PTEN status in advanced colorectal cancer treated with cetuximab.
BACKGROUND
Loss of phosphatase and tensin homologue deleted in chromosome 10 (PTEN) function in advanced colorectal cancer (CRC) may represent one of the resistance mechanisms to cetuximab by interfering with the epidermal growth factor receptor signal transduction pathway.


METHODS
PTEN expression tested by indirect immunofluorescence was evaluated both on primary (n=43) and on metastatic (n=24) sites in CRC patients treated with cetuximab.


RESULTS
The loss of PTEN expression tested on metastatic sites was negatively associated with response (100% progressive disease (PD) in PTEN-negative cases vs 30% PD in PTEN-positive cases; P<0.05), PFS (0.8 vs 8.2 months; P<0.001) and OS (2.9 vs 14.2 months; P<0.001).


CONCLUSIONS
A potential role of PTEN in the anti-tumour activity of cetuximab could be hypothesised.
Negri
F V
FV
Medical Oncology Unit, University Hospital, Parma 43100, Italy. francescanegri2@hotmail.com
Bozzetti
C
C
Lagrasta
C A
CA
Crafa
P
P
Bonasoni
M P
MP
Camisa
R
R
Pedrazzi
G
G
Ardizzoni
A
A
D000230:Adenocarcinoma / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000556:secondary; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000502:physiology; D005500:Follow-Up Studies; D017353:Gene Deletion; D018628:Gene Dosage; D020869:Gene Expression Profiling; D006801:Humans; D000077146:Irinotecan; D009363:Neoplasm Proteins / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000502:physiology; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D051059:PTEN Phosphohydrolase / Q000032:analysis* / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D016879:Salvage Therapy; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009363:Neoplasm Proteins; D009944:Organoplatinum Compounds; D047428:Protein Kinase Inhibitors; D000077150:Oxaliplatin; D000077146:Irinotecan; D019869:Phosphatidylinositol 3-Kinases; C512478:EGFR protein, human; D066246:ErbB Receptors; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D000068818:Cetuximab; D002166:Camptothecin