scholarly journals Association between c-Met and lymphangiogenic factors in patients with colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22199-e22199
Author(s):  
Kyoungha Kim ◽  
Hanjo Kim ◽  
Min Young Lee ◽  
Tae Sung Ahn ◽  
Jina Yun ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Tumor Cells ◽  
Cancer Metastasis ◽  
Prognostic Significance ◽  
Indirect Evidence ◽  
High Expression ◽  
Lymph Node Status ◽  
Vegf Receptor

e22199 Background: Lymphangiogenesis plays an important role in cancer metastasis. Although animal models show a strong relationship between lymphangiogenesis and lymph node metastasis and survival, the clinical significance of lymphangiogenesis in colorectal cancer (CRC) remains uncertain. The goal of this study was to evaluate the association between c-Met and lymphangiogenic factors and to elucidate their prognostic significance for patients with CRC. Methods: A total of 379 tissue samples were obtained from surgically resected specimens from patients with CRC in Soonchunhyang University Cheonan Hospital between January 2002 and December 2010. The expressions of c-Met, vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, and podoplanin were examined by immunohistochemistry. The expression of each marker and clinical factors were analyzed. Results: Three hundred and one of 379 (79.4%) tissues had c-Met expression. High expression of c-Met in tumor cells was significantly associated with high expression of VEGF-C (P < .001) and VEGFR-3 (P = .001). But, there was no statistically significant association with podoplanin (P = .587) and VEGF-D (P = .096). Of the 103 evaluable patients, expression of c-Met in tumor cells was significantly associated with advanced clinical stage (P = .020), positive lymph node status (P = .038), and high expression of VEGF-C (P = .020). But, there was no statistically significant association with podoplanin (P = .518), VEGFR-3 (P = .085), VEGF-D (P = .203), and overall survival (P = .360). Conclusions: Our results provide indirect evidence for an association and possible regulatory link of c-Met with the lymphangiogenic factors. But, c-Met expression in patients with CRC are not prognostic indicator for overall survival in this retrospective study.

The Clinical and Prognostic Significance of Protein Arginine Deiminases 2 and 4 in Colorectal Cancer

Pathobiology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Mohamed Gijon ◽  
Rachael L. Metheringham ◽  
Michael S. Toss ◽  
Samantha J. Paston ◽  
Lindy G. Durrant
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Survival Time ◽  
Patient Survival ◽  
Prognostic Significance ◽  
High Expression ◽  
Related Protein ◽  
Post Translational Modification

<b><i>Introduction:</i></b> Protein arginine deiminases (PADIs) are a family of enzymes that catalyse the post-translational modification of proteins. Association between PADI expression and clinicopathology, protein expression, and outcome was determined. <b><i>Methods:</i></b> PADI2 and PADI4 expression was assessed immunohistochemically in a cohort of colorectal cancer (CRC) patients. <b><i>Results:</i></b> CRC tissues expressed variable levels of PADI2 which was mainly localised in the cytoplasm and correlated with patient survival (<i>p</i> = 0.005); high expression increased survival time from 43.5 to 67.6 months. Expression of cytoplasmic PADI2 correlated with the expression of nuclear β catenin, PADI4, and alpha-enolase. In contrast, expression of nuclear PADI2 correlated with a decrease in survival (<i>p</i> = 0.010), with high expression decreasing survival from 76.4 to 42.9 months. CRC tissues expressed variable levels of PADI4 in both the nucleus and cytoplasm. Expression of cytoplasmic PADI4 correlated with survival (<i>p</i> = 0.001) with high expression increasing survival time from 48.1 to 71.8 months. Expression of cytoplasmic PADI4 correlated with expression of nuclear β catenin, alpha-enolase (<i>p</i> ≤ 0.0001, <i>p</i> = 0.002), and the apoptotic related protein, Bcl-2. Expression of nuclear PADI4 also correlated with survival (<i>p</i> = 0.011), with high expression of nuclear PADI4 increasing survival time from 55.4 to 74 months. Expression of nuclear PADI4 correlated with p53, alpha-enolase, and Bcl-2. Multivariate analysis showed that TNM stage, cytoplasmic PADI2, and PADI4 remained independent prognostic factors in CRC. Both PADI2 and PADI4 are good prognostic factors in CRC. <b><i>Conclusion:</i></b> High expression of cytoplasmic PADI2, PADI4, and nuclear PADI4 were associated with an increase in overall survival.

Prognostic factors in duodenal adenocarcinoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15797-e15797
Author(s):  
Brandon M Huffman ◽  
Zhaohui Jin ◽  
Cristobal T. Sanhueza ◽  
Mindy L. Hartgers ◽  
Benny Johnson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Lymph Node ◽  
Tumor Invasion ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Clinical Staging ◽  
Lymph Node Status ◽  
Duodenal Adenocarcinoma

e15797 Background: Duodenal adenocarcinoma is a rare tumor representing approximately 0.3% of all gastrointestinal tract cancers. Prognostic factors in relation to survival outcomes for these patients are sporadically reported in the medical literature. We aimed to evaluate outcomes of patients with duodenal adenocarcinoma who underwent pancreaticojejunostomy treated at Mayo Clinic Rochester from January 1, 2006 to December 31, 2016. Methods: Clinicopathological data of 52 duodenal cancer patients were collected. JMP software was used for statistical analysis. Kaplan-Meier method and log-rank tests were used for survival analysis, and multivariate cox proportional hazards model was used to evaluate the prognostic effect of pertinent clinical variables. All tests were two sided and a P value of < 0.05 was considered significant. Results: The median age at diagnosis was 65.9 years (range 39-81). The median overall survival was 51 months (95% CI 31.3-105.4) and the median progression free survival was 30.4 months with median follow up of 73.4 months. There were 3, 9, 21, and 19 patients with stage I, II, III, and IV disease, respectively. Depth of tumor invasion (p = 0.0156) and lymph node metastasis (p = 0.0441) were associated with overall survival on multivariate analysis. Advanced clinical staging influenced overall survival in univariate analysis, but lost prognostic significance in multivariate analysis. Age, gender, surgical technique, presence of metastases, tumor size, number of lymph nodes removed, location of duodenal segment involvement, and adjuvant treatment had no significant impact on overall survival. Laparoscopic approach did not influence survival but was associated with less hospital days (p = 0.0437). Conclusions: Depth of tumor invasion and lymph node status were associated with improved overall survival in patients with duodenal adenocarcinoma. Laparoscopic procedure decreased the hospital stay without affecting outcomes.

scholarly journals Prognostic significance of SDF-1 in colorectal cancer depends on CD8+ T-cell density

2020 ◽  
Author(s):  
Alexandros Lalos ◽  
Ali Tülek ◽  
Nadia Tosti ◽  
Robert Mechera ◽  
Alexander Wilhelm ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
T Cells ◽  
T Cell ◽  
Cell Density ◽  
Cd8 T Cells ◽  
Prognostic Significance ◽  
Cd8 T Cell ◽  
High Expression ◽  
Prognostic Impact

Abstract Background: Since colorectal cancer (CRC) remains one of the most common malignancies, a tremendous amount of studies keep taking place in this field. Over the past 25 years, a notable part of the scientific community has focused on the association between the immune system and colorectal cancer. A variety of studies have shown that high densities of infiltrating CD8+ T cells are associated with improved disease-free and overall survival in colorectal cancer (CRC). Stromal cell-derived factor-1 (SDF-1) is a protein that regulates leukocyte trafficking and is variably expressed in several healthy and malignant tissues. There is strong evidence that SDF-1 has a negative prognostic impact on colorectal cancer (CRC). However, based on a significant correlation of SDF-1 and CD8+ T cells in a previous study (r=0.53, p<0.0001), we hypothesized that the prognostic significance of SDF-1 in CRC could depend on the immune microenvironment. Therefore, we explored the combined prognostic significance of SDF-1 expression and CD8+ T cell density in a large CRC collective. Methods: We analyzed a tissue microarray (TMA) of 613 patient specimens of primary CRCs by immunohistochemistry (IHC) for the expression of SDF-1 by tumor cells and tumor-infiltrating immune cells (TICs) and CD8+ T-cells. Besides, we analyzed the expression of SDF-1 at the RNA level in The Cancer Genome Atlas cohort (TCGA). Results: We found that the the combined high expression of SDF-1 and CD8+ T-cell infiltration shows a favorable 5-year overall survival rate (66%; 95%CI=48–79%) compared to tumors showing a high expression of CD8+ T-cells only (55%; 95%CI=45–64%; p=0.0004). High expression of SDF-1 and CD8+ T-cells infiltration was significantly associated with a favorable prognosis also in a validation group (p=0.016). Univariate and multivariate Hazard Cox regression survival analysis considering the combination of both markers revealed that the combined high expression of SDF-1 and CD8+ T cells was an independent, favorable, prognostic marker for overall survival (HR=0.34, 95%CI=0.17–0.66; p=0.002 and HR=0.45, 95%CI=0.23–0.89; p=0.021, respectively). In a spearman’s correlation analysis from the TCGA cohort, SDF-1 also correlated significantly with CD8+ T cells (r=0.28). Conclusions: SDF-1 high /CD8 high density represents an independent, favorable, prognostic condition in CRC, most likely due to an effective antigen-specific immune response.

Breast Cancer Survival in Relation to the Metastatic Tumor Burden in Axillary Lymph Nodes

2010 ◽  
Vol 28 (17) ◽  
pp. 2868-2873 ◽  
Author(s):  
Yvette Andersson ◽  
Jan Frisell ◽  
Maria Sylvan ◽  
Jana de Boniface ◽  
Leif Bergkvist
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Tumor Cells ◽  
Prognostic Significance ◽  
Axillary Lymph Nodes ◽  
Lymph Node Status ◽  
Axillary Lymph ◽  
Isolated Tumor Cells ◽  
Node Negative ◽  
Survival Difference

Purpose The aim of this study was to determine the prognostic significance of lymph node micrometastases in patients with breast cancer. Patients and Methods Between September 2000 and January 2004, 3,369 patients with breast cancer were included in a prospective cohort. According to their lymph node status, they were classified in the following four groups: 2,383 were node negative, 107 had isolated tumor cells, 123 had micrometastases, and 756 had macrometastases. Median follow-up time was 52 months. Kaplan-Meier estimates and the multivariate Cox proportional hazard regression model were used to analyze survival. Results Five-year cause-specific and event-free survival rates were lower for patients with micrometastases (pN1mi) than for node-negative (pN0) patients (94.1% v 96.9% and 79.6% v 87.1%, respectively; P = .020 and P = .032, respectively). There was no significant survival difference between node-negative patients and those with isolated tumor cells. The overall survival of pN1mi and pN0 patients did not differ. Conclusion This study demonstrates a worse prognosis for patients with micrometastases than for node-negative patients.

scholarly journals Thioredoxin system protein expression in carcinomas of the pancreas, bile duct and ampulla.

2019 ◽  
Author(s):  
Khaled S. Al-hadyan ◽  
Sarah J. Storr ◽  
Abed M. Zaitoun ◽  
Dileep N. Lobo ◽  
Stewart G. Martin
Keyword(s):  
Overall Survival ◽  
Lymph Node ◽  
Bile Duct ◽  
Protein Expression ◽  
Cox Regression ◽  
Venous Invasion ◽  
High Expression ◽  
Lymph Node Status ◽  
Confounding Factors ◽  
Tumour Grade

Abstract Background: Pancreatic cancer (PC), including the ampulla and bile duct, is very aggressive, and thus difficult to treat with effective therapies. The current treatment options have failed to improve PC five-year survival rates over the last 30 to 40 years, which remain very low, at ~3%; there is, therefore, an urgent need to identify new targets and treatment modalities (1). Methods: The protein expression of thioredoxin (Trx), thioredoxin reductase (TrxR) and thioredoxin interacting protein (TxNIP) was assessed in two cancer patient cohorts by standard immunohistochemistry using tissue microarrays. The first cohort was composed of 85 pancreatic adenocarcinomas (PAD) and the second of 145 cancers of the bile duct and ampulla. Results: In the PAD cohort, high cytoplasmic TrxR expression significantly associated with lymph node metastasis (P = 0.033). High expression of cytoplasmic (P = 0.018) and nuclear (P = 0.006) Trx were significantly associated with better overall survival, with nuclear Trx expression remaining significantly associated with survival in multivariate Cox-regression (Hazard Ratio (HR) 0.316; 95% Confidence Interval (95% CI) 0.174-0.573; P < 0.0001) when potentially confounding factors were included (gender, age, tumour size, tumour grade, tumour stage, lymph node status, perineural and venous invasion). In cancers of the bile duct and ampulla, high expression of nuclear TrxR and high cytoplasmic TxNIP were associated with patients aged above 60 years (P = 0.024 and P = 0.049 respectively). Associations were also observed between high nuclear TrxR expression and the presence of venous (P = 0.001) and perineural (P = 0.021) invasion. Low cytoplasmic TxNIP expression was also associated with the presence of perineural invasion (P = 0.025). High expression of cytoplasmic TxNIP was significantly associated with better overall survival (P = 0.0002), which remained significant in multivariate Cox-regression analysis (HR 0.548; 95% CI 0.340-0.882; P = 0.013) when potentially confounding factors were included (tumour grade, stage, lymph node status, perineural and venous invasion). Conclusion: Current findings demonstrate the prognostic importance of Trx system protein expression in pancreatic, bile duct and ampullary cancers, with expression of certain members potentially being involved in disease progression. Current findings warrant a larger follow-up study.

NOTCH1 as a potential prognostic biomarker for anti-VEGF therapy in patients with metastatic colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11038-11038
Author(s):  
Tadeu Ferreira Paiva ◽  
Alexandre Andre Balieiro Anastacio da Costa ◽  
Flavio Augusto Ismael Pinto ◽  
Victor Hugo Fonseca Jesus ◽  
Raul A. Marques ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Lymph Node ◽  
Liver Metastasis ◽  
Lymph Node Metastasis ◽  
Metastatic Colorectal Cancer ◽  
Response Rate ◽  
High Expression ◽  
Node Metastasis

11038 Background: There are no validated biomarkers for clinical response or survival benefit in patients treated with bevacizumab (Bv) in advanced metastatic colorectal cancer (mCRC). The aim of this study was to evaluate the predictive value of putative biomarkers in mCRC. Methods: One hundred and five mCRC patients who received Bv combined with FOLFOX or FOLFIRI were retrospectively evaluated for clinical and pathological characteristics. VEGFR1, VEGFR2, VEGFR3, PlGF, DLL4 and NOTCH1 expression were assessed by immunohistochemistry on formalin-fixed, paraffin-embedded neoplastic tissue of either primary or metastatic tissue in a tissue microarray. High levels of expression were defined as less than or equal to or more than the median. Survival curves were calculated by the Kaplan-Meier method and compared by the log-rank test. For multivariate analysis the Cox proportional hazards model was used. Results: Grade 1 or 2 (p=0.01), non-mucin-producing histology (p=0.04) and presence of liver metastasis (p=0.001) were associated with a higher response rate. There was no difference between the expression of markers and the response rate. ECOG 0 or 1 (p=0.002), grade 1 or 2 (p=0.02), liver metastasis (p=0.003), no lymph node metastasis (p=0.01) no peritoneal metastasis (p=0.02) and resection of metastasis (p<0.001) were correlated with higher progression-free survival (PFS). There was also a strong correlation between ECOG 0 or 1 (p=0.001), grade 1 or 2 (p=0.006), no lymph node metastasis (p=0.004), liver metastasis (p<0.001) and resection of metastasis (p<0.0001) with better overall survival. There was a trend between high expression of NOTCH1 (p=0.06) and worst PFS.High expression of VEGFR2 (p=0.07) was slightly associated with a better overall survival, while high expression of NOTCH1 was associated with a worse overall survival (p=0.01). Using multivariate analysis, NOTCH1 proved to be an independent variable for adverse overall survival (HR 2.01, IC 1.07 – 3.77, p=0.02). Conclusions: High NOTCH1 expression assessed by immunohistochemistry is capable of predicting poor survival in advanced colorectal cancer patients treated with bevacizumab.

Expression and prognostic significance of ECT2 in invasive breast cancer

2017 ◽  
Vol 71 (5) ◽  
pp. 442-445 ◽  
Author(s):  
Hong-kun Wang ◽  
Jian-fang Liang ◽  
Hui-xia Zheng ◽  
Hong Xiao
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Triple Negative ◽  
Prognostic Significance ◽  
High Expression ◽  
Proliferation Index ◽  
Ki 67 ◽  
Node Metastasis

AimsTo investigate the expression of epithelial cell transforming sequence 2 (ECT2) in invasive breast cancer and its prognostic significance.MethodsECT2 immunohistochemical detection was performed in 165 breast cancer specimens and 100 normal control tissues. Univariable and multivariable Cox proportional hazards regression model analysis was used to confirm independent prognostic factors. The PHREG procedure linear hypotheses testing method was used to analyse survival data.ResultsExpression of ECT2 in breast cancer was significantly higher than that of the normal control group (p<0.001), and it was related to tumour grade, the status of lymph node metastasis, TNM staging, recurrence status, menopausal status, and the Ki-67 proliferation index (p<0.05), and not related to age, tumour size, tumour type, expression of estrogen receptor, progesterone receptor and human epidermal growth factor 2, and triple-negative disease (p>0.05). Univariable analysis showed that expression of ECT2, the status of lymph node metastasis, triple-negative disease and Ki-67 proliferation index were related to the overall survival of patients with breast cancer (p<0.001, p=0.006, p=0.001, p=0.041, respectively). PHREG procedure linear hypotheses testing results for overall survival revealed that high expression of ECT2, lymph node metastasis, triple-negative disease and high Ki-67 proliferation index predicted lower overall survival rates. Multivariable Cox regression indicated that high expression of ECT2 and triple-negative disease were independent prognostic factors for patients with breast cancer (p<0.001, p=0.004, respectively).ConclusionsExpression of ECT2 may be one of the main causes of the occurrence and development of breast cancer, and high expression of ECT2 as an independent prognostic factor predicts a poor prognosis. ECT2 could also be a potential molecular target for designing therapeutic strategies for breast cancer.

scholarly journals Clinicopathological Significance of Mesothelin Expression in Invasive Breast Cancer

2012 ◽  
Vol 40 (3) ◽  
pp. 909-916 ◽  
Author(s):  
L Wang ◽  
Z Niu ◽  
L Zhang ◽  
X Liu ◽  
X Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Breast Carcinoma ◽  
Invasive Breast Cancer ◽  
Tumour Size ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
Tumour Cells ◽  
Lymph Node Status

OBJECTIVES: This study evaluated the expression profile of the mesothelin ( MSLN) gene and its prognostic significance in breast cancer. METHODS: To evaluate the diagnostic and prognostic significance of mesothelin, immunohistochemistry was used to assess the level of mesothelin protein in surgically resected, formalin-fixed, paraffin-embedded invasive breast carcinoma specimens. Associations between mesothelin and other biomarkers, including oestrogen receptor (OR), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2/neu), were also evaluated. RESULTS: A total of 182 breast carcinoma specimens were included. Mesothelin protein was present in the membrane of malignant cells. There was correlation between the presence of mesothelin in tumour cells and tumour infiltration of the lymph node. There was no correlation between the presence of mesothelin and HER2/neu protein, OR and PR in tumour cells. Mesothelin levels were significantly associated with decreased overall survival. CONCLUSIONS: Lymph node status, tumour size, HER2/neu and mesothelin protein levels in breast cancer cells were independent prognostic factors. Mesothelin could be useful as a prognostic marker of overall survival in invasive breast cancer.

Prognostic significance of metastatic cascade in melanoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19029-e19029
Author(s):  
Travis Brad Kidner ◽  
Jeong Lim Yoon ◽  
Mark B. Faries ◽  
Donald L. Morton
Keyword(s):  
Overall Survival ◽  
Lymph Node ◽  
Prognostic Factor ◽  
Lymph Nodes ◽  
Pulmonary Resection ◽  
Mediastinal Lymph Node ◽  
Prognostic Significance ◽  
Lymph Node Status ◽  
Regional Lymph Nodes ◽  
Metastatic Cascade

e19029 Background: The ability of metastases to spawn subsequent generations of metastatic lesions is controversial, and its prognostic significance is unknown. We hypothesize that melanoma metastases that have spread to draining lymph nodes will have a worse prognosis than those that have not. Methods: One hundred consecutive patients who had undergone pulmonary resection for metastatic melanoma and who had concomitant hilar and/or mediastinal lymph node evaluation available were identified. Patient demographics, tumor characteristics, mediastinal lymph node status, and overall survival were analyzed. Results: 100 patients (71%) were male and the mean age at metastasectomy was 55 years (mean age at diagnosis 47 years.) The average Breslow thickness was 2.43mm (range 0.46 – 20.55). Twenty-one (21%) of the patients had evidence of metastatic disease present in regional lymph nodes during pulmonary resection. The 5-year overall survival for patients with positive mediastinal lymph nodes was 16% versus 36% with node negative disease (p=0.0005). On multivariate analysis, age at pulmonary resection (HR 1.018, 95% CI 1.002-1.035) and regional lymph nodes status (HR 3.203, 95% CI 1.774-5.781) were found to be independent prognostic indicators of 5-year overall survival. Conclusions: Regional lymph node status is an important prognostic factor in patients with pulmonary metastatic melanoma, and regional nodal assessment should be considered during metastasectomy. The metastatic cascade appears to be a strong prognostic factor in melanoma.

Sentinel Node Biopsy: Interpretation and Management of Patients With Immunohistochemistry-Positive Sentinel Nodes and Those With Micrometastases

2008 ◽  
Vol 26 (5) ◽  
pp. 698-702 ◽  
Author(s):  
Emiel J.T. Rutgers
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Sentinel Node ◽  
Tumor Cells ◽  
Clinical Decision Making ◽  
Prognostic Significance ◽  
Axillary Lymph ◽  
Isolated Tumor Cells ◽  
Sentinel Nodes ◽  
Node Metastasis

The sentinel node procedure is an adequate tool to identify lymph node metastasis in breast cancer. Sentinel nodes are generally examined with greater attention mainly to exclude, as reliably as possible, lymph node metastasis. To achieve this, many protocols are used, resulting in different rates of micrometastasis or isolated tumor cells encountered. Since the prognostic significance of isolated tumor cells or micrometastasis in the sentinel nodes, and the risk of further axillary lymph node involvement in patients with isolated tumor cells, is uncertain and at most limited, these findings may pose difficulties for clinicians in clinical decision making. Protocols that identify lymph node metastasis, from which the clinical relevance is known, are warranted. Unnecessary lymph node dissections should be avoided.

Sign in / Sign up

Export Citation Format

Share Document