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Biomedical subjects

K S McCarty

Publications and source records attributed to K S McCarty.

At least 19 recordsLinked to original sources

Magnetic resonance imaging in breast cancer staging.

For many solid carcinomas, high-resolution cross-sectional imaging has changed cancer staging, the evaluation of therapeutic response, the detection of recurrence, and even how therapy is selected and performed. Such imaging has not yet had similar effects on breast cancer. Evaluations of therapeutic response in breast carcinomas have been impeded by the current limited methods of evaluating breast tumor size and extent: clinical palpation, ultrasonography, and mammography. The use of magnetic resonance imaging (MRI) of the breast in the evaluation of breast tumors brings the advantages of high-resolution cross-sectional imaging to breast cancer staging and treatment evaluation and is likely to greatly enhance research efforts in this complex disease. MRI of the breast has evolved to be the most accurate noninvasive technique for local staging of breast cancer. MRI is most accurate in measuring tumor size and detecting multicentric disease. These staging characteristics affect the selection of therapy and initial determination of prognosis; therefore, MRI of the breast can change the assessment of fundamental parameters on which treatment is selected. Because clinical trials of new cancer treatments are predicated on proper and accurate characterization of the tumor, MRI also should affect how clinical trials are performed and evaluated.

Adult↗

Sensitivity of enhanced MRI for the detection of breast cancer: new, multicentric, residual, and recurrent.

Magnetic resonance imaging (MRI) of the breast brings the advantages of high resolution cross-sectional imaging to breast cancer diagnosis, treatment and research: improved cancer detection, staging, selection of therapy, evaluation of therapeutic response in vivo, detection of recurrence, and even the development of new therapies. Until now breast cancer treatment and research has been impeded by the limited means of evaluating the breast cancer in vivo: primarily clinical palpation and mammography of the breast tumor. A review of the initial studies shows that with the use of paramagnetic contrast agents, MRI has a sensitivity of 96 % for detecting breast cancers. MRI detects multicentric disease with a sensitivity of 98 %, superior to any other modality. The ability of MRI to detect recurrent local breast cancer in the conservatively treated breast is nearly 100 %. MRI is capable of monitoring tumor response to chemotherapy and actually guiding therapeutic interventions such as interstitial laser photocoagulation.

Breast Neoplasms↗

Quantitative analysis of the calcium-sensing receptor messenger RNA in parathyroid adenomas.

BACKGROUND: In primary hyperparathyroidism, hypercalcemia fails to suppress adequately secretion of parathyroid hormone by the parathyroid gland, which may result from failure of the cell-surface calcium receptor (CaR) to sense calcium correctly. Quantification of mRNA concentrations should provide important information on the role of expression of Call in primary hyperparathyroidism. METHODS: We have developed a quantitative reverse transcriptase-polymerase chain reaction assay with a competitive template (CaR-M). Amplified cDNAs for CaR and CaR-M are quantified, and the concentration of CaR mRNA is determined from the ratio of CaR-M/CaR versus known CaR-M concentrations. RESULTS: In parathyroid adenomas (n = 12) the CaR mRNA was 19.2 +/- 2.4 (mean +/- SE) fg/ng total RNA (range, 7.4 to 32.8 fg/ng). Extracellular ionized calcium levels ranged from 1.38 to 1.74 mmol/L (normal 1.19 to 1.31 mmol/L) and parathyroid hormone from 69 to 345 pg/ml (normal, 14 to 65 pg/ml). In spite of the wide variability in CaR expression in the various adenomas, there was no correlation between mRNA and either extracellular ionized calcium (r2 = 0.013) parathyroid hormone levels (r2 = 0.001). Normal human parathyroid glands gave values of 8.0 and 16.6 fg/ng, whereas normal bovine parathyroid glands had a mean of 20 +/- 0.6 fg/ng (n = 4). CONCLUSIONS: There is no apparent relationship between CaR mRNA levels in adenomas and preoperative Ca and PTH levels. Our findings suggest that defective Ca sensing in adenomas may involve post-translational modification or signal transduction distal to the receptor. Our highly sensitive assay for CaR mRNA should prove useful in examining further the role of CaR in Ca sensing in parathyroid tissue.

Adenoma↗

Breast cancer measurements with magnetic resonance imaging, ultrasonography, and mammography.

BACKGROUND: Accurate measurement of the size of breast cancers becomes more important as breast cancer therapy advances. This study reports the accuracy of magnetic resonance imaging (MRI), ultrasonography and mammography for measuring the largest breast cancer diameter in comparison to the pathology measurement. MATERIALS AND METHODS: Fourteen breast cancers were examined in 13 women with MRI, ultrasonography and mammography. The age range was 31-73 (mean 56). Six of the cancers were in premenopausal women. The MRI was performed with the intravenous injection of gadolinium based contrast agent and a three dimensional fast spoiled gradient echo sequence with fat suppression. The largest cancer diameter was measured with each imaging technique and compared to the largest cancer diameter measured at pathology. RESULTS: At pathological examination cancers ranged from 0.6 to 6 cm (mean 2.2) in largest diameter. MRI measurements had the highest correlation coefficient (r = 0.98) and the smallest standard error (0.34). Ultrasonography measurements had a correlation coeffient of r = 0.45 and a standard error of 0.78. Mammography measurements had a correlation coefficient of r = 0.46 and a standard error of 1.04. CONCLUSIONS: MRI was more accurate than ultrasonography and mammography in measuring the largest cancer diameters in this group of women. This was particularly evident for several larger cancers, and a postchemotherapy cancer.

Adenocarcinoma↗

Technologic considerations for breast tumor size assessment.

Breast tumor staging and treatment response is primarily determined by tumor size. Presently there are four techniques to measure breast cancer size: (1) palpations, (2) mammography, (3) ultrasonography, and (4) MR imaging. This article reviews the applications and limitations of each technique and the improvements MR imaging can provide.

Breast Neoplasms↗

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.

Adult↗

Hormone-resistant endometriosis following total abdominal hysterectomy and bilateral salpingo-oophorectomy: correlation with histology and steroid receptor content.

Endometriosis is rare after hysterectomy and oophorectomy for conditions unrelated to endometriosis. We present a case of delayed development of aggressive, hormone-resistant endometriosis temporally remote from hysterectomy and oophorectomy performed for chronic pelvic inflammatory disease. Treatment with depo-medroxyprogesterone acetate resulted in continued growth of the retroperitoneal endometrioma and necessitated posterior exenteration because of the endometrioma's location. Estrogen and progesterone receptor levels were measured to clarify why this woman's endometriosis was resistant to hormone therapy. Despite administration of large amounts of depo-medroxyprogesterone acetate, the progesterone receptor content was elevated while the estrogen receptor content was undetectable. Why this patient developed this particular type of aggressive endometriosis is unclear, but the lack of down-regulation of progesterone receptors in response to high-dose progestin therapy may indicate an alteration in basic regulatory and cellular processes within the endometriotic implant.

Adult↗

Estrogen and progesterone receptor content of endometrial carcinomas: comparison of total tissue versus cancer component analysis.

Estrogen (ER) and progesterone (PgR) receptor values in 105 endometrial carcinomas were compared using immunocytochemical and standard biochemical techniques. Peroxidase-antiperoxidase staining for location of anti-ER (H222) and anti-PgR (JZB39) primary antibodies was used to generate a semiquantitative (HSCORE) assessment of receptor content in tissue components and the total specimen. Both total HSCORE and cancer component HSCORE correlated with log biochemical assay values for ER and PgR. Biochemical assay values, total HSCORE, and cancer component HSCORES all demonstrated internal correlations between ER and PgR levels. Correlation was somewhat closer for cancer component HSCORE values of ER and PgR than the values for total tissue HSCORE. When receptor content was analyzed by histologic grade, all three estimates of receptor status demonstrated a decreasing proportion of ER and PgR positive lesions with decreasing histologic differentiation; however, the proportion of receptor negative lesions in grade 3 lesions was much higher when using total HSCORE or cancer component HSCORE than when using biochemical assay values (P less than 0.005. Immunocytochemical techniques for localization of ER and PgR in endometrial carcinoma specimens may allow a more focused evaluation of the receptor content in the malignant elements than standard biochemical techniques.

Adenocarcinoma↗

Long-term prognostic implications of sex-steroid receptors in human cancer.

Progesterone receptor analysis has been used to enhance the prognostic usefulness of estrogen receptor analysis in breast cancer. Immunocytochemical assays for both steroid receptors have been shown to correlate with established biochemical techniques but lack long term clinical follow-up studies to validate their use. One hundred fifty- two patients were followed for up to 10 years after primary surgical treatment. Steroid receptor analyses, using both biochemical and immunocytochemical techniques were performed on their tumor specimens. Patients with estrogen or progesterone receptor positive tumors had longer survival than patients with negative tumors. This difference was most clearly demonstrated with immunocytochemical analysis of estrogen receptors (p = 0.04). The two methods for progesterone receptors gave very similar results. Use of multivariate analysis revealed that ER by immunocytochemical analysis was the only significant predictor of prognosis when all four variables were considered simultaneously (p = 0.04). This study suggests that immunocytochemistry gives comparable results to biochemical analysis for progesterone receptors but that immunocytochemical analysis of estrogen receptors was the stronger single prognostic indicator of the four.

Breast Neoplasms↗

Cystosarcoma phyllodes. Effective therapy with cisplatin and etoposide chemotherapy.

Cystosarcoma phyllodes is an unusual breast neoplasm that rarely metastasizes. Most series report chemotherapy, radiation, and hormonal therapy to be ineffective. Three patients were treated with cisplatin and etoposide combination chemotherapy with effective palliation in two patients. Radiation therapy was effective in controlling symptomatic metastasis in all three patients. Hormonal therapy was ineffective in two patients despite the presence of positive hormone receptors. Chemotherapy and radiotherapy may be more effective in the treatment of this tumor than has been reported, although there is no apparent role for hormonal therapy. Functional hormone receptors are probably not present.

Adult↗

Immunohistochemical expression of CA 125 in endometrial adenocarcinoma: correlation of antigen expression with metastatic potential.

Immunohistochemical localization of CA 125 using murine monoclonal antibody OC 125 was performed on fresh frozen tissue from 44 endometrial adenocarcinomas and 26 benign endometria. Immunohistochemical evaluation incorporated both intensity and distribution of staining (CA 125 HSCORE). Thirty-seven cancers (84%) and 23 benign endometria (88%) expressed immunohistochemically detectable CA 125. Staining was confined to epithelial cells and was present both on the cell membrane and in the cytoplasm. Among the 44 endometrial cancers, CA 125 HSCORE did not correlate with histological grade, depth of myometrial invasion or estrogen/progesterone receptor levels. Following surgical staging, 13 patients (30%) were found to have extrauterine metastatic disease. The median CA 125 HSCORE of patients with metastatic disease (2.25) was significantly higher than that of patients with disease confined to the uterus (0.6) (P less than 0.001). In addition, high CA 125 HSCORE also correlated with the presence of lymph node metastasis (P less than 0.001). The results of this study suggest that high CA 125 expression by endometrial adenocarcinomas is associated with increased metastatic potential.

Adenocarcinoma↗

Immunocytochemical analysis of estrogen receptors as a predictor of prognosis in breast cancer patients: comparison with quantitative biochemical methods.

Biochemical quantitation of estrogen receptors has been used to predict prognosis in breast cancer. Immunocytochemical analysis of estrogen receptors correlates with biochemical analysis but has very few follow-up studies in the literature to validate it as a prognostic indicator. 257 patients were followed for up to 10 years (median, 6.2 years) after primary surgical treatment. Estrogen receptor analysis using both biochemical and immunocytochemical techniques was performed on their tumor specimens. Patients with positive estrogen receptor values had longer survival than patients with negative values. This was demonstrated by both methods in the first 5 years of follow-up but only by immunochemistry after 5 years. The relationship between estrogen receptor status and disease-free interval was less strong than with survival. This study demonstrates that immunocytochemical estrogen receptor analysis was of prognostic significance.

Biomarkers, Tumor↗

Heterogeneity of antigen expression in benign and malignant breast and ovarian epithelial cells.

Expression of II distinct antigen families has been studied in normal and malignant epithelial cells from breast and ovary by avidin-biotin immunoperoxidase staining of frozen tissue sections. Each of the antigens was expressed in a fraction of the normal and malignant breast tissues from different individuals. Among breast and ovarian cancers, a similar fraction of tumors expressed each of the determinants. An epitope on a 42-kDa glycoprotein was expressed significantly more often by ovarian carcinomas than by benign ovarian epithelium. Several determinants on 66-, 240-kDa or high-molecular-weight proteins or glycoproteins were expressed significantly more often on benign breast epithelium than on normal ovarian epithelium. Substantial heterogeneity in antigen expression was observed among different tumor specimens. Each of 14 epithelial ovarian cancers expressed a distinctive combination of antigens. Among 18 breast cancers, 16 distinct antigenic phenotypes were observed. Interestingly, comparable heterogeneity was observed in the expression of epitopes on benign breast and ovarian epithelium, compatible with the possibility that the monoclonal reagents recognized polymorphic determinants. Substantial variations in antigen expression were also observed among cells within each neoplasm. However, when antibodies against 5 different determinants were used in combination, a majority of cells could be stained intensely in all 13 breast carcinomas tested and more than 95% of tumor cells could be stained in 10 of the 13.

Antigens, Neoplasm↗

Epidermal growth factor receptor expression in normal and malignant endometrium.

Epidermal growth factor receptor expression in fresh-frozen uterine tissues was studied with the use of monoclonal antibody 528, which recognizes an epitope on the external domain of the epidermal growth factor receptor. Immunohistochemically detectable epidermal growth factor receptor was seen in all uterine cell types in 19 of 20 normal uteri. Staining of endometrial glands and endometrial stromal cells was consistently greater than that of myometrium, and no variation in intensity or distribution of staining was seen during the menstrual cycle. Immunohistochemically detectable epidermal growth factor receptor was found less frequently in endometrial adenocarcinomas than in normal endometrium (p less than 0.01). Thirteen of 40 endometrial adenocarcinomas (32.5%) did not express detectable receptor. Epidermal growth factor receptor expression did not correlate with histologic grade, depth of myometrial invasion, estrogen-progesterone receptor status, the presence of extrauterine metastases, or the development of recurrent disease.

Adenocarcinoma↗