EGFR and gastrointestinal stromal tumor: an immunohistochemical and FISH study of 82 cases

Abstract

Gastrointestinal stromal tumor is the most common mesenchymal neoplasm of the gastrointestinal tract. Mutually exclusive KIT or platelet-derived growth factor receptor-a mutations are key events in gastrointestinal stromal tumor pathogenesis, and specific treatment targeting KIT/platelet-derived growth factor receptor-a activation is available. Epidermal growth factor receptor plays an important role in cancer biology and also constitutes a promising molecular target of therapy. Very few reports have been published in the literature about the relationship between gastrointestinal stromal tumor and epidermal growth factor receptor. The aim of this study was to investigate epidermal growth factor receptor immunohistochemical expression and epidermal growth factor receptor gene amplification in 82 consecutive gastrointestinal stromal tumor cases using tissue microarray technique. Hematoxylin-and eosin-stained sections and clinical information were reviewed, and expression of CD117 (KIT), CD34 and epidermal growth factor receptor was investigated by immunohistochemistry. Epidermal growth factor receptor gene copy number was determined using fluorescence in situ hybridization. Immunohistochemistry revealed that CD117 and CD34 were expressed in 96 and 57% of tumors, respectively. Variable epidermal growth factor receptor protein immunohistochemical overexpression was detected in 96% of gastrointestinal stromal tumor cases, but none of the 75 cases with represented tumor tissue cores and countable fluorescence signals exhibited epidermal growth factor receptor gene amplification by fluorescence in situ hybridization. These results show that there is no correlation between epidermal growth factor receptor protein overexpression by immunohistochemistry and epidermal growth factor receptor gene amplification by fluorescence in situ hybridization. Considering that the mechanisms of epidermal growth factor receptor protein overexpression are not well understood and the possibility that anti-epidermal growth factor receptor therapy may be beneficial for patients with gastrointestinal stromal tumor that overexpresses epidermal growth factor receptor, additional studies are encouraged. Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal (GI) tract. GIST generally occurs in older individuals (over the age of 50) and it can arise anywhere along the GI tract or even outside of it (extra-GI GIST), as in mesentery, omentum, retroperitoneum and pelvis. GISTs show peculiar immunohistochemical (KIT or CD117 and CD34 positivity) and molecular genetic findings, the latter characterized by mutually exclusive KIT or plateletderived growth factor receptor-a (PDGFRA) mutations. 1,2 The KIT and PDGFRA genes encode for similarly named transmembrane tyrosine kinase receptors that are involved in the development and maintenance of several cells. Activating (gain-offunction) mutations of KIT or PDGFRA permit the phosphorylation of the receptor tyrosine kinases, with activation of intracellular do...

An overview of the epidermal growth factor receptor fluorescence in situ hybridisation challenge in tumour pathology

“…EGFR FISH studies have shown that gene amplification is a rare event in BC,62 – 65 pancreatic carcinoma (PaC),66 67 ovarian carcinoma (OC),68 69 hepatocellular carcinoma (HCC),70 71 squamous cell carcinoma of the anal canal (SCAC),72 small cell carcinoma of urinary bladder (SCCUB),73 and gastrointestinal stromal tumours (GIST) 74 75. Moreover, EGFR gene amplification is infrequent in gastric cancer (GC),76 – 79 prostate cancer (PrC),80 – 82 and soft tissue sarcomas (STS)8 (see table 5 for details).…”

“…In most papers, EGFR gene amplification was defined using the classical and well accepted gene/centromere ratio, or using as a cut-off the presence of >4 EGFR gene signals per nucleus, or both criteria 8 62 – 66 70 – 75 80 – 82…”

Determinación inmunohistoquímica y utilidad pronóstica del receptor del factor de crecimiento epidérmico en los tumores estromales gastrointestinales

“…El porcentaje de inmunotinción se redujo a 84,45%, al incluir en un nuevo estudio a un mayor volumen poblacional (9). Las conclusiones sobre el mecanismo de expresión de EGFR en GIST y su valor pronóstico no quedaron demostrados, destacando que en aquellos enfermos que expresen inmunohistoquímica-mente EGFR, podría ser de importancia la posibilidad de tratamiento anti-EGFR (8)(9)(10)(11)(12).…”

Up‐regulated expression of ADAM17 in gastrointestinal stromal tumors: coexpression with EGFR and EGFR ligands

“…Recently, Cai et al and Lopes and Bacchi also reported immunohistochemical expression of EGFR in 33% and 96% of GIST, respectively. (26,27) The activation of EGFR is essential for carcinogenesis and metastasis in many cancers, and EGFR is amplified and/or over-expressed in human glioblastomas, malignant melanomas, epidermoid carcinomas, and gastrointestinal, urinary, and reproductive tract malignancies. (25,28) Moreover, it was shown that EGFR signal transactivation occurs via metalloproteinase-mediated processing of EGFR ligand precursors.…”