The methylation status of the epidermal growth factor receptor (EGFR) gene was compared in cell lines from four major types of lung carcinoma, small cell lung carcinoma (SCLC), large cell lung carcinoma, squamous cell carcinoma and adenocarcinoma, in order to examine whether DNA methylation is responsible for the suppression of EGFR gene in SCLC cells.
Further, the human c-erb B-1/EGF-r gene in adenocarcinoma of uterine endometrium may be activated by a similar mechanism as that in the chicken v-erb B oncogene.
In cervical adenocarcinomas, expression of c-myc was seen in 5 of 7 cases (71.6%), EGFR in all cases and c-erbB-2 in 2 of 7 cases (28.6%). c-myc immunoactivity was observed as nuclear or cytoplasmic stain or both, EGFR as membrane and cytoplasmic stain, c-erbB-2 as membrane stain.
We examined prostatic adenocarcinomas from 19 formalin fixed radical prostatectomy specimens for EGFR by in situ hybridization employing a 24 base synthetic biotin-labeled oligonucleotide probe complementary to the 5' end of EGFR mRNA.
Down-modulation of epidermal growth factor receptor accompanies TNF-induced differentiation of the DiFi human adenocarcinoma cell line toward a goblet-like phenotype.
Because the prostate and breast cancer lines usually present autocrine stimulatory loops involving EGFR, we also examined transgenic adenocarcinoma mouse prostate C1 and MDA-468 treated with the EGFR-specific kinase inhibitor PD153035 to determine whether invasiveness is dependent on EGFR signaling.
The results indicate that EGFR autocrine loop activity in adenocarcinoma may have alternative signaling activities aside from the activation of ras-MAP kinase pathway.
Epidermal growth factor receptor overexpression is pronounced in virtually all squamous carcinomas and is also found in > or = 65% of large cell and adenocarcinomas.
In invasive tumors, EGFR are expressed in 50-90%, and mostly in squamous cell carcinomas, but also in adenocarcinomas and large cell carcinomas, while HER2 is less frequently expressed (20-30%) and mostly expressed in adenocarcinomas.
Patients with adenocarcinoma with cytoplasmic EGFr overexpression showed shorter overall survival than those with adenocarcinoma without cytoplasmic EGFr overexpression (P = 0.02).
Collectively, these data show that adenocarcinomas from never smokers comprise a distinct subset of lung cancers, frequently containing mutations within the TK domain of EGFR that are associated with gefitinib and erlotinib sensitivity.
We conclude that gastric adenocarcinomas potentially dependent upon the TGFalpha-EGFR autocrine loop for growing exhibit increased aggressiveness in the presence of aberrant p53.
The tight association with adenocarcinoma and the high frequency of mutations raise the possibility that EGFR mutations play an important role in the tumorigenesis of adenocarcinoma of lung, especially in East Asians.
With the use of PCR and direct DNA sequencing, EGFR mutations identical to the tumors were detected in the normal respiratory epithelium in 9 of 21 (43%) patients with EGFR mutant adenocarcinomas but none in patients without mutation in the tumors.
We have identified subpopulations of an adenocarcinoma cell line that are naturally resistant to gefitinib, and have analysed the cDNA expression profiles, genomic status of EGFR gene and the effect of gefitinib on signalling pathways in these cell lines in order to identify key mechanisms for naturally acquired resistance to gefitinib.