Prognostic significance of tumor-induced angiogenesis in colorectal cancer

Introduction Tumor-induced angiogenesis is a central pathogenic step in the process of tumor growth, invasion and metastasis. The aim of this study was to analyze the quantitative expression of angiogenesis in colorectal carcinoma and to determine if and how angiogenesis correlates with other clinicopathologic factors and prognosis. Material and methods This study included 40 patients who underwent curative resection of colorectal cancer at the Department of Surgery of the Senta General Hospital with complete 5 years follow-up or till death. Microvessels were identified immunohistochemically using monoclonal CD31 antibodies. The microvessel count was assessed by means of stereology with test grid M42, as well as vascular surface density in the stromal volume at the invasive front of colorectal cancer. Results Tumor-induced angiogenesis count of colorectal carcinomas statistically significantly correlated with stage of disease and histologic tumor grade There was no significant correlation between intratumoral microvessel density and sex and age of patients, localization and histologic tumor type Five-year survival rate in patients with hypervascular colorectal tumors was statistically significantly lower than in patients with hypovascular tumors Thus, microvessel density in colorectal cancer is an independent prognostic factor, but its significance is less than the importance concerning stage of disease and histologic grade of tumor. Conclusions Intratumoral microvessel density quantification in histologic specimens of colorectal carcinoma reflects the biological malignant potential of tumors and may be a useful additional predictive marker. Assessment of intratumoral microvessel count might be used for determining the pathologic stage when adjuvant therapy is concerned. Microvessel density in tumor specimens is valuable in stratifying patients in planning appropriate adjuvant and antiangiogenic therapy after surgery.

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Study of Microvessel Density and the Expression of Vascular Endothelial Growth Factors in Adrenal Gland Pheochromocytomas

International Journal of Endocrinology ◽

10.1155/2014/104129 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Magdalena Białas ◽

Grzegorz Dyduch ◽

Joanna Dudała ◽

Monika Bereza-Buziak ◽

Alicja Hubalewska-Dydejczyk ◽

...

Keyword(s):

Growth Factors ◽

Microvessel Density ◽

Antiangiogenic Therapy ◽

Prognostic Significance ◽

Operation Technique ◽

Vascular Endothelial Growth Factors ◽

Vascular Endothelial ◽

Vascular Architecture ◽

Laparoscopic Operation ◽

Endothelial Growth Factors

Angiogenesis (neoangiogenesis), a process of neovascularization, is an essential step for local tumor growth and distant metastasis formation. We have analysed angiogenesis status: vascular architecture, microvessel density, and vascular endothelial growth factors expression in 62 adrenal pheochromocytomas: 57 benign and 5 malignant. Immunohistochemical evaluation revealed that vascular architecture and vessel density are different in the central and subcapsular areas of the tumor. Furthermore, we have observed a strong correlation between number of macrophages and microvessel density in the central and subcapsular areas of the tumor and between the expression of VEGF-A in tumor cells and microvessel density in central and subcapsular areas of the tumor. Secondary changes in these tumors influence the results and both vascular architecture and microvessel density are markedly disturbed by hemorrhagic and cystic changes in pheochromocytomas. These changes are partially caused by laparoscopic operation technique. However, no differences in vascular parameters were found between pheochromocytomas with benign and malignant clinical behavior. Our observation showed that analysis of angiogenesis, as a single feature, does not help in differentiating malignant and benign pheochromocytomas and has no independent prognostic significance. On the other hand, high microvessel density in pheochromocytoma is a promising factor for antiangiogenic therapy in malignant cases.

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PROPHYLAXIS AND TREATMENT OF SIDE EFFECTS OF ANTIANGIOGENIC THERAPY IN PATIENTS WITH METASTATIC COLORECTAL CARCINOMA

Russian Journal of Oncology ◽

10.18821/1028-9984-2017-22-3-164-168 ◽

2017 ◽

Vol 22 (3) ◽

pp. 164-168

Author(s):

Andrey A. Meshcheryakov

Keyword(s):

Colorectal Cancer ◽

Side Effects ◽

Colorectal Carcinoma ◽

Metastatic Colorectal Cancer ◽

Personal Experience ◽

Antiangiogenic Therapy ◽

Metastatic Colorectal Carcinoma ◽

Angiogenic Therapy ◽

Prevention And Treatment

The review analyzed data from the literature and personal experience of the application of anti-angiogenic therapy in metastatic colorectal cancer. There are presented practical advices on prevention and treatment of the most common side effects of anti-angiogenic therapy.

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Claudin-1 Is a Valuable Prognostic Biomarker in Colorectal Cancer: A Meta-Analysis

Gastroenterology Research and Practice ◽

10.1155/2020/4258035 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Didi Zuo ◽

Jiantao Zhang ◽

Tao Liu ◽

Chao Li ◽

Guang Ning

Keyword(s):

Colorectal Cancer ◽

Meta Analysis ◽

Prognostic Significance ◽

Disease Free Survival ◽

Venous Invasion ◽

Lymphatic Invasion ◽

Cochrane Library ◽

Test Sequence ◽

Tumor Type ◽

The Stability

Background. Claudin-1 plays an important part in maintaining the mucosal structures and physiological functions. Several studies showed a relationship between claudin-1 and colorectal cancer (CRC), but its prognostic significance is inconsistent. This meta-analysis assessed the prognostic value and clinical significance of claudin-1 in CRC. Materials and Methods. We retrieved eligible studies from PubMed, Cochrane Library, Embase, and Web of Science databases before February 10, 2020. The hazard ratio (HR) with 95% confidence interval (CI) was applied to assess the correlation between claudin-1 and prognosis and clinical features. Heterogeneity was assessed by the Cochran Q test and I-square (I2), while publication bias was evaluated by the Begg test and Egger test. Test sequence analysis (TSA) was used to estimate whether the included studies’ number is sufficient. The stability of the results was judged by sensitivity analysis. Metaregression was utilized to explore the possible covariance which may impact on heterogeneity among studies. Results. Eight studies incorporating 1704 patients met the inclusion criteria. Meta-analysis showed that the high expression of claudin-1 was associated with better overall survival (HR, 0.46; 95% CI, 0.28–0.76; P=0.002) and disease-free survival (HR, 0.44; 95% CI, 0.29–0.65; P=0.003) in CRC. In addition, we found that claudin-1 was related to the better tumor type (n=6; RR, 0.60; 95% CI, 0.49–0.73; P<0.00001), negative venous invasion (n=4; RR, 0.81; 95% CI, 0.70–0.95; P=0.001), and negative lymphatic invasion (n=4; RR, 0.83; 95% CI, 0.74–0.92; P=0.0009). Conclusion. The increased claudin-1 expression in CRC is associated with better prognosis. In addition, claudin-1 was related to the better tumor type and the less venous invasion and lymphatic invasion.

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Antiangiogenic Therapy of Colorectal Cancer: State of the Art, Challenges and New Approaches

The International Journal of Biological Markers ◽

10.5301/jbm.2012.10441 ◽

2012 ◽

Vol 27 (4) ◽

pp. 286-294 ◽

Cited By ~ 4

Author(s):

Roberta Sarmiento ◽

Raffaele Longo ◽

Giampietro Gasparini

Keyword(s):

Colorectal Cancer ◽

Review Paper ◽

Advanced Colorectal Cancer ◽

State Of The Art ◽

Antiangiogenic Therapy ◽

Clinical Results ◽

Controversial Issues ◽

Tumor Type ◽

Antiangiogenic Agent ◽

Adjuvant Setting

Advanced colorectal cancer is the first tumor type for which an antiangiogenic agent, namely bevacizumab, has been approved by the Food and Drug Administration for therapy in humans; it has been in use since February 2004. This review paper summarizes and discusses the results obtained with this agent and highlights the main open or controversial issues on antiangiogenic therapy, taking into account that the clinical results obtained are below the expectations, particularly in the adjuvant setting.

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A Retrospective Descriptive Study of Pattern and Presentation of Colorectal Cancers in Shaikh Zayed Hospital Lahore

10.53350/pjmhs2115112993 ◽

2021 ◽

Vol 15 (11) ◽

pp. 2993-2995

Author(s):

Muhammad Aamir Jameel ◽

Muhammad Imran Anwar ◽

Muhammad Muaaz Akram ◽

Haroon javid Majid ◽

Sameen Tahir

Keyword(s):

Colorectal Cancer ◽

Colorectal Carcinoma ◽

Tertiary Care ◽

Age Groups ◽

Case Series ◽

Tumor Grade ◽

Care Hospital ◽

Clinical Presentations ◽

Case Series Study ◽

Study Methodology

Aim: To determine the distribution of gender, age and clinical presentations along with histological type of colorectal cancer in patients presented to Shaikh Zayed Hospital Lahore. Study design: This is a case series study Methodology: This retrospective study on colorectal cancer was conducted in Shaikh Zayed Hospital Lahore. Forty-four 44 patients from Jan 2018 to Jan 2021 were included of colorectal carcinoma. Data were collected and analyzed using SPSS v 23 retrospectively from hospital record. Results: 15.9% of the patients were below the age of 30 years, 31.8% were below 40 years. Male were 65.9%. Commonest presenting symptom was altered bowel habits, rectal bleeding along with weight loss and the dominating tumor grade was moderately differentiated adenocarcinoma. Conclusion: In this study colorectal carcinoma among young age groups were more commonly present at the fourth and sixth decade. Keywords: Colorectal carcinoma, Adenocarcinoma, Tertiary care hospital.

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Prognostic Value of Circulating KRAS2 Gene Mutations in Colorectal Cancer with Distant Metastases

The International Journal of Biological Markers ◽

10.1177/172460080602100405 ◽

2006 ◽

Vol 21 (4) ◽

pp. 223-228 ◽

Cited By ~ 20

Author(s):

C. Trevisiol ◽

F. Di Fabio ◽

R. Nascimbeni ◽

L. Peloso ◽

C. Salbe ◽

...

Keyword(s):

Colorectal Cancer ◽

Colorectal Carcinoma ◽

Residual Disease ◽

Prognostic Significance ◽

Primary Treatment ◽

Tissue Samples ◽

Primary Tumors ◽

Mutational Status ◽

Stage D ◽

Related Survival

While tissue KRAS2 mutations have been extensively investigated, the role of circulating mutant KRAS2 gene in patients with colorectal carcinoma remains obscure. The aim of the present study was to explore the prognostic significance of circulating KRAS2 gene mutational status in subjects undergoing primary treatment for colorectal cancer. Codon 12 KRAS2 mutations were examined in DNA samples extracted from the serum of 86 patients with colorectal cancer and were compared with the KRAS2 status of their primary tumors. Tissue and serum KRAS2 status was compared with other clinicopathological variables (including CEA and CA 19-9 levels) and with cancer-related survival. KRAS2 mutations were found in tissue samples of 28 patients (33%); serum KRAS2 mutations were detected in 10 of them (36%). Serum KRAS2 status was significantly associated with Dukes' stage D (p=0.001) and with preoperative CA 19-9 levels (p=0.01). At multivariate analysis, cancer-related survival was associated with Dukes' stage (p<0.0001), CEA level (p=0.02), and mutant circulating KRAS2 (p=0.01). All 7 stage D patients with serum KRAS2 mutations died of the disease within 24 months of primary treatment; cancer-related survival was significantly better in 9 stage D patients without serum KRAS2 mutations, with 5 patients (56%) alive after 24 months and 1 patient (13%) alive after 44 months. Residual disease after surgery was evident in all 7 stage D patients with mutant circulating KRAS2, and in 5 out of 9 stage D patients without serum mutations. Serum KRAS2 status may impact substantially on the management of stage D colorectal carcinoma, since it appears to correlate with prognosis in this patient subgroup.

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The Prognostic Significance of Hsp70 in Patients with Colorectal Cancer Patients: A PRISMA-Compliant Meta-Analysis

BioMed Research International ◽

10.1155/2021/5526327 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Guangyu Gao ◽

Songtao Liu ◽

Zhen Yao ◽

Yanyan Zhan ◽

Wenyue Chen ◽

...

Keyword(s):

Colorectal Cancer ◽

Colorectal Carcinoma ◽

Cancer Patients ◽

Web Of Science ◽

Meta Analysis ◽

Prognostic Significance ◽

Expression Level ◽

Hsp70 Expression ◽

Colorectal Cancer Patients ◽

The Relationship

Background. Hsp70 (heat shock protein 70) plays a key role in carcinogenesis and cancer progression. However, the relationship between the Hsp70 expression level and the colorectal cancer patient survival is unknown. This study is aimed at investigating the relationship between Hsp70 and the prognosis of colorectal carcinoma patients. Methods. PubMed, Web of Science, and Embase were used for systematic computer literature retrieval. Stata SE14.0 software was used for quantitative meta-analysis. Besides, data was extracted from selected articles. Relationships between Hsp70 expression level and prognosis were further studied. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were also computed. Results. A total of 11 potentially eligible studies with 2269 patients were identified in 10 tumors from PubMed, Web of Science, and Embase. Hsp70 overexpression was associated with poor overall survival (OS) and disease-free survival (DFS) in colorectal carcinoma patients (HRs, 0.65 (95% CI: 0.52-0.78) and 0.77 (95% CI: 0.23-1.32), respectively). Conclusions. Hsp70 overexpression can predict poor survival in colorectal cancer patients.

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Immunohistochemical expression of clusterin in colorectal carcinoma

Zanco Journal of Medical Sciences ◽

10.15218/zjms.2021.018 ◽

2021 ◽

Vol 25 (2) ◽

pp. 544-550

Author(s):

Jalal Jalal ◽

Zheen Othman ◽

Payman Anwar

Keyword(s):

Colorectal Cancer ◽

Colorectal Carcinoma ◽

Colorectal Adenocarcinoma ◽

Clinicopathological Characteristics ◽

Clinicopathological Parameters ◽

Normal Colonic Mucosa ◽

Tumor Type ◽

Keywords Colorectal Cancer ◽

Wide Range ◽

Clusterin Expression

Background and objective: Colorectal cancer is a heterogeneous malignancy characterized by a wide range of genetic and epigenetic alterations. Clusterin is a heterodimeric glycoprotein widely expressed in a variety of tissues and secreted in many body fluids. Increased clusterin expression has been reported in the normal colonic mucosa, benign polyps, and colorectal carcinoma. This study aimed to detect the frequency of the clusterin immunoexpression in colorectal carcinoma and determine its association with some clinicopathological parameters. Methods: Sixty formalin-fixed paraffin-embedded sections of colorectal adenocarcinoma were obtained and randomly selected from the histopathology laboratory at Rizgary Teaching Hospital and some private histopathology laboratories in Erbil city over two years between December 2016 and December 2018. All patients had been diagnosed to have primary colorectal adenocarcinoma and had undergone surgery. The clinicopathological characteristics of the tumors were revised, and the specimens were analyzed immunohistochemically using anticlusterin mouse monoclonal antibody. Results: Twenty eight cases (46.6%) were labeled as clusterin positive, while 32 cases (53.4%) were negative for clusterin expression. Clusterin expression was significantly associated with the tumor type (Non-mucinous) (P = 0.01) and tumor grade (well to moderately differentiated) (P = 0.03). At the same time, no significant association was found between clusterin immunoexpression and other clinicopathological characteristics like age, gender, tumor site, and tumor stage. Conclusion: Our study indicated that clusterin is overexpressed in some colorectal carcinomas and is significantly associated with histological type and grade. These results suggest that clusterin may play a role in colorectal carcinogenesis. Further studies are required to understand the possible mechanism of clusterin association with carcinogenesis and cancer progression. Keywords: Colorectal cancer; Clusterin; Immunohistochemistry.

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Clinical implications of microsatellite instability in mucinous colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.657 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 657-657

Author(s):

Fergus Keane ◽

Darrell Martin ◽

Gregory D. Leonard ◽

Sean Hynes ◽

Margaret Sheehan

Keyword(s):

Colorectal Cancer ◽

Microsatellite Instability ◽

Who Classification ◽

Prognostic Significance ◽

Stage Ii ◽

Stage Iii ◽

Low Grade ◽

Tumor Type ◽

Response To Chemotherapy ◽

Microsatellite Stability

657 Background: Colorectal Cancer(CRC) is becoming increasingly recognised as a heterogeneous tumor type. Mucinous histological subtype is identified in 10-15% of CRCs, most commonly those with microsatellite instability (MSI), and has traditionally been associated with unfavorable outcomes and poor response to chemotherapy. In contrast, MSI is associated with relatively favourable pathological features and better outcomes, compared with CRCs with microsatellite stability (MSS), such that under the 2010 WHO classification, MSI mucinous CRC is considered low grade, while MSS mucinous CRC is classified as high grade. The aim of this study is to establish the significance of microsatellite stability status in non-metastatic mucinous colorectal cancer. Methods: Between 2010 and 2017, 69 patients with stage II or stage III mucinous colorectal cancer were identified. Microsatellite status was tested in all patients (MSS or MSI), and histological and clinical data, as well as recurrence rates, were assessed in both groups. MSI status was established using polymerase chain reaction(PCR) technique. Results: Sixty-nine patients with mucinous CRC were identified. The median age for the entire group was 73 years (range 32-87), no difference in gender was identified. 63%(n=43) and 37%(n=26) were stage II and stage III respectively at diagnosis. The majority of mucinous CRCs were right-sided (72%). 33% (n=23) were identified as microsatellite unstable (MSI). MSI status was associated with right sided tumours (78% right-sided vs 22% left-sided, p<0.05), older age at diagnosis (mean 76 years vs 68 years, p=0.01), and lower TNM staging at diagnosis (83% vs 52% diagnosed stage 2, p=0.007) compared with the MSS group. A lower disease recurrence rate was identified in the MSI group (4.3% vs 13% in MSS group) at median follow-up time of 33 months (range 8-93 months). Conclusions: In patients with mucinous colorectal cancer, MSI status is a useful marker of favourable histological and clinical features, and is associated with better outcomes. Our study supports the current 2010 WHO classification, and highlights the clinical and prognostic significance of MSI status in this patient cohort.

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Subcellular localization of HMGB1 in colorectal cancer impacts on tumor grade and survival prognosis

Scientific Reports ◽

10.1038/s41598-020-75783-2 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Chao-Qun Wang ◽

Bi-Fei Huang ◽

Yan Wang ◽

Chih-Hsin Tang ◽

Hong-Chuan Jin ◽

...

Keyword(s):

Colorectal Cancer ◽

Colorectal Adenoma ◽

Prognostic Significance ◽

Tumor Grade ◽

Hmgb1 Protein ◽

Survival Prognosis ◽

Tissue Samples ◽

Colorectal Tissue ◽

Hmgb1 Expression ◽

Normal Colorectal Tissue

Abstract The high-mobility group box-1 (HMGB1) protein is implicated in the development of various cancers and their proliferation. According to its function, HMGB1 shuttles between the cell nucleus and cytoplasm, assisting with nucleosome stabilization and gene transcription, or localizing in the cell membrane for outgrowth. The clinicopathologic and prognostic significance of these different subcellular locations and their correlation has been unclear in colorectal cancer (CRC). We found significantly higher rates of nuclear HMGB1 expression in CRC and colorectal adenoma tissue samples (84.0% and 92.6%, respectively) than in normal colorectal tissue (15.0%) and a significantly higher rate of positive cytoplasmic HMGB1 expression in CRC tissue (25.2%) compared with colorectal adenoma (11.8%) and normal colorectal tissue (0.0%). Positive cytoplasmic HMGB1 expression was associated with high-grade CRC, a poor prognosis, and was negatively correlated with strongly positive nuclear HMGB1 expression in CRC tissue specimens (r = – 0.377, P = 0.000). CRC patients with strongly positive nuclear HMGB1 expression had a better survival prognosis than other CRC patients. Preventing nuclear plasma translocation of HMGB1 may be a new strategy for CRC management.

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