RESUMEN
DS6 is a murine monoclonal antibody developed using ovarian papillary serous adenocarcinoma as the immunogen. DS6 immunohistochemically reacts with a tumor-associated antigen, CA6, which has a limited range of expression in normal human tissues and is not expressed by benign mesothelium. We have studied the spectrum of immunohistochemical reactivity of antibody DS6 in 293 formalin-fixed, paraffin-embedded human gynecological neoplasms. The CA6 antigen shows strong expression in serous adenocarcinomas of the ovary (56/58 cases) and endometrium (6/6). CA6 is also expressed by the majority of ovarian endometrioid adenocarcinomas and Brenner tumors and by the majority of endometrioid adenocarcinomas, mucinous adenocarcinomas, and clear cell adenocarcinomas of the endometrium. CA6 is detected in 14% of ovarian clear cell carcinomas and is not detected in ovarian mucinous cystadenomas (0/7), mucinous intestinal-type borderline tumors (0/8), mucinous adenocarcinomas (0/10), or in malignant mesotheliomas (0/8). In neoplasms with papillary or glandular growth patterns, CA6 is detected along luminal cell membranes. CA6 is also seen along peripheral cell membranes and focally in the cytoplasm in some epithelial neoplasms. There is heterogeneity in immunohistochemical staining for DS6 both within an individual neoplasm and between neoplasms. Reactivity is not detected in neoplasms of sex cord-stromal, mesenchymal or germ cell origin.
Asunto(s)
Adenocarcinoma/metabolismo , Anticuerpos Monoclonales , Antígenos de Carbohidratos Asociados a Tumores/metabolismo , Neoplasias de los Genitales Femeninos/metabolismo , Adenocarcinoma/patología , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/patología , Femenino , Neoplasias de los Genitales Femeninos/patología , Humanos , Hibridomas , Inmunohistoquímica , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patologíaRESUMEN
A newly developed murine monoclonal antibody, DS6, immunohistochemically reacts with an antigen, CA6, that is expressed by human serous ovarian carcinomas but not by normal ovarian surface epithelium or mesothelium. CA6 has a limited distribution in normal adult tissues and is most characteristically detected in fallopian tube epithelium, inner urothelium and type 2 pneumocytes. Pre-treatment of tissue sections with either periodic acid or neuraminidase from Vibrio cholerae abolishes immunoreactivity with DS6, indicating that CA6 is a neuraminidase-sensitive and periodic acid-sensitive sialic acid glycoconjugate ("sialoglycotope"). SDS-PAGE of OVCAR5 cell lysates has revealed that the CA6 epitope is expressed on an 80 kDa non-disulfide-linked glycoprotein containing N-linked oligosaccharides. Two-dimensional non-equilibrium pH gradient gel electrophoresis indicates an isoelectric point of approximately 6.2 to 6.5. Comparison of the immunohistochemical distribution of CA6 in human serous ovarian adenocarcinomas has revealed similarities to that of CA125; however, distinct differences and some complementarity of antigen expression were revealed by double-label, 2-color immunohistochemical studies. The DS6-detected CA6 antigen appears to be distinct from other well-characterized tumor-associated antigens, including MUC1, CA125 and the histo-blood group-related antigens sLea, sLex and sTn.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Antígenos de Neoplasias/análisis , Cistadenocarcinoma Seroso/inmunología , Neoplasias Ováricas/inmunología , Antígenos de Neoplasias/efectos de los fármacos , Cloroformo/farmacología , Electroforesis en Gel de Poliacrilamida , Femenino , Humanos , Immunoblotting , Neuraminidasa/farmacología , Ácido Peryódico/farmacologíaRESUMEN
Immunohistochemical analysis of biopsies, cytology specimens or surgical resection specimens using antibodies directed towards tumor-associated antigens, lineage or differentiation antigens is a technique often used by surgical pathologists to aid in establishing the correct histologic classification of malignant tumors. With the proliferation of experimental approaches to cancer treatment using monoclonal antibodies as targeting agents, it is anticipated that surgical pathologists will increasingly be receiving requests from clinicians to define the antigen profile in biopsy specimens, even when not necessary to render the correct tumor classification. Clinicians may use the immunohistochemically delineated antigen profiles provided by surgical pathologists to plan tailored treatment regimens utilizing monoclonal antibodies to the antigens expressed in the tumor biopsy to target anticancer therapeutic agents. Some of the potential problems in such a process might include the differing sensitivities, and perhaps specificities, of the antibodies used for analyzing the surgical pathology biopsy specimens compared to the monoclonal antibodies actually used in vivo. Our approach to this dilemma is to develop murine monoclonal antibodies to tumor-associated antigens that can reliably be used to detect antigens in routinely processed surgical pathology specimens as a starting point for further therapeutic monoclonal antibody development.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antígenos de Neoplasias/análisis , Cistadenocarcinoma Papilar/inmunología , Inmunohistoquímica , Inmunoterapia , Neoplasias Ováricas/inmunología , Antígenos de Neoplasias/inmunología , Cistadenocarcinoma Papilar/terapia , Femenino , Humanos , Hibridomas/inmunología , Neoplasias Ováricas/terapia , Pruebas de Precipitina , Fijación del Tejido , Células Tumorales CultivadasRESUMEN
Hepatocyte paraffin 1 is a monoclonal antibody that has been developed specifically to react with hepatocytes in routine formalin-fixed and paraffin-embedded surgical pathology tissues. It results in a distinct, granular cytoplasmic staining of hepatocytes but fails to react with bile ducts and nonparenchymal liver cells. The antibody decorates a majority of hepatocellular carcinomas, including fibrolamellar variants. It fails to react with a wide variety of other adult malignancies, with the exception of focal staining in a few gastrointestinal malignancies, including a subpopulation of gastric carcinomas.
Asunto(s)
Anticuerpos Monoclonales , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Hígado/inmunología , Hígado/patología , Adulto , Animales , Diagnóstico Diferencial , Femenino , Humanos , Técnicas para Inmunoenzimas , Ratones , Ratones Endogámicos BALB C , Estudios Retrospectivos , Coloración y EtiquetadoRESUMEN
Following intrahepatic transplantation in adult syngeneic Fischer 344 rats, diploid cultured rat liver epithelial cells (WB-F344), modified to carry the Escherichia coli beta-galactosidase reporter gene and/or the fluorescent membrane dye PKH26-GL, integrate into hepatic plates and acquire the size and nuclear structure of mature hepatocytes. Additionally, of two aneuploid, neoplastically transformed derivatives of WB-F344 cells, both of which produce aggressively growing tumors when transplanted subcutaneously, cells of one line (GN6TF) do not produce tumors in the liver but integrate into hepatic plates and morphologically differentiate. The other transformed line (GP7TB) retains tumorigenicity in the liver, but cells in the intrahepatic tumors are more differentiated morphologically than are tumors at subcutaneous sites. These results suggest that WB-F344 cells are stemlike cells for hepatocytes and that the hepatic microenvironment induces them to incorporate into hepatic plates and differentiate. Our results also suggest that the hepatic microenvironment regulates the differentiation of some neoplastically transformed hepatic stemlike cells, thereby eliminating or reducing their tumorigenic potential.