Vascular endothelial growth factor, CD68, and epidermal growth factor receptor expression and survival in patients with Stage II and Stage III colon carcinoma

Khorana, Alok A.; Ryan, Charlotte; Cox, Christopher; Eberly, Shirley; Sahasrabudhe, Deepak M.

doi:10.1002/cncr.11152

Cited by 143 publications

(104 citation statements)

References 36 publications

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“…In a series of studies, overexpression of VEGF was detected in 45% to 70% of CRCs [21] [35]- [42] which is comparable with the present study. However, Khorana et al reported lower incidence of VEGF immunopositivity (34%) [43] whereas Uner et al showed higher frequency of 86% in CRCs [44]. In the present study, a significant association was observed between VEGF expression and high histological grade tumors.…”

Section: Discussioncontrasting

confidence: 49%

Protein Expression of STAT3, pSTAT3, MMP-7 and VEGF in Colorectal Adenocarcinoma: An Immunohistochemical Study

Naidu¹,

Nee²,

Jw³

et al. 2014

JCT

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Background: The purpose of the present study is to investigate the expression levels of STAT3, pSTAT3, MMP-7 and VEGF in colorectal adenocarcinoma, and also to determine association with the clinico-pathological parameters and co-expression of these genes. Methods: An immunohistochemical method was used to evaluate the expression of MMP-7 and VEGF genes in 93 archival tissues whereas STAT3 and pSTAT3 expression was determined in 75 cases. Results: Overexpression of STAT3 was detected in 26.7% (20/75), pSTAT3 in 13.4% (10/75), MMP-7 in 38.8% (36/93) and VEGF in 59.2% (55/93) of the colorectal carcinomas. STAT3, MMP-7 and VEGF immunopositivity were significantly correlated with poorly-differentiated tumors (P = 0.004; P = 0.03; P = 0.002, respectively) but not with other parameters. However, pSTAT3 immunostaining was not significantly associated with the clinico-pathological characteristics. Significant relationship was noted between overexpression of pSTAT3 and STAT3 (P < 0.001), pSTAT3 and VEGF (P = 0.044), pSTAT3 and MMP-7 (P = 0.003), and STAT3 and VEGF (P = 0.037) but marginal association was detected between STAT3 and MMP-7 (P = 0.057), and MMP-7 and VEGF (P = 0.052). Conclusion: Our data suggest that expression of these genes may have an important role in tumor dedifferentiation and may be useful as indicators of biologic aggressiveness. Co-expression of the bio-* Corresponding author. R. Naidu et al. 1176markers by cancer cells may have important implications in colorectal cancer biology and could be useful biological markers of the malignant phenotype.

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Section: Discussioncontrasting

confidence: 49%

Protein Expression of STAT3, pSTAT3, MMP-7 and VEGF in Colorectal Adenocarcinoma: An Immunohistochemical Study

Naidu¹,

Nee²,

Jw³

et al. 2014

JCT

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“…[12][13][14] Some studies relying on immunohistochemical staining of human colorectal cancers, in fact, indicate that macrophages along the tumor margin [31][32][33] and macrophages expressing VEGF 34 are associated with a good prognosis. Others have suggested that macrophages in colorectal cancer may have co-stimulatory functions in antitumor immunity 35 or may be able to induce tumor cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Stromal CCR6 drives tumor growth in a murine transplantable colon cancer through recruitment of tumor-promoting macrophages

et al. 2016

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Interactions between the inflammatory chemokine CCL20 and its receptor CCR6 have been implicated in promoting colon cancer; however, the mechanisms behind this effect are poorly understood. We have previously demonstrated that deficiency of CCR6 is associated with decreased tumor macrophage accumulation in a model of sporadic intestinal tumorigenesis. In this study, we aimed to determine the role of stromal CCR6 expression in a murine syngeneic transplantable colon cancer model. We show that deficiency of host CCR6 is associated with decreased growth of syngeneic CCR6-expressing colon cancers. Colon cancers adoptively transplanted into CCR6-deficient mice have decreased tumor-associated macrophages without alterations in the number of monocytes in blood or bone marrow. CCL20, the unique ligand for CCR6, promotes migration of monocytes in vitro and promotes accumulation of macrophages in vivo. Depletion of tumor-associated macrophages decreases the growth of tumors in the transplantable tumor model. Macrophages infiltrating the colon cancers in this model secrete the inflammatory mediators CCL2, IL-1a, IL-6 and TNFa. Ccl2, Il1a and Il6 are consequently downregulated in tumors from CCR6-deficient mice. CCL2, IL-1a and IL-6 also promote proliferation of colon cancer cells, linking the decreased macrophage migration into tumors mediated by CCL20-CCR6 interactions to the delay in tumor growth in CCR6-deficient hosts. The relevance of these findings in human colon cancer is demonstrated through correlation of CCR6 expression with that of the macrophage marker CD163 as well as that of CCL2, IL1a and TNFa. Our findings support the exploration of targeting the CCL20-CCR6 pathway for the treatment of colon cancer.

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“…29,30 Recent studies have described a significant association between increased protein levels of EGFR and poor prognosis in patients with CRC. 31,32 However, whether EGFR is a predictive factor, as well as being a prognostic factor, is still unclear. Ling et al showed that in human cervical squamous cancer cells, high EGFR protein expression levels are associated with a greater sensitivity to Topo 1 inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Molecular determinants of irinotecan efficacy

Vallböhmer

Iqbal

Yang

et al. 2006

Intl Journal of Cancer

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Molecular markers predicting the efficacy of CPT‐11 based chemotherapies in patients with colorectal cancer (CRC) are unknown. Therefore, we investigated whether mRNA levels of drug targets (Topoisomerase I, TS), enzymes involved in 5‐FU metabolism (DPD), in angiogenesis (EGFR, IL‐8, VEGF) and in DNA‐repair/drug detoxification (ERCC1, GST‐P1) are associated with the clinical outcome of patients with CRC treated with first‐line CPT‐11 based chemotherapy. Thirty three patients with metastatic CRC were included in the study. Intratumoral gene expression levels were assessed from paraffin‐embedded tissue samples, using laser capture microdissection and quantitative Real‐Time PCR. Complete response was observed in 1 patient, partial response in 12 patients, stable disease in 13 patients and progressive disease in 6 patients. Response was inevaluable for 1 patient. Patients with complete response or partial response were classified as responders, while patients with stable disease or progressive disease were classified as nonresponders. High intratumoral mRNA levels of EGFR, ERCC1 and GSPT‐P1 were each significantly associated with response to CPT‐11 based chemotherapy. Recursive partitioning analysis showed that mRNA levels of EGFR and ERCC1 are primarily responsible for delineating responders from nonresponders. Also, the combination of high intratumoral gene expression levels of both EGFR and ERCC1 was significantly associated with progression‐free survival. The mRNA levels of EGFR had a significant correlation with expression levels of ERCC1, GST‐P1 and VEGF. This small retrospective study suggests that gene expression levels of EGFR, ERCC1 and GST‐P1 may be useful in predicting the clinical outcome of patients with metastatic CRC treated with first‐line CPT‐11 based chemotherapy. © 2006 Wiley‐Liss, Inc.

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Vascular endothelial growth factor, CD68, and epidermal growth factor receptor expression and survival in patients with Stage II and Stage III colon carcinoma

Cited by 143 publications

References 36 publications

Protein Expression of STAT3, pSTAT3, MMP-7 and VEGF in Colorectal Adenocarcinoma: An Immunohistochemical Study

Protein Expression of STAT3, pSTAT3, MMP-7 and VEGF in Colorectal Adenocarcinoma: An Immunohistochemical Study

Stromal CCR6 drives tumor growth in a murine transplantable colon cancer through recruitment of tumor-promoting macrophages

Molecular determinants of irinotecan efficacy

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