Epitope recognition by anti-cathepsin D autoantibodies in endometrial cancer patients.

OBJECTIVE: This study analyzed a model for the identification of specific epitopes recognized by autologous tumor-reactive humoral responses of endometrial cancer patients as potential markers for the monitoring of cancer. METHODS: The presence of circulating pro- and mature forms of cathepsin D and antibodies reactive with this enzyme were identified by Western immunoblot and quantitated by an enzyme immunoassay. Specific immunoreactivities with 34- and 52-kDa cathepsin D forms were analyzed by Western immunoblot using sera from endometrial cancer patients (n = 40) and normal volunteers (n = 15). Subsequently, reactivities with specific cathepsin D epitopes were defined by a peptide-specific ELISA. RESULTS: Circulating pro-forms of cathepsin D were detected in 31 of 40 endometrial cancer patients tested and none of the control volunteers. Circulating IgG reactive with cathepsin D could be demonstrated in 29/31 patients with circulating procathepsin D, while an anti-cathepsin D response was not detectable in normal controls. This response appeared to be directed against the pro-peptide portion of cathepsin D. Using a peptide-specific ELISA, the frequencies of antibody production against specific epitopes within the pro-peptide were defined. CONCLUSION: There is a demonstrable tumor-reactive immune response elicited in endometrial cancer patients, directed against specific antigenic epitopes, some of which are conserved among these patients. Since these proteins are recognized as non-self, due at least in part to posttranslational processing errors, defining these epitopes will be useful as a means of diagnosis, assessment of therapeutic success, and, ultimately, identification of immunotherapeutic targets.

Murine intestinal crypt survival after combined taxol plus radiation exposure.

Taxol is active against a number of cancers, some of which are also radiosensitive. The role of combined Taxol and radiotherapy has not been established. A theoretical benefit exists, however, due to the G2/M phase specificity of Taxol, and radiation-sensitizing effects have been observed in vitro. This study focused on the combined Taxol/radiation effect on murine intestinal epithelium. HA/ICR random-bred male mice were used to examine the temporal effect of injecting Taxol (40 mg/kg) before and after irradiation (12.5 Gy). The microcolony assay was used to determine the effect of single and combined modalities. Control groups consisted of no treatment, drug solvent only (Cremophor/ethanol/saline), radiation only, and Taxol only. A complete radiation dose-response study of treatment with and without Taxol was performed 12 hr after injection. Preirradiation Taxol appears not to enhance intestinal cell killing, and may even offer some protection when injected at 4 hr prior to irradiation. Postirradiation Taxol was found to enhance radiation response most dramatically at times greater than 12 hr. Dose-response data appeared to confirm the increased radiation effect of combined treatment. In conclusion, Taxol administered prior to irradiation results in either no sensitization or possible protection of the normal tissue response. Postirradiation Taxol appears to sensitize intestinal crypts when injected at least 12 hr after gamma irradiation. These data suggest that care should be exercised when using Taxol after irradiation.

Vulvar eccrine porocarcinoma.

A rare case of a slowly growing vulvar tumor in a 75-year-old woman is presented. This vulvar neoplasm was an eccrine porocarcinoma with left inguinal nodal metastases. This is believed to be only the second reported case of a vulvar eccrine porocarcinoma. Treatment included a left hemivulvectomy, bilateral inguinal-femoral lymphadenectomy, and postoperative radiation therapy. A review of the literature regarding this unusual malignancy is included.

Late presentation of an alpha-fetoprotein secreting isolated large upper abdominal retroperitoneal Sertoli-Leydig cell tumor recurrence.

The following case reports the surgical and adjuvant treatment of a solitary upper abdominal retroperitoneal recurrence of a poorly differentiated Sertoli-Leydig cell tumor (SLCT) which presented 4 years after the original diagnosis. The patient was treated with en bloc resection of the mass, which included her left kidney, adrenal gland, and distal pancreas. She received four courses of adjuvant chemotherapy and remains without evidence of malignancy. Both the primary and recurrent tumor secreted alpha-fetoprotein allowing serologic follow-up. The utility of serum alpha-fetoprotein in disease response to treatment and for surveillance of recurrence is also shown.

Squamous cell carcinoma antigen: clinical utility in squamous cell carcinoma of the uterine cervix.

This study further defines the clinical utility of squamous cell carcinoma antigen (SCC-Ag) in initial squamous carcinoma of the cervix, response to treatment, and in the detection of recurrence. Serum specimens were drawn and analyzed from patients with squamous cell carcinoma. Charts were reviewed on 272 patients with 1053 samples evaluated. Treatment of patients prior to the availability of the assay and patients lost to follow-up resulted in lower total numbers of initial and recurrent values. Data were analyzed to detect trends during and after treatment. All values at or above the lowest detectable level of antigen were included; that is, 1.5 ng/ml and above. A SCC-Ag value > or = 2.0 ng/ml drawn at any time during the disease process has a 96.3% positive predictive value, while a value < 2.0 ng/ml is 97.2% specific for absence of disease. Fifty-three percent of 103 patients had elevated SCC-Ag levels prior to treatment, with the proportion increasing accordingly with advancing stage at diagnosis. In 70 patients with recurrence, 81% had elevated values. Squamous cell carcinoma antigen predicted recurrence an average of 6.9 months prior to detection of clinically evident disease. Patients with initially negative SCC-Ag levels may demonstrate elevated values with tumor recurrence. This marker accurately reflects the response to treatment in patients who have elevated levels prior to treatment. Squamous cell carcinoma antigen is a useful tumor marker in the management of patients with squamous cell carcinoma of the uterine cervix.