Nuclear expression of phosphorylated EGFR is associated with poor prognosis of patients with esophageal squamous cell carcinoma.
OBJECTIVE
Although it has been reported that epidermal growth factor receptor (EGFR) is able to translocate from the plasma membrane to the nucleus, the pathophysiological role of this translocation in tumorigenicity is still unclear. In the present study, to elucidate the pathophysiological significance of EGFR translocation, we investigated the expression not only of conventional EGFR but also its phosphorylated form (pEGFR), focusing on its cellular localization in esophageal cancer tissues.


METHODS
Fifty-two specimens of esophageal squamous cell carcinoma (SCC) obtained by surgery were examined immunohistochemically for their EGFR and pEGFR immunostaining patterns. The relationships between clinicopathological parameters and EGFR or pEGFR immunostaining patterns were then analyzed.


RESULTS
In 37 (71.2%) of the 52 esophageal SCCs, EGFR immunoreactivity was clearly localized at the plasma membrane of the cancer cells, whereas pEGFR immunoreactivity was clearly localized in the nucleus in 19 (36.5%) cases. Nuclear expression of pEGFR significantly correlated with TNM stage and lymph node metastasis, and moreover was associated with a poor outcome of esophageal SCC.


CONCLUSIONS
Nuclear translocalization of pEGFR is associated with an increase in the malignant potential of esophageal SCC and may affect prognosis in patients with esophageal SCC.
Hoshino
Mina
M
Department of Surgical and Molecular Pathology, Dokkyo University School of Medicine, Tochigi, Japan.
Fukui
Hirokazu
H
Ono
Yuko
Y
Sekikawa
Akira
A
Ichikawa
Kazuhito
K
Tomita
Shigeki
S
Imai
Yasuo
Y
Imura
Johji
J
Hiraishi
Hideyuki
H
Fujimori
Takahiro
T
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002462:Cell Membrane; D002467:Cell Nucleus / Q000378:metabolism*; D066246:ErbB Receptors / Q000096:biosynthesis*; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D010766:Phosphorylation; D011379:Prognosis; D021381:Protein Transport / Q000502:physiology
D014408:Biomarkers, Tumor; D066246:ErbB Receptors