigmoid colon, and rectal cancers. There was a linear increase in number of lymph nodes examined with increasing length of bowel resection specimens. In multivariate regression analysis, the factors that remained independent predictors of removal of 12 or more lymph nodes from resection specimens were tumor location and length of resected bowel segment. The number of lymph nodes obtained in resection specimens for colorectal cancer was significantly associated with the length of resected segments of bowel, patient age, and location of the tumor.

Number of lymph nodes examined and associated clinicopathologic factors in colorectal carcinoma.

Abstract Context.—Nodal metastasis is one of the most important prognostic factors in colorectal carcinoma. The number of lymph nodes recovered and examined in resection specimens has been recently shown to be critical for proper staging and is associated with survival. Objective.—To assess the clinicopathologic factors that may be associated with the number of lymph nodes harvested from surgical resections. Design.—Clinicopathologic factors of 434 consecutive cases of colorectal cancers treated by surgical resection from a single tertiary medical center were retrospectively reviewed and correlated with number of lymph nodes recovered. Results.—Our data show that patient age, tumor location, and length of resected bowel segment were associated with number of lymph nodes harvested in surgical resections of colorectal cancer. The average number of lymph nodes was 18.2 and 17.8 for patients younger than 50 years and aged 50 through 60 years, respectively, whereas it was 14.4, 15.1, and 14.9 for patients aged...