BAX protein expression and clinical outcome in epithelial ovarian cancer.
OBJECTIVE
Expression of the pro-apoptotic protein BAX sensitizes ovarian cancer cell lines to paclitaxel in vitro by enhancing the pathway of programmed cell death. The present study was performed to determine the relationship between BAX expression and clinical outcome in 45 patients with newly diagnosed ovarian cancer.


METHODS
BAX protein expression was analyzed by immunohistochemistry, and its relationship with clinical outcome was determined. Assessment of BAX mRNA transcript levels and mutational analysis of the BAX coding region were also performed.


RESULTS
BAX protein was expressed at high levels (defined as > or = 50% of tumor cells positive) in tumor tissue from 60% of newly diagnosed patients. All patients whose tumors expressed high levels of BAX achieved a complete response (CR) to first-line chemotherapy that contained paclitaxel plus a platinum analogue, compared with 57% of patients in the low-BAX group (P = .036). After a median follow-up of 1.9 years, the median disease-free survival (DFS) of patients in the high-BAX group has not been reached, compared with a median DFS of 1.1 years for low-BAX expressors (P = .0061). BAX retained independent prognostic significance in multivariate analysis when corrected for stage and histology. BAX mRNA transcripts were easily detected in samples with low BAX protein expression, and no BAX mutations were identified.


CONCLUSIONS
The correlation between high BAX levels and improved clinical outcome suggests that an intact apoptotic pathway is an important determinant of chemoresponsiveness in ovarian cancer patients who receive paclitaxel.
Department of Adult Oncology, Dana-Farber Cancer Institute, Beth Israel Hospital, Harvard Medical School, Boston, MA 02115, USA.
Y T
YT
Tai
S
S
Lee
E
E
Niloff
C
C
Weisman
T
T
Strobel
S A
SA
Cannistra
D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002277:Carcinoma / Q000737:chemistry / Q000473:pathology*; D018076:DNA, Complementary / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology*; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis; D017422:Sequence Analysis, DNA; D051028:bcl-2-Associated X Protein
D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; D018076:DNA, Complementary; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D017239:Paclitaxel