Immunophenotype of ovarian cancer as predictor of clinical outcome: evaluation at primary surgery and second-look procedure.
OBJECTIVE
This study was undertaken to evaluate whether immunophenotyping of advanced epithelial ovarian cancer could predict response to initial chemotherapy and whether tumor immunophenotype changed after chemotherapy.


METHODS
Fifty-four patients with stage III and IV ovarian cancer, treated at the University of Washington Medical Center, had pathology specimens evaluated. A subset of 23 patients also had specimens from a secondary surgery evaluated. Using immunocytochemistry, tumors were immunostained for overexpression of c-erb-B-2, epidermal growth factor receptor (EGFR), p53, and expression of the Ki67-defined antigen (a marker of cellular proliferation), tumor necrosis factor alpha (TNFalpha), estrogen receptor (ER), progesterone receptor (PR), and P-glycoprotein (P170, a marker of multidrug resistance). Twenty-four patients had a good response to chemotherapy (defined as a negative, or microscopically positive second look), and 30 had a poor response (defined as grossly positive second look or progressive disease).


RESULTS
Comparison of tumor markers from the initial and the secondary surgeries revealed that the only significant change was in the Ki67-defined cell proliferation rate, which showed a marked reduction in those with a good response to chemotherapy (P = 0.002). Comparison of tumor markers at initial surgery between good and poor responders revealed a correlation with p53 expression. Good responders were less likely to have p53 overexpression compared to poor responders, and this result approached significance (P = 0.058). Comparison of tumor markers at secondary surgery revealed a significant reduction in Ki67-defined cell proliferation rate in good responders compared to poor responders (P = 0.01). No significant differences were found between good and poor responders for the other tumor markers evaluated.


CONCLUSIONS
The only tumor markers to predict for response to chemotherapy were p53 at initial surgery (P = 0.058) and Ki67 indices at secondary surgery (P = 0.001). Expression of steroid hormone receptors, TNFalpha, and P-glycoprotein and overexpression of c-erb-B-2 or EGFR are not associated with chemoresistance.
Goff
B A
BA
Department of Obstetrics and Gynecology, University of Washington Medical Center, Seattle, Washington, 98195, USA.
Ries
J A
JA
Els
L P
LP
Coltrera
M D
MD
Gown
A M
AM
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012086:Reoperation; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53