Overexpression of p185 is not related to erbB2 amplification in ovarian cancer.
BACKGROUND
While in breast cancer the amplification and overexpression of the erbB2 gene has been reported in numerous studies and found to be correlated to poor prognosis, information about this oncogene with respect to ovarian cancer is still limited. A recent study reported that approximately 30% of tumor biopsies from ovarian cancer patients exhibited erbB2 amplification and overexpression and suggested that the overexpression of this oncogene is an indicator of bad prognosis in ovarian cancer. The purpose of our studies was to investigate amplification of the erbB2 gene, the levels of erbB2 m-RNA and the erbB2 product (p185) in ovarian cancer, and the correlation between these findings and the pathological and clinical features.


RESULTS
Amplification of the erbB2 gene was investigated by Southern blot analysis in 75 samples from 62 patients; mRNA levels were evaluated by Northern blot analysis in 58 samples from 48 patients; and p185 was determined by immunohistochemistry in 65 samples from 65 patients. The erbB2 gene was amplified in only one case (1.6%), and a marked increase in erbB2 mRNA was found only in the same case. Staining for p185 was positive in 12 cases (18.5%). The staining was always confined to the cytoplasm except in the case that showed amplification of erbB2 in which p185 was localized in the membrane. No correlation was found between p185 positivity and pathological and clinical features or response to chemotherapy. Western blot analysis showed that the molecular weight of p185 in positive ovarian cancer cells was approximately 10 KDa lower than in breast cancer.


CONCLUSIONS
In contrast to breast cancer, in ovarian cancer the amplification of erbB2 appears infrequent. The levels of p185 detected by immunohistochemistry were not related to the amplification of the gene or to the increase in mRNA, suggesting the possibility of a longer half-life of the protein in the positive cases. The finding that erbB2 product in ovarian cancer is mostly localised in cytoplasm and not in the membrane as in breast cancer and that it has a lower molecular weight than the p185 in breast cancer suggest that this oncogene plays a different biological role in these two neoplasms.
Morali
F
F
Istituto di Ricerche Farmacologiche Mario Negri Milan, Italy.
Cattabeni
M
M
Tagliabue
E
E
Campiglio
M
M
Menard
S
S
Marzola
M
M
Lucchini
V
V
Colombo
N
N
Mangioni
C
C
Redaelli
L
L
D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D005786:Gene Expression Regulation; D006801:Humans; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases
D066246:ErbB Receptors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases