Overexpression and relationships of HER-2/neu, epidermal growth factor receptor, p53, Ki-67, and tumor necrosis factor alpha in epithelial ovarian cancer.
OBJECTIVE
To determine the frequency and possible relationships of overexpression of oncogenes, cytokines, and cellular proliferation proteins in ovarian cancer.


METHODS
Sixty-four epithelial ovarian cancer specimens were obtained from the GOG tumor bank. Using immunocytochemistry, tumors were stained for overexpression of HER-2/neu, epidermal growth factor receptor (EGFR), p53, tumor necrosis factor alpha (TNF alpha), and Ki-67 (a marker of cellular proliferation).


RESULTS
Twenty-one tumors were Stage I/II and 43 were Stage III/IV. HER-2/neu was overexpressed in 7 cases (11%), EGFR in 12 cases (19%), and p53 in 32 cases (50%). Ki-67 was expressed in all but one case, and high indices (expression in over 50% of cells) were seen in 18 cases (28%). TNF alpha was expressed in all but one case. Comparison between Stage I/II and Stage III/IV cases revealed no difference in the expression of these oncoproteins. Comparison by histologic grade also revealed no difference in the expression of the oncoproteins, except for EGFR, which was overexpressed only in Grade 3 tumors (p = 0.01). Comparison between tumors that did or did not overexpress p53 revealed insignificant differences in the expression of HER-2/neu, EGFR and TNF alpha. In addition there were no differences with respect to stage, grade, or histology when tumors where analyzed with respect to p53 overexpression. There was a trend towards an association between p53 overexpression and high levels of Ki-67 (p = 0.10). Comparison of tumors with high Ki-67 indices to those with lower indices also revealed no association with the expression of HER-2/neu, or EGFR, and there were no differences in stage or grade distribution.


CONCLUSIONS
Ki-67 and p53 were frequently overexpressed in this representative sample of ovarian cancers from the GOG tumor bank; however, their expression was not associated with stage, grade, histology, or overexpression of other oncoproteins. Lack of a recognizable pattern of oncogene overexpression emphasizes the underlying biologic complexity of ovarian cancer.
Goff
B A
BA
Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, USA.
Shy
K
K
Greer
B E
BE
Muntz
H G
HG
Skelly
M
M
Gown
A M
AM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D046508:Culture Techniques; D066246:ErbB Receptors / Q000032:analysis*; D005260:Female; D016158:Genes, p53 / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis*; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000473:pathology* / Q000503:physiopathology; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D066246:ErbB Receptors; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D014409:Tumor Necrosis Factor-alpha