Molecular mechanisms other than activating KRAS mutations should underlie the occurrence of weaker versus stronger responses to cetuximab (CTX) in EGFR-dependent carcinomas with either an intact KRAS signaling or in which KRAS mutations do not predict CTX efficacy.
Protein overexpression and gene amplification of epidermal growth factor receptor in nonsmall cell lung carcinomas. An immunohistochemical and fluorescence in situ hybridization study.
EGFR and KRAS mutational status can be determined in biopsies representing bronchial pulmonary carcinomas because when a mutation is present it is generally present in all the histological patterns.
We analysed 361 RCCs (334 clear-cell carcinomas) from a multi-centre case-control study for mutations in TP53 (exons 5-9 in the whole series and exons 4 and 10 in a pilot subset of 60 tumours) and a pilot 50 tumours for mutations in EGFR (exons 18-21) or KRAS (codon 12) in relation to VHL status.
Here we studied epidermal growth factor receptor (EGFR) and K-RAS oncogene, 2 biological markers closely associated with tumorigenesis and altered in many types of tumors, including lung carcinomas.
In addition to the mutational status of KRAS, the epidermal growth factor receptor (EGFR) ligands amphiregulin (AREG) and epiregulin (EREG) might function as bona fide biomarkers of cetuximab (Ctx) sensitivity for most EGFR-driven carcinomas.
The purpose of this study was to identify possible alterations in proto-oncogenes (c-fos, c-jun, c-erbB1, c-erbB2 and c-myc) at the protein level in primary lung carcinomas and simultaneous metastatic lymph nodes of 21 patients.
Single-dose administration of EMD 55900 was very well tolerated in all patients, and good (100 mg) to excellent (400 mg) homogeneous binding of mAb to EGF-R was obtained in the advanced laryngeal and hypopharyngeal carcinomas studied.
Eighty-three percent (19 of 23) had de novo SCLCs, whereas 17% had SCLC transformation as acquired resistance to erlotinib after treatment for EGFR-mutant lung carcinomas.
Twenty nine (50%) of 58 carcinomas were positive for EGF-R and c-erbB-2 product, 55 (94.8%) for c-myc product, 9 (15.5%) for c-H-ras product and 17 (29%) for TGF-alpha.
<b>Purpose:</b> This study investigated the safety, clinical activity, and target-associated biomarkers of lumretuzumab, a humanized, glycoengineered, anti-HER3 monoclonal antibody (mAb), in combination with the EGFR-blocking agents erlotinib or cetuximab in patients with advanced HER3-positive carcinomas.<b>Experimental Design:</b> The study included two parts: dose escalation and dose extension phases with lumretuzumab in combination with either cetuximab or erlotinib, respectively.
Southern blot hybridization experiments with DNAs from tumors demonstrated amplification of the epidermal growth factor receptor gene (c-erbB) in two of 25 carcinomas.
Significantly higher scores of cytoplasmic EGFR staining were found in carcinomas with gene amplification when the cell reaction was examined in the basal and suprabasal layer.
A tissue microarray of 66 salivary duct carcinomas was used for immunohistochemical analysis of HER-2 and EGFR expression (semiquantitatively evaluated into a three-tiered system), and fluorescence in situ hybridization for gene copy number, and chromosomes 7 and 17 ploidy status.
Polysomy 7 was commonly present in pure apocrine carcinomas (61 vs 27% of apocrine-like carcinomas; P=0.083) and showed a weak positive correlation with EGFR protein expression (P=0.025, r=0.326).
The chimeric anti- EGFR monoclonal antibody cetuximab has been approved for EGFR-expressing colorectal tumors in patients who progress after irinotecan-based chemotherapy in combination with irinotecan and in squamous cell head and neck carcinomas for patients with locally advanced disease in combination with radiation therapy or after failure of platinum-based chemotherapy in recurrent or metastatic disease (FDA).
The epidermal growth factor receptor (EGFR) is overexpressed in 50-70% of human primary breast, lung, and colon carcinomas, whereas it is not usually expressed in hematopoietic cells.