Is EGFR a moving target during radiotherapy of carcinoma of the uterine cervix?
BACKGROUND
The epidermal growth factor receptor (EGFR) is frequently overexpressed in uterine cervix carcinoma. The role of the pre-treatment EGFR expression levels and the changes of expression induced by ionizing radiation (IR) have not been conclusively defined.


METHODS
The staining intensity (SI) and labeling index (LI) of EGFR were determined in 38 patients by immunohistochemistry (IHC). Biopsies were taken before after 1 week of RT. EGFR expression was correlated with cell cycle, apoptosis and angiogenesis.


RESULTS
Before RT, 87% and after 1 week of RT, 95% of samples were positive for EGFR (p=0.2). Two patterns were observed, either increasing or decreasing expression after initiating RT. An increase of the EGFR SI was seen in 63% of patients from a mean of 57 SI (SD+/-60) before RT to 142 SI (SD+/-80.8) (p=0.001) during RT. In 32% of cases, EGFR decreased from 165 SI before (SD+/-83.0) to 75 SI (SD+/-73.0) (p< or =0.001) during RT. Two of five (5%) patients negative for EGFR before RT remained negative. An increase of the RT-induced EGFR LI was associated with reduced microvessel density (MVD) (p=0.02). Changes of the EGFR LI did neither correlate with cell cycle arrest nor apoptosis.


CONCLUSIONS
EGFR expression changes unpredictably during RT. The implications of changing EGFR during RT remain to defined. Repeated biopsies and EGFR reassessment during RT may help to better define EGFR-targeted treatment.
Cerciello
Ferdinando
F
Radiation Oncology, Zurich University Hospital, Zürich, Switzerland.
Riesterer
Oliver
O
Sherweif
Mohamed
M
Odermatt
Bernhard
B
Ciernik
I Frank
IF
D000328:Adult; D017209:Apoptosis / Q000502:physiology; D016203:CDC2 Protein Kinase / Q000096:biosynthesis; D002453:Cell Cycle / Q000502:physiology; D019926:Cyclin B / Q000096:biosynthesis; D056744:Cyclin B1; D066246:ErbB Receptors / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology / Q000532:radiotherapy*
C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D066246:ErbB Receptors; D016203:CDC2 Protein Kinase