Coexpression of the HER-2 gene product, p185HER-2, and epidermal growth factor receptor, p170EGF-R, on epithelial ovarian cancers and normal tissues.
Monoclonal antibodies (MAbs) and immunoconjugates reactive with different antigens expressed by neoplastic cells can inhibit tumor growth. Use of these agents in combination with one another or with chemotherapy can exert additive or synergistic cytotoxicity against tumor cells. An augmented therapeutic activity with favorable therapeutic index might be attained when coexpression is observed on tumor cells, but not in normal tissues. In this study frozen sections of 19 ovarian cancers (2 stage I, 10 stage III, 2 stage IV, and 5 recurrent), as well as 29 normal tissues, were evaluated by immunohistochemistry using 11 distinct MAbs against HER-2/p185 and 2 antibodies against EGF-R/p170 to assess coexpression of these receptors. HER-2/p185 expression was detected in 5 to 100% of ovarian cancers and 0 to 50% of normal ovarian epithelia, depending on the antibody used. EGF-R/p170 expression was detected in approximately 70% of cancers and 40% of normal ovaries by both antibodies. Coexpression of p185 and p170 was observed in 47-68% of ovarian cancers and 9-18% of normal ovarian epithelial specimens depending upon the combination of antibodies used. Staining of 273 specimens from 29 normal tissues indicated that coexpression of HER-2 and EGF-R is rare. Normal tissues that coexpressed both receptors in > or =50% of the cases included cervix, endometrium, esophagus, skin, and prostate. These data confirm that HER-2 and EGF-R are more frequently expressed in advanced ovarian cancers than in normal ovarian epithelium and a significant fraction of these tumors coexpress both HER-2 and EGF-R.
Bast
R C
RC
Division of Medicine, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Pusztai
L
L
Kerns
B J
BJ
MacDonald
J A
JA
Jordan
P
P
Daly
L
L
Boyer
C M
CM
Mendelsohn
J
J
Berchuck
A
A
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D066246:ErbB Receptors / Q000302:isolation & purification*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009375:Neoplasms, Glandular and Epithelial / Q000737:chemistry*; D010051:Ovarian Neoplasms / Q000737:chemistry*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000302:isolation & purification*; D012867:Skin / Q000737:chemistry; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases