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Biomedical subjects

K S McCarty

Publications and source records attributed to K S McCarty.

At least 91 records · Page 5Linked to original sources

Immunoglobulin localization in the normal human mammary gland: variation with the menstrual cycle.

Differences in immunoglobulin localization (IgG, IgM, IgA) in benign versus malignant lesions of the human mammary gland have been previously demonstrated. The present investigation was undertaken to evaluate the influence of menstrual cycling on these immunoglobulins in the breast. Tissues were studied from 53 normal breasts. The patients were 16 to 51 years old, with a mean age of 35 +/- 9 years, and were documented as having regular menstrual cycling, lack of debilitating disease, and abstinence from use of hormones or from medications that might influence the pituitary-ovarian axis. Immunoglobulin localization in the tissue section was determined by direct immunofluorescence with antibodies specific for IgG, IgA, IgM, and IgA secretory component. The breast tissues were categorized into 5 histologically distinct menstrual cycle phases. No significant IgG localization was noted. IgA concentration was noted principally in the preovulatory phase of the cycle (P less than 0.03). IgM showed a similar variance, and IgA secretory component paralleled IgA localization. No correlation between IgA and IgM localization and plasma cells infiltration nor between plasma cell infiltration and menstrual cycle phase could be documented. These data suggest that menstrual cycling influences the human breast as part of the secretory immune system.

Adolescent↗

Biochemical correlates of morphologic differentiation in human breast cancer.

In 115 breast carcinoma tissues, histologica grade and cell cytosol concentrations of estrogen receptor (ER) and progesterone receptor (PR) and two breast cyst fluid proteins (gross cystic disease fluid protein [GCDFP-15] and nonreceptor progesterone-binding protein [PBP]) were deterMined. Higher levels (expressed as femtomoles per milligram of protein) of ER (128 +/- 28 versus 11 +/- 1, P less than 0.001) and PR (82 +/- 16 versus 3 +/- 1, P less than 0.001) were found in grade 1 (well-differentiated) carcinomas as compared with grade 3 (poorly differentiated) carcinomas. Similarly, higher concentrations (expressed as nanograms per milligram of cytosol protein) of GCDFP-15 (2110 +/- 840 versus 210 +/- 40, p less than 0.001) and PBP (4920 +/- 1200 versus 370 +/- 60, P less than 0.001) were found in grade 1 as compared with grade 3 carcinomas. Tumor cytosols that contained low levels of both cyst proteins (less than 225 ng/mg GCDFP-15 and less than 750 ng/mg PBP) had a high incidence of grade 3 (35 of 46, 78%) or grade 2 (15 of 46, 33%) histologic findings and had a high incidence of receptor-negative specimens (27 of 52, 52%). Based on these cutoff levels, grade 2 lesions were subdivided into a "high" cyst protein group, which had ER and PR levels similar to grade 1 tumors (93.1 +/- 26.7 for ER and 84.7 +/- 32.4 for PR, P greater than 0.3), and a "low" group, which had receptor values similar to grade 3 carcinomas (14.1 +/- 5.3 for ER and 9.1 +/- 5.2 for PR, P less than 0.3). Although the mean cytosol content of carcinoembryonic antigen (CEA) was significantly higher in malignant tissues (125 +/- 27 ng/mg cytosol protein) than in benign tissues (4.8 +/- 1 ng/mg cytosol protein), the CEA content was not significantly different between grades 1 and 3 tumors.

Apolipoproteins↗

Immunoglobulin localization in benign and malignant lesions of the human mammary gland.

Using direct imunofluorescence, lesions from 266 human breast specimens were studied for the presence of IgA, IgM, or IgG localization. The lesions included benign elements from 66 subcutaneous mastectomy specimens in which the absence of simultaneous breast malignancy was documented, primary breast carcinomas from 153 mastectomy specimens, and 47 biopsies containing metastatic breast cancer. A statistically significant association of IgA and IgM with benign lesions was contrasted to the association of IgG with malignant lesions. In both primary and metastatic lesions, IgG localization was associated with estrogen-receptor-poor primary cancers as compared with estrogen-receptor-rich primary cancers. Among primary breast cancer patients, IgG localization in the tumor correlated with relative lymphopenia. A shorter disease-free interval was noted in association with IgG localization among the metastatic breast lesions. No statistically significant association between stage of disease and immunoglobulin presence was demonstrable. Moderate-to-severe intraductal epithelial hyperplasias were more often associated with immunoglobulin G localization that were other benign lesions.

Adult↗

Adrenocorticotropin production by a mammary carcinoma.

A patient with clinical hypercortisolism and an infiltrating ductal carcinoma of the right mammary gland is presented. Provocative testing of adrenal function demonstrated the pattern of ectopic adrenocorticotropic hormone (ACTH) production. Ultrastructural analysis of the tumor revealed 150-200 nm electron-dense granules that when primarily fixed in OsO4 appeared as membrane-bound, centrally dense cored granules. ACTH was extracted from the tumor tissue and immunocytochemically localized in the tumor cell cytoplasm. A clinically significant level of estrogen receptor protein was present in the tumor tissue (120 fmol/mg protein). This case confirms the ability of mammary carcinoma to produce the ectopic ACTH syndrome.

Adrenalectomy↗

Modified radical mastectomy with immediate reconstruction for carcinoma of the breast.

Fifty patients undergoing immediate reconstruction of the breast following modified radical mastectomy for carcinoma were characterized by their clinical findings and the pathologic features of their tumors. Evidence of nipple--areolar involvement by tumor was noted in five patients. This high incidence mitigates against nipple--areolar transplantation. In ten patients the breast contained multifocal tumor or intraductal carcinoma away from the primary tumor, thus emphasizing the importance of careful evaluation of the total tissue specimens. Four patients have had recurrence of tumor. The detection of the recurrence was not hindered by the presence of the prosthesis. In these four patients immediate reconstruction of the breast did not appear to adversely affect the natural history of the breast cancer. We suggest that when appropriate and thorough surgical extirpation followed by reconstruction is undertaken as a team effort among the general and plastic surgeons, pathologist and clinical psychologist, the optimal clinical and cosmetic results may be achieved. However, conclusive statements regarding the long-term implications of immediate reconstruction awaits additional follow-up.

Adult↗

Hormone responsiveness of a transplantable rat chondrosarcoma: III. ultrastructural evidence of in vivo hormone dependence.

The effects of growth hormone (GH) and/or cortisone and thyroxine (T4) treatment on the ultrastructure of the transplantable Swarm rat chondrosarcoma grown in hypophysectomized rats were studied. Marked atrophy of the tumor occurred when it was grown in hypophysectomized rats. Maximal restoration of tumor growth in hypophysectomized rats was achieved when cortisone, T4, and GH were administered in combination. An intermediate degree of tumor growth restoration was observed when tumor-bearing hypophysectomized rats were given cortisone and T4 or GH alone. Cortisone and T4 treatment was associated with increased rough endoplasmic reticulum and nucleolar enlargement, while GH treatment was associated with marked dilatation of the endoplasmic reticulum. When GH, cortisone, and T4 were given in combination, a marked increase in exocytotic/pinocytotic vesicles and apparent deposition of cartilage matrix were noted. The data indicate that GH has dramatic influences on the tumors and, when GH, cortisone, and T4 are administered together, these hormones have a synergistic effect on the growth of the Swarm rat chondrosarcoma.

Animals↗

The correlation of histologic changes in the human breast with the menstrual cycle.

Histologic changes in the normal human mammary gland associated with the menstrual cycle were sought in tissues derived from a defined population of patients undergoing subcutaneous mastectomy or reduction mammoplasty for reasons other than neoplasia. Ninety patients were selected for their regular menstrual cycling, abstinence from hormone use, and absence of disease which might influence pituitary-ovarian cycling. Morphologic changes in the mammary stromal and epithelial components were identified as they related to specific pituitary-ovarian events, and histologic criteria were identified that allowed reproducible morphologic categorization of the mammary gland into five specific phases: proliferative (Days 3-7); follicular phase of differentiation (Days 8-14); luteal phase of differentiation (Days 15-20); secretory (Days 21-27); and menstrual (Days 28-2). Double-blind reviews of tissues confirmed the validity and the reproducibility of these histologic criteria in identifying the menstrual phase. The findings further characterize the morphologic correlates of hormone responsiveness of the normal human mammary gland. The recognition of menstrual-cycle-dependent histologic changes may be expected to provide a basis for extending the interpretation of the morphologic characteristics of the breast in surgically acquired specimens that may be associated with hormonal aberrations.

Adolescent↗

Comparison of biochemical and histochemical techniques for estrogen receptor analyses in mammary carcinoma.

Three histochemical techniques for estrogen binding localization in tissue sections were compared to sucrose density gradient analyses for estrogen receptor in 186 breast carcinomas. Apparent localization to epithelial elements was noted using 6-BSA-Fluor-CMO-17 beta-estradiol, 17-BSA-Fluor-TSC-estrogen, and polyestradiol phosphate/anti-estradiol antibody methods. The correlation between the histochemical methods and standard sucrose density gradient techniques was poor for the polyestradiol antibody method and the 6-BSA-fluor-CMO-17 beta-estradiol techniques. While an improved correlation was observed with the 17-BSA-Fluor-TSC-estrogen compound, the compound's binding was not effectively blocked by preincubation with diethylstilbestrol. This failure to show convincing saturability of binding, combined with problems of extraction of soluble receptor proteins in the aqueous incubation media and washed from cells rendered permeable by cryostat sectioning, indicates that several areas will require clarification before histochemical techniques can begin to be considered as a method for estrogen ""receptor" analyses in the clinical evaluation of breast neoplasms.

Binding, Competitive↗

Comparison of sex steroid receptor analyses and carcinoembryonic antigen with clinical response to hormone therapy.

This study corroborates previous reports which suggested the efficacy of estrogen receptor (ER) analysis in predicting responses of patients with metastatic mammary carcinoma to hormonal therapeutic manipulation. The predictive value of multiconcentration titration and sucrose density gradient analyses of ERs and progesterone receptors (PRs) are compared. The predictive value of ER analyses can be improved by the discrimination of 8S versus 4S binding species or by the use of PR analysis in combination with ER analysis. The tumor-associated antigen, carcinoembryonic antigen (CEA), is evolving as an important quantitative aid in evaluating the clinical responses to patients receiving hormonal therapy.

Adrenalectomy↗

Correlation of estrogen and progesterone receptors with histologic differentiation in mammary carcinoma.

Using a modification of the histologic grading system of the NSABP, we observed a trend towards higher levels of estrogen (E2R) and progesterone receptor (PR) content in well (grade I) and moderately (grade II) differentiated mammary carcinomas. This relationship between receptor content and histologic grade is enhanced by considering estrogen and progesterone receptor simultaneously. The rank correlation between the quantitative levels of E2R and PR was 0.74 among histologic grade I tumors and 0.64 among histologic grade II tumors. Among the grade III carcinomas, the majority of tumors displayed either a paucity of measurable receptor or a divergence between levels of estrogen versus progesterone receptor (r = 0.19). The use of ultrastructural evaluation of features of differentiation is discussed in the evaluation of grade III tumors and in the evaluation of specific histologic types of mammary carcinoma.

Adenocarcinoma↗

Apocrine differentiation in human mammary carcinoma.

Six invasive carcinomas that contained apocrine differentiation as the primary morphologic pattern were selected from a series of 1500 prospectively examined breast carcinomas (0.4%). While apocrine features were seen in many breast tumors, these six cases were identified by uniformly fine granular, pale, eosinophilic cytoplasm with apical cytoplasmic projections similar to that seen in apocrine metaplasia. In each example, ultrastructural analysis revealed the presence of numerous 400-600 nm membrane bound vesicles with dense homogeneous osmophilic cores. These granules clustered toward the apex of the cytoplasm in the majority of the epithelial cells. All six tumors were deficient in high-affinity, low-capacity 8S estrogen and progesterone proteins, while a high-capacity, low-affinity, nonsaturable 4S progesterone-estrogen binding protein was observed. Cortisol did not bind to this protein. These observations characterize the ultrastructure of apocrine carcinoma as a variant of human mammary carcinoma.

Apocrine Glands↗