Use of a monoclonal anti-estrogen receptor antibody in the immunohistochemical evaluation of human tumors.

A monoclonal antibody to human estrogen receptor protein (H222 Sp gamma), amplified via immunoperoxidase techniques, was used in the analysis of estrogen receptor in 452 breast carcinomas, 100 endometrial carcinomas, and 15 melanomas. Immunohistochemical evaluation incorporated both intensity and distribution of staining (HSCORE). Quantitative estrogen receptor content was determined by dextran-coated charcoal analysis and sucrose density gradient analysis. In all cases H222 Sp gamma localized in the nucleus of target cells. A semiquantitative correlation existed between HSCORE and biochemical assays for breast and endometrial tissues. The sensitivities and specificities for HSCORE as compared to the biochemical assays ranged from 80 to 95% and from 74 to 94%, respectively. HSCORE correlated with tumor grade for breast and endometrial carcinoma. Immunohistochemical evaluation showed no specific staining in melanomas. The data suggest that immunohistochemical receptor localization provides information complementary to standard biochemical assays in the tissues studied.

Regulatory peptides in neuronal neoplasms of the central nervous system.

Neuronal tumors of CNS were examined immunohistochemically for regulatory peptides. Thirteen ganglion cell neoplasms, one cerebellar ganglioneuroblastoma, one cerebellar neuroblastoma, and four medulloblastomas were studied. Sixteen non-neuronal intracranial neoplasms were examined as controls. Immunoreactive vasoactive intestinal polypeptide (VIP) was observed in seven cases of ganglion cell neoplasm and in the one cerebellar ganglioneuroblastoma. The cerebellar neuroblastoma, all of the medulloblastomas, and all of the non-neuronal intracranial neoplasms were negative. Four additional ganglion cell neoplasms were tested for the presence of neurotensin and somatostatin. Two contained neurotensin. The results suggest that CNS ganglion cell neoplasms share with their extracranial counterparts the production of certain hormonal polypeptides. Since these peptides are presumed to be specific markers for neurons, the immunohistochemical detection of these substances may provide diagnostically useful technique in the diagnosis of such lesions.

Clinical response to hormone therapy correlated with estrogen receptor analyses. Biochemical v histochemical methods.

Estrogen receptor (ER) analysis by sucrose density gradient analysis (SDGA) was compared with histochemical localization of estrogen binding using 6-carbomethoxy-bovine serum albumin-fluorescein isothiocyanode-estradiol (E2-6-CMO-BSA-FITC) (6FE), 17-thiosemicarbozene-BSA-FITC-estrogen (E-17-TSC-BSA-FITC) (17FE), and polyestradiol phosphate-antiestradiol antibody-FITC (PEP) on serial frozen sections of metastatic breast cancer lesions from 72 patients treated with hormonal therapy. A comparison of assays to clinical responses gave the following sensitivities: ER-SDGA, 90%; 6FE, 50%; 17FE, 55%; and PEP, 58%. Specificities were as follows: ER-SDGA, 81%; 6FE, 47%; 17FE, 41%; and PEP, 59%. The SDGA gave the highest predictive value for clinical response, while the predictive value for each of the three histologic techniques approximated that predicted by chance alone. These selected histochemical techniques for ER localization, despite impressive cytologic localization patterns, therefore, do not correlate with clinical response.

gamma-Glutamyl transpeptidase activity in benign and malignant human mammary epithelial lesions. Histochemical evaluation.

gamma-Glutamyl transpeptidase (GGT) has been identified in many tissues. The enzyme is present in normal human serum and is accepted widely as an indicator of liver disease. gamma-Glutamyl transpeptidase has been characterized as a putative hepatocellular carcinoma marker in rats and humans and a similar role is suggested in carcinomas of other tissues, including breast, colon, and ovary. Using a histochemical technique to demonstrate GGT activity, we have defined characteristic staining patterns for 67 normal or benign, and 108 overtly malignant human breast lesions. Transitions between benign, atypical, and malignant tumors were observed as were differences between intraductal and infiltrating components of a tumor. Normal breast epithelium and nondysplastic proliferative lesions were characterized by concentrated apical and luminal staining with weak cytoplasmic activity. Malignant lesions exhibited diffuse cytoplasmic staining when staining was observed.