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Biomedical subjects

L P Pertschuk

Publications and source records attributed to L P Pertschuk.

At least 19 recordsLinked to original sources
PubMed1991

Comparison of microscopic imaging strategies for evaluating immunocytochemical (PAP) steroid receptor heterogeneity.

Receptogram analysis was compared with three other imaging strategies for immunocytochemical assay of estrogen receptors. These included nuclear-specific methods for analysis of nuclear integrated optical density (IOD) or mean optical density (MOD) histograms, and field-specific methods, where the pixel optical density (POD) histogram was evaluated for the composite nuclear phase. Measurements in culture and in breast cancer cryosections were treated separately to isolate geometric considerations. In culture receptograms the modality of IOD and MOD histograms and their bivariate contour maps revealed one, two, or more subpopulations with discrete receptor content and concentration. However, when the field of nuclei was imaged as a whole, regardless of the number of subpopulations, POD histograms showed two minima, defining three intranuclear phases. This was due to mottling and variegation of intranuclear chromatin and nucleolar immunostaining and not to differences between nuclei. These limitations were also revealed in breast cancer sections. In POD histograms, % unstained pixels did not provide a reliable estimate of % receptor negative nuclei, as determined by their enumeration. In sections, correction of IOD for nuclear volume variability was essential to suppress artifactual peaks not representing differences in receptor content. This was achieved by multiplying nuclear IOD by the spherical nuclear radius (S) of individual slab sections. Peaks of IOD(S) then reflected receptor content on a true ratio scale. Only receptogram analysis, which incorporates these strategies, permitted objective evaluation of receptor heterogeneity at the level of tumor subpopulations.

Breast Neoplasms↗
PubMed1990

Immunocytochemical estrogen and progestin receptor assays in breast cancer with monoclonal antibodies. Histopathologic, demographic, and biochemical correlations and relationship to endocrine response and survival.

Breast cancer specimens from 600 women were assayed for estrogen receptors (ER) using an immunocytochemical assay (ICA) employing the monoclonal antiestrophilin antibody H222 Sp gamma. Results showed significant correlation with biochemical ER determinations as well as with tumor grade and menopausal status. In 449 cases, results of progesterone receptor assay by ICA using the monoclonal anti-PgR antibody KD 68, also correlated significantly with biochemical PgR measurements. The ERICA/PgRICA positivity was significantly more frequent in postmenopausal white women. Colloid carcinomas were most likely to be ERICA positive and PgRICA positive whereas medullary carcinomas were most often negative. In 47 patients with advanced mammary carcinoma, results of ERICA and PgRICA were more closely related to endocrine response than those of ER and PgR by dextran-coated charcoal assay (DCC). In 339 women with Stage I or Stage II breast cancer, ERICA was significantly associated with disease-free survival. Analysis by Cox's proportional hazard model, however, showed PgRICA to be the best predictor of survival and disease-free survival in 197 women at the same stages of disease. These data indicate that ICA is more predictive of prognosis than biochemical ER and PgR. The ease of ICA performance coupled with these results indicate that the method is an acceptable substitute for DCC in analyzing breast cancers for ER/PgR.

Adult↗
PubMed1990

Quantitative imaging of immunocytochemical (PAP) estrogen receptor staining patterns in breast cancer sections.

"Receptogram Analysis" has been developed as a pattern-oriented approach for predicting endocrine response in breast cancer based upon quantification of the estrogen receptor immunocytochemical assay (ERICA), using a Quantimet Imaging System. Response prediction was evaluated in 58 stage III and IV patients receiving endocrine therapy (primarily Tamoxifen). The Receptogram is a composite of the univariate distributions of nuclear receptor content, IOD(S), and concentration (MOD), and their bivariate contour plot; where (S) is the calculated nuclear radius in section. MOD distributions were classified into four types based upon peak modality and kurtosis (I-IV), and contour plots were classified into four subtypes (A-D) based upon contour slope. Patients failing therapy were ERICA--or their receptogram revealed co-existent ER+ and ER- tumor cells (type II), highly skewed MOD distributions lacking defined peaks (type IV), or contours with nearly horizontal slope (type C). Response was realized in 9/16 type I patients, with a single positive MOD peak, and in 9/15 type III patients, with discrete, multimodal MOD peaks. In contrast, 0/8 type II, 0/12 type IV, and 0/10 type C patients were responders. Receptogram analysis was superior to cytosol assay (DCC) as a response discriminant: positive predictive value, 53% vs. 33%; negative predictive value, 100% vs. 75%; sensitivity, 100% vs. 83%; specificity, 68% vs. 23%; and accuracy, 78% vs. 41%, respectively. Alternately, patients were assigned to potentially responsive or non-responsive groups based upon thresholded mean receptor parameters: field MOD, mean nuclear MOD (NMOD), and mean NMOD(PF) where PF is the ER+ nuclear fraction. While these parameters correlated with DCC (r = .72, 0.69, and 0.69), they were only marginally better in predictive value.

Adult↗
PubMed1979

Strumal carcinoid of the ovary: an analysis of its components.

A strumal carcinoid of the ovary was studied by light and electron microscopy. Thyroglobulin was demonstrated within the strumal element by immunofluorescence, thus establishing the identity of the thyroid tissue. The carcinoid fulfilled the light and electron microscopic criteria for a mixed insular and trabecular example of this tumor. Intermediate zones between the two tissue elements showed mixed characteristics. No amyloid was found. Immunoreactive calcitonin was demonstrated in the tumor, suggesting the presence of C-cells or medullary carcinoma of the thyroid.

Aged↗
PubMed1979

Immunofluorescent localization of angiotensin converting enzyme in epithelioid and giant cells of sarcoidosis granulomas.

Angiotensin converting enzyme (ACE) (dipeptidyl carboxypeptidase; peptidyldipeptide hydrolase, EC 3.4.15.1) was localized in epithelioid and giant cells within ACE-rich sarcoidosis granulomas, but not control granulomas, by immunofluorescence by using a rabbit anti-human ACE immunoglobulin for localization and fluorescein-labeled goat anti-rabbit immunoglobulin for detection. ACE was frequently not detected in the very central epithelioid cells, perhaps due to a paucity of cellular or molecular stimulatory interaction in this region. The results suggest that marked elevation of ACE in the granulomas and often in the serum in sarcoidosis may be due to intense induction of ACE in most epithelioid and giant cells of the sarcoidosis granulomas.

Fluorescent Antibody Technique↗
PubMed1979

An improved histochemical method for detection of estrogen receptors in mammary cancer. Comparison with biochemical assay.

Unselected, consecutive surgical specimens from 120 women with cancer of the breast were subjected to histochemical assay for the presence of estrogen receptor. A fluoresceinated bovine serum albumin--estradiol conjugate was used that linked estradiol at position 17 and contained 5 mol fluorescein and 4 mol estradiol per mole albumin. Simultaneous competitive binding studies with excess unlabeled estradiol, diethylstilbestrol, and the antiestrogen nitromifene citrate were regularly performed. Results were compared to those obtained by the dextran-coated charcoal receptor assay. Three specimens were necrotic, two others thawed, and two lacked sufficient protein for biochemical analysis. One specimen did not contain tumor, and 11 others showed a predominant nuclear staining pattern. Nuclear receptor was not assayed biochemically. Comparison of results in the remaining 101 cases showed agreement in 92%. The precedure is uncomplicated, economical, and could be performed and interpreted in any pathology laboratory.

Binding Sites↗
PubMed1979

A histochemical technique for evaluation of progesterone receptors in breast cancer.

A histochemical method for the detection and localization of progesterone receptors in human breast cancer has been developed employing a fluorescein labeled conjugate of bovine serum albumin linked to a progestin as the binding hormone. Considerable tumor cell receptor heterogeneity was apparent and nuclear binding was frequently noted. The results of the new assay correlated with those obtained by dextran-coated charcoal assay in 91 per cent of specimens.

Breast Neoplasms↗
PubMed1979

Lysosomes in Brenner's tumor simulating secretory argentaffin granules.

Argentaffin cells were searched for in the epithelial nests of 30 Brenner's tumors, with the Fontana-Masson stain for the screening. Although these cells were found in five tumors, ultrastructural examination of one case, in which the argentaffin cells were multiple, identified the cytoplasmic granules as lysosomes and not as amine precursor uptake and decarboxylation (APUD)-type granules. We conclude that the epithelial component of Brenner's tumors consists of urothelium only and does not include the cells containing argentaffin APUD-type granules.

Brenner Tumor↗
PubMed1978

Immunofluorescent detection of estrogen receptors in breast cancer. Comparison with dextran-coated charcoal and sucrose gradient assays.

Biopsy specimens from 106 women with primary operable, recurrent or metastatic breast cancer were analyzed in a double blind study designed to compare the results of a new fluorescent antibody method for detection of estrogen receptors with estrogen receptors measured biochemically with dextran-coated charcoal and sucrose gradient assay techniques. Assay results correlated in 89.4% of tumors analyzed, and molecular receptor forms (8S and 4S) were accurately predicted in 94.7% of neoplasms studied. Divergent results most often occurred in specimens sparsely populated with malignant cells. The new technique permitted recognition of possible sources of false negative results such as necrosis, absence of tumor and, on occasion, estrogen bound in vivo. It was possible to analyze by the immunofluorescence method two specimens of insufficient size for biochemical assay.

Breast Neoplasms↗
PubMed1978

Methadone detection in rat myenteric plexus: comparison with findings in the central nervous system by the immunofluorescence method.

Nonpregnant and pregnant rats were given methadone for varying time periods. Myenteric plexus was then examined for methadone by immunofluorescence and the results compared to similar studies of the central nervous system. Nonpregnant animals showed positive ganglion cells 2 weeks before methadone was detected in the brain. Additionally, maternal ganglion cells were more frequently positive than those of their offspring. These findings indicate fundamental differences in the response of peripheral and central neurons to methadone. Thus, studying the effects of opiates on isolated strips of bowel may be of little value in furthering understanding of the action of narcotics upon the brain.

Animals↗
PubMed1978

Detection of androgen and estrogen receptors in human prostatic carcinoma and hyperplasia by fluorescence microscopy.

The histochemical detection of androgen and estrogen receptors in human prostatic tissue was achieved employing fluorescein labeled conjugates of bovine serum albumin linked to testosterone and estradiol. Results were compared to those of dextran-coated charcoal and protamine sulfate assays and correlated in 85% of specimens. Early findings include a relatively uniform distribution of receptor in hyperplastic epithelium in contrast to marked tumor cell receptor heterogeneity in cancer. Location of receptor in nucleus and/or cytoplasm was readily determined.

Adenocarcinoma↗