Expression of epidermal growth factor family proteins and epidermal growth factor receptor in human endometrium.
The biological significance of epidermal growth factor (EGF)-related proteins in the development and progression of endometrioid endometrial carcinoma was studied. Expression of EGF-related proteins including EGF, transforming growth factor-alpha (TGF-alpha), cripto (CR), amphiregulin (AR), and EGF receptor (EGFR) were immunohistochemically examined. Results were then correlated with clinicopathologic findings and steroid receptor status in 12 specimens with normal endometrium, 13 with endometrial hyperplasia, and 40 with endometrioid endometrial carcinoma. EGFR, EGF, TGF-alpha, and CR immunoreactivities were observed in 58.3%, 66.7%, 91.6%, and 66.7% of normal endometrial specimens; 100%, 15.4%, 100%, and 30.8% of endometrial hyperplasia specimens; and 67.5%, 32.5%, 65.0%, and 65.0% of endometrial carcinoma specimens, respectively. AR immunoreactivity was not observed in any of the normal, hyperplastic, or neoplastic endometrium. The presence or absence of EGFR or TGF-alpha in endometrial carcinoma correlated with surgical stage, depth of myometrial invasion, and findings from peritoneal washing cytology. EGF expression significantly correlated with the age of the patients and that of CR with surgical stage and peritoneal washing cytological findings. There was a significant correlation between EGFR and TGF-alpha expression, and between EGF and TGF-alpha. Co-expression of EGFR and TGF-alpha, EGFR and CR, and TGF-alpha and CR in carcinoma specimens significantly correlated with advanced surgical stage, deeper myometrial invasion, and positive peritoneal washing cytology. In normal as well as hyperplastic endometrium, endometrial glands immunohistochemically positive for TGF-alpha were generally positive for ER, but in poorly differentiated endometrial carcinoma, cells positive for TGF-alpha tended to be negative for ER. The results of the present study show that among EGF-related proteins, expression of TGF-alpha and CR seem to be associated with the progression of human endometrioid endometrial carcinoma. Additionally, expression of TGF-alpha became increasingly estrogen independent with increasing histological carcinoma grades.
Niikura
H
H
Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Sendai, Japan.
Sasano
H
H
Kaga
K
K
Sato
S
S
Yajima
A
A
D000328:Adult; D066258:Amphiregulin; D018269:Carcinoma, Endometrioid / Q000737:chemistry* / Q000473:pathology; D066255:EGF Family of Proteins; D004714:Endometrial Hyperplasia / Q000378:metabolism / Q000473:pathology; D016889:Endometrial Neoplasms / Q000737:chemistry* / Q000473:pathology; D004717:Endometrium / Q000737:chemistry*; D004815:Epidermal Growth Factor / Q000032:analysis*; D066246:ErbB Receptors / Q000032:analysis*; D005260:Female; D058851:GPI-Linked Proteins; D006023:Glycoproteins / Q000032:analysis; D006133:Growth Substances / Q000032:analysis*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D009367:Neoplasm Staging; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D011987:Receptors, Steroid / Q000096:biosynthesis; D012189:Retrospective Studies; D016211:Transforming Growth Factor alpha / Q000032:analysis
C587848:AREG protein, human; D066258:Amphiregulin; D066255:EGF Family of Proteins; D058851:GPI-Linked Proteins; D006023:Glycoproteins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011987:Receptors, Steroid; C070636:TDGF1 protein, human; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D066246:ErbB Receptors