Lee Daly

Expression and amplification of the HER-2/ neu (c-erbB-2) protooncogene in epithelial ovarian tumors and cell lines

Amplification of the c-erbB-2 protooncogene has been associated with a poor prognosis in human breast and ovarian cancers. Our study was undertaken to examine whether amplification, rearrangement, or overexpression of c-erbB-2 and other protooncogenes was frequently observed in epithelial ovarian cancers. c-erbB-2 was expressed in 87% of 22 ovarian cancers analyzed, but expression was significantly increased in only one of the 22 tumor specimens. In this case elevated c-erbB-2 expression was associated with dramatic amplification of the gene. In another tumor a 3.8 kb EcoRI fragment was found, in addition to the usual 4.4 and 6.0 kb fragments; this is consistent with a possible gene rearrangement or a restriction fragment length polymorphism. To place these results in perspective, expression of several other protooncogenes has been examined in ovarian carcinomas. The c-fos, c-myc, n-myc, c-fms, and c-Ha-ras protooncogenes were expressed in different fractions of tumors, but expression of l-myc, c-erbB, c-myb, c-sis, and c-mos was not detectable. Aside from c-erbB-2, neither amplification nor rearrangement was observed among the other protooncogenes studied. Expression of c-erbB-2, c-fms, c-myc, n-myc, c-fos, and c-Ha-ras deserves further evaluation as a prognostic factor in ovarian cancer.

OVX1 radioimmunoassay complements CA-125 for predicting the presence of residual ovarian carcinoma at second-look surgical surveillance procedures

PURPOSE At second-look surgical surveillance procedures, normal CA-125 levels can be associated with persistent disease in 50% to 60% of patients. A novel radioimmunoassay (RIA) has been evaluated for the ability to identify patients with persistent disease who have normal levels of CA-125. MATERIALS AND METHODS The OVX1 double-determinant assay used a murine monoclonal antibody to detect an epitope on a high-molecular weight mucin-like glycoprotein. RESULTS Apparently healthy individuals had serum OVX1 levels of 2.23 +/- 2.48 U/mL (mean +/- SD). Elevated serum OVX1 levels (> 7.2 U/mL) were found in 5% of 184 normal individuals and in 70% of 93 epithelial ovarian cancer patients with clinically evident disease. Among sera from these ovarian cancer patients, OVX1 was elevated in 68% of 76 samples with CA-125 levels more than 35 U/mL and in 76% of 17 samples with CA-125 levels less than 35 U/mL. In serum samples obtained at the time of positive second-look laparotomy, 59% of 41 patients with CA-125 levels less than 35 U/mL had elevated OVX1 antigen levels, whereas 41% of 22 patients with CA-125 levels more than 35 U/mL had elevated serum OVX1 levels. In patients with negative second-look laparotomies, false-positive results were eliminated by increasing the threshold of OVX1 to 10.5 U/mL. At this level, 32% of 41 patients with positive second-look operations had an elevated OVX1 level, despite a normal CA-125 level. When used in combination, CA-125 (> 35 U/mL) and OVX1 (> 10.5 U/mL) detected persistent disease in 56% of 63 patients with positive surveillance procedures, compared with 35% when CA-125 was used alone (P < .05). CONCLUSION An elevated OVX1 level can alert oncologists to the possibility that ovarian cancer has persisted, despite the return of CA-125 to a normal range.

The prognostic significance of CA 125 half-life in patients with ovarian cancer who have received primary chemotherapy after surgical cytoreduction

Fifty-four patients with advanced epithelial ovarian cancer were monitored with serial serum CA 125 levels after surgical cytoreduction and during multi-agent chemotherapy with cisplatin-containing regimens. CA 125 half-life of less than 20 days was associated with prolonged overall survival (p less than 0.015). In those patients who eventually were found to be disease-free at surgical surveillance procedures, normalization of serum CA 125 levels to less than 35 U/ml within 65 days of primary operation also suggested an improved survival (p less than 0.059).

Comparison of a novel assay for breast cancer mucin to CA15-3 and carcinoembryonic antigen.

PURPOSE To compare the sensitivity and specificity of an automated microparticle enzyme immunoassay (MEIA) for breast cancer mucin (IMx BCM; Abbott Laboratories, North Chicago, IL) to that of CA15-3 and carcinoembryonic antigen (CEA) for detecting and monitoring breast cancer. MATERIALS AND METHODS IMxBCM was compared to assays of CA15-3 and CEA in 630 serum specimens from healthy women, and from women with breast cancer, other malignancies, benign breast conditions, or other benign diseases. RESULTS Analysis of the log-transforms for the three markers in all specimens showed a high correlation of IMxBCM with CA15-3 (r = .78), but not with CEA (r = .25). Based on a receiver-operating-characteristics (ROC)-curve analysis for any given specificity, IMxBCM was found to be a more sensitive marker than either CA15-3 or CEA for distinguishing 105 women with advanced or metastatic breast cancer from 89 healthy women (P = .003 and P = .04, respectively), from 98 women with benign breast conditions (P = .02 and P = .002), or from 191 women with benign diseases (P = .03 and P less than .0001). At 95% specificity, the sensitivities of IMxBCM, CA15-3, and CEA for detecting advanced or metastatic breast cancer were 69%, 51%, and 30%, respectively. Serial serum samples (n = 177) were analyzed in 20 additional metastatic breast cancer patients with measurable disease. Serial IMxBCM levels corresponded with the clinical course of disease in 80%, CA15-3 in 65%, and CEA in 60% of the 20 patients. CONCLUSIONS Increased sensitivity of IMxBCM, despite a high correlation with CA15-3, suggests that IMxBCM and CA15-3 may recognize distinct epitopes on the same molecule. Although further research is indicated, IMxBCM may provide a promising marker in the clinical management of breast cancer patients.

OVX1 and CEA in patients with colon carcinoma, colon polyps and benign colon disorders

The OVX1 tumor marker promises to complement CA125 for detection of early stage ovarian carcinoma. OVX1 has also been shown to be elevated in colon cancer patients. This study is designed to assess serum OVX1 levels in patients with specific stages of colon cancer, colon polyps or other GI disorders. Serum OVX1 and CEA were measured by radioimmunoassay or enzyme immunoassay for 206 patients at the time of colonoscopy or staging for colon carcinoma. In patients with stage I, II, III, or IV colon carcinoma, serum OVX1 was positive in 37%, 48%, 74% and 63%, respectively. Fifty-three percent of patients with colon polyps had elevated OVX1 levels, while OVX1 levels were positive in only 7% of healthy controls. If both OVX1 and CEA were considered, at least one of these markers was elevated in 36%, 60%, 79% or 89% of patients with stage I, II, III or IV colon carcinoma, respectively. The majority of patients with inflammatory bowel disease or diverticulosis also had elevated OVX1 levels. Both markers were positive in 27% of patients with colon carcinoma, and not in any patients with a normal colonoscopy or with a diagnosis of diverticulosis or hemorrhoids. In conclusion, serum OVX1 improves the sensitivity of CEA for detecting colon polyps and colon cancer; however, the use of OVX1 in this setting is hindered by its elevation in non-malignant colonic processes.

Ha-ras polymorphisms in epithelial ovarian cancer

Unusual restriction fragment length polymorphisms (RFLPs) of the Ha-ras locus have been found in DNA from leukocytes and tumor tissue of cancer patients. To determine whether rare alleles would be observed frequently in patients with ovarian cancer, Ha-ras RFLPs were studied in DNA from 42 different ovarian epithelial tumors and from the peripheral blood leukocytes of 76 normal individuals. Four common, seven intermediate, and seven rare alleles were detected overall. Similar fractions of rare alleles were found in DNA from ovarian cancers and from the peripheral blood of normal individuals. Thus, the frequency of unusual Ha-ras RFLPs did not distinguish patients with ovarian cancers from apparently healthy individuals.

Increased serum levels of macrophage colony‐stimulating factor in ovarian cancer

Macrophage colony-stimulating factor is a cytokine that stimulates proliferation and differentiation of phagocytic cells. Macrophage colony-stimulating factor is produced by ovarian epithelial cancer cell lines and might provide a useful serum marker for the disease. Among sera from 69 patients with clinically apparent epithelial ovarian cancer, 47 (68%) had at least 2.5 ng/ ml macrophage colony-stimulating factor, whereas only two of 80 apparently healthy donors (2.5%) had a comparable elevation of macrophage colony-stimulating factor. Circulating levels of macrophage colony-stimulating factor did not correlate with serum levels of CA 125. Moreover, 14 of 25 ovarian cancer patients (56%) with clinically evident disease and normal levels of CA 125 «35 U/ml) had elevated levels of macrophage colony-stimulating factor. Among 29 patients with serum CA 125 levels < 35 U/ml before positive surgical surveillance procedures, 9 (31%) had at least 2.5 ng / ml macrophage colony-stimulating factor. Elevated levels of macrophage colony-stimulating factor were also found in patients with carcinomas from other primary sites and in 31 % of 134 patients with benign diseases. If intercurrent benign disease can be taken into account, macrophage colony-stimulating factor deserves further evaluation in combination with CA 125 in monitoring ovarian cancer. (AM J OBSTET GVNECOL 1991;165:1356-62.)