Cell-free 27 kDa heat shock protein (hsp27) and hsp27-cytochrome c complexes in the cervix of women with ovarian or endometrial cancer.
Antibodies to the 27 kDa heat shock protein (hsp27) are present in some women with ovarian and endometrial cancers but not in women with nonmalignant conditions or healthy women. The appearance of these antibodies suggests that the corresponding protein (hsp27) may be present in an extracellular form in gynecologic cancer patients. Synthesis of hsp27 is upregulated in gynecologic cancers and inhibits induction of apoptosis. We now report the detection of hsp27 as well as hsp27-cytochrome c complexes in cell-free endocervical or posterior vaginal specimens from women with endometrial or ovarian cancer. Specimens were obtained with a cotton swab from 209 consecutive patients seen by a gynecologic oncologist. After removal of cellular components, aliquots of supernatants were assayed by ELISA for hsp27, using cytochrome c bound to microtiter plate wells, and for hsp27-cytochrome c complexes, using antibodies to cytochrome c and hsp27. Among 47 women with ovarian cancer, 38.3% were positive for hsp27 and 27.7% had hsp27-cytochrome c complexes. Similarly, among 52 women with endometrial cancer, 34.6% were hsp27-positive and 30.8% had hsp27-cytochrome c complexes. In contrast to the women with ovarian or endometrial cancer, of the 86 women with benign diagnoses only, 10.5% had cervical hsp27 (p < 0.002) and 8.1% had hsp27-cytochrome c complexes (p < 0.004). Among ovarian cancer patients, hsp27 was identified in 44.0% of the 25 women with active disease as opposed to 17.6% of the 17 patients in remission (p < 0.05). In women with stage 1-2 active ovarian cancer, 8 of 10 (80.0%) were hsp27-positive as opposed to 3 of 14 (21.4%) stage 3-4 patients (p < 0.01). For hsp27-cytochrome c complexes, 50% of ovarian cancer patients with active stage 1-2 disease as opposed to 21.4% with stage 3-4 disease were positive. Among women with endometrial cancer, only 10 of the 52 patients had active disease and 44 were in stage 1-2. For this malignancy, there was no relation between detection of hsp27 or hsp27-cytochrome c and active disease or cancer stage. Our results suggest that cell-free hsp27 and hsp27-cytochrome c complexes can be detected in the lower genital tract of women with ovarian and endometrial cancers. Identification of these biomarkers may be beneficial in the early diagnosis of these malignancies.
Korneeva
Irina
I
Department of Obstetrics and Gynecology, Weill Medical College of Cornell University, New York, New York, USA.
Caputo
Thomas A
TA
Witkin
Steven S
SS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002474:Cell-Free System; D003574:Cytochrome c Group / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000378:metabolism*; D005260:Female; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D006801:Humans; D046911:Macromolecular Substances; D008875:Middle Aged; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism*
D003574:Cytochrome c Group; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D046911:Macromolecular Substances; D018832:Molecular Chaperones; D009363:Neoplasm Proteins