IGF-IR in patients with advanced colorectal cancer in correlation with certain clinico-morphological factors: Initial report

Kukliński, Adam; Kamocki, Zbigniew; Koda, Mariusz; Piotrowski, Z; Sulkowski, Stanisław; Leśniewicz, R; Pawlak, Krystyna; Myśliwiec, Piotr; Kędra, Bogusław

doi:10.3892/ol.2011.396

Cited by 12 publications

(8 citation statements)

References 23 publications

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“…Our study is not unique in finding lower expression levels at advanced tumor stages: in breast and colorectal cancer this phenomenon has also been described [19,26,27]. Also, the decrease in expression might be due to the dedifferentiation process to which cancer cells are exposed; by becoming more invasive the expression of the IGF-1R gets lost [27].…”

Section: Discussionsupporting

confidence: 69%

“…A pathologist specialized on GI pathology (KBI) scored the immunohistochemically stained slides, blinded from the clinical data. Thereby, the staining was scored as “absent or low expression” or “high expression.” “High expression” was defined as intense staining in at least 10% of the cells of interest (dysplastic or carcinoma cells), as used in an earlier study on IGF‐1R expression . Membranous or cytoplasmatic localization of the IGF‐1R was also scored.…”

Section: Methodsmentioning

confidence: 99%

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Absence or low IGF‐1R‐expression in esophageal adenocarcinoma is associated with tumor invasiveness and radicality of surgical resection

Bruijn

Biermann

Shapiro

et al. 2015

Journal of Surgical Oncology

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Section: Discussionsupporting

confidence: 69%

Section: Methodsmentioning

confidence: 99%

Absence or low IGF‐1R‐expression in esophageal adenocarcinoma is associated with tumor invasiveness and radicality of surgical resection

Bruijn

Biermann

Shapiro

et al. 2015

Journal of Surgical Oncology

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“…This finding is furthermore reflected in the lower levels of these IGF pathway proteins and their mRNAs in association with shorter 10-year disease-free survival and overall rates. A decrease in both IGF1R protein and gene expression levels has been described before in esophageal adenocarcinoma, colorectal and breast cancer (Schnarr et al 2000, Allison et al 2007, Kuklinski et al 2011, De Bruijn et al 2015 and might reflect a dedifferentiation process. Indeed, two recent genomic studies have identified distinctive m(i) RNA expression profiles, separating PanNET with liver metastases (metastasis like primary tumor subtype) from well-differentiated PanNETs (well-differentiated islet/insulinoma tumor subtype), further underscoring dedifferentiation to be reflected in gene expression signatures (Sadanandam et al 2015, Scarpa et al 2017.…”

Section: Discussionsupporting

confidence: 54%

The IGF pathway is activated in insulinomas but downregulated in metastatic disease

Henfling¹,

Perren²,

Schmitt³

et al. 2018

Endocrine-Related Cancer

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Clinical and molecular studies have implicated epidermal growth factor receptor (EGFR), insulin-like growth factor (IGF) and target of rapamycin (mTOR) signaling pathways in the regulation of pancreatic neuroendocrine tumor (PanNET) growth. Interpretation and comparison of these studies is complex due to clinical and molecular tumor heterogeneity. We therefore focused in this study on insulinomas, which we examined for mRNA and protein expression of EGFR, IGF and mTOR signaling pathway components by quantitative real-time PCR (n=48) and immunohistochemistry (n=86). Findings were compared with normal pancreatic islets and correlated with histopathological data and clinical outcome. Insulinomas showed low EGFR and high IGF2 expression. IGFBP2, IGFBP3 and IGFBP6 mRNA levels were 2-4 folds higher than in islets. High protein expression of IGF2, IGF1R and INSR (in 51-92% of the tumors) and low to moderate expression of mTORC1 pathway proteins p-PS6k and p-4EBP1 (7-28% of the tumors) were observed. Correlations were found between 1) ERK1 mRNA expression and that of numerous IGF pathway genes, 2) p-ERK and IGF1R protein expression and 3) decrease of IGF pathway components and both metastatic disease and shorter 10 years disease free survival. In conclusion, our observations suggest that high expression of IGF signaling pathway components is a hallmark of insulinomas, but does not necessarily lead to increased mTOR signaling. Reduced expression of IGF pathway components may be an adverse prognostic factor in insulinomas.

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“…At present, tissue sampling remains the gold standard in the assessment of tumour genetic features [17]. A fraction of CRC DNA is shed into the blood, and sensitive methods to detect it have now been introduced.…”

Section: Nucleic Acidsmentioning

confidence: 99%

Markers of metastatic colorectal cancer

Myśliwiec

Choromańska

Dadan

2020

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Metastatic colorectal cancer (CRC) is a major cause of cancer-related death. However, early diagnosis of CRC metastases offers a chance of long-term survival in as much as 40% of patients after curative treatment. Current guidelines are based on clinical examination, carcinoembryonic antigen (CEA) testing, computed tomography scanning, and endoscopic surveillance. Although CEA is the most widely used laboratory test, it has very low sensitivity (30-40%). Moreover, there is no evidence to support the association of CEA testing with improved survival or quality of life. Thus, novel markers with greater specificity and sensitivity are needed. The aim of this review was to define the role of available laboratory markers in early diagnosis of metastatic CRC. We identified novel tests with the highest association to metastatic CRC: circulating tumour DNA, growth/differentiation factor 15, and β6-integrin. We also discuss other promising markers, although most of the studies are preliminary and require validation.

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IGF-IR in patients with advanced colorectal cancer in correlation with certain clinico-morphological factors: Initial report

Cited by 12 publications

References 23 publications

Absence or low IGF‐1R‐expression in esophageal adenocarcinoma is associated with tumor invasiveness and radicality of surgical resection

Absence or low IGF‐1R‐expression in esophageal adenocarcinoma is associated with tumor invasiveness and radicality of surgical resection

The IGF pathway is activated in insulinomas but downregulated in metastatic disease

Markers of metastatic colorectal cancer

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