Epidermal growth factor receptor overexpression in esophageal carcinoma. An immunohistochemical study correlated with clinicopathologic findings and DNA amplification.
BACKGROUND
Many studies have reported the increased expression of epidermal growth factor receptor (EGFR) in various human malignancies and its association with the biologic behavior of the tumors.


METHODS
We performed an immunohistochemical analysis of the EGFR in 217 cases of human esophageal squamous cell carcinoma, 161 lymph node metastases and 23 foci of squamous dysplasias. The findings were correlated with clinicopathologic features, including the clinical outcome. Southern blot analysis was performed in 42 cases for the detection of DNA amplification of the EGFR gene and subsequently was correlated with EGFR immunoreactivity.


RESULTS
Epidermal growth factor receptor overexpression was detected in 71% of primary tumors and 88% of lymph node metastases, as compared to nonpathologic adjacent esophageal epithelium. Statistically significant correlations were observed between EGFR overexpression and sex, age, histologic type, and the presence of invasion. Tumor staining was classified into two patterns, homogeneous and heterogeneous, based on the distribution of EGFR-positive cells. The immunostaining patterns of primary tumors had a statistically significant correlation with histologic type, the presence of adventitial invasion, histologic stage and lymph node metastasis. There was a tendency toward a worse prognosis for those patients with EGFR overexpression in the primary tumor. Greater than 90% of the foci of squamous dysplasia demonstrated homogeneous EGFR overexpression. DNA amplification of the EGFR was observed in 21% of primary tumors, and all demonstrated immunohistochemical overexpression.


CONCLUSIONS
Immunohistochemical overexpression of the EGFR, which was more frequent than EGFR DNA amplification, appears to play an important role in biologic behavior of human esophageal squamous cell carcinomas.
Itakura
Y
Y
Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
Sasano
H
H
Shiga
C
C
Furukawa
Y
Y
Shiga
K
K
Mori
S
S
Nagura
H
H
D015139:Blotting, Southern; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000473:pathology*; D004247:DNA / Q000032:analysis; D015342:DNA Probes; D066246:ErbB Receptors / Q000032:analysis* / Q000235:genetics; D004938:Esophageal Neoplasms / Q000737:chemistry* / Q000473:pathology*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis
D015342:DNA Probes; D004247:DNA; D066246:ErbB Receptors