HER-3 in colorectal tumourigenesis: from mRNA levels through protein status to clinicopathologic relationships.
BACKGROUND
Colorectal cancer is a major cause of cancer mortality in the Western world. Although HER-3 signalling is known to be implicated in colorectal carcinogenesis, the significance of its expression, localisation and phosphorylation remains elusive.


METHODS
Quantitative RT-PCR for HER-3 mRNA and immunohistochemistry for HER-3 and phosphorylated HER-3 (pHER-3) protein were performed in normal tissue, adenomas and carcinomas from 140 patients with colorectal cancer.


RESULTS
HER-3 was detected both in the cytoplasm and nucleus, whereas pHER-3 was observed in the nucleus and membrane of cells. A possible switch in HER-3 topography from the nucleus to the cytoplasm during colorectal tumourigenesis is suggested. The expression of pHER-3 did not differ significantly in normal tissue, adenomas and carcinomas, but was related to disease stage. HER-3 mRNA overexpression was significantly associated with decreased time to disease progression. It was also correlated with higher median age, left colon and rectal tumour sites and lymph node involvement.


CONCLUSIONS
We postulate that HER-3 is critically involved in colorectal tumourigenesis and its expression/phosphorylation might be of prognostic significance.
Grivas
Petros D
PD
Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece.
Antonacopoulou
Anna
A
Tzelepi
Vassiliki
V
Sotiropoulou-Bonikou
Georgia
G
Kefalopoulou
Zinovia
Z
Papavassiliou
Athanasios G
AG
Kalofonos
Haralabos
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002467:Cell Nucleus / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality; D003593:Cytoplasm / Q000378:metabolism; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D009363:Neoplasm Proteins; D012333:RNA, Messenger; D020893:Receptor, ErbB-3