The ultrastructural immunohistochemistry of oncofoetal antigens in large bowel carcinomas

Abstract

Seven large bowel carcinomas were examined by light and electron microscopy for the presence of five oncofoetal antigens. Ultrastructural investigations involved a novel method whereby thick sections of gluteraldehyde-fixed material were cut on a vibratome and then labelled using slight modifications of a standard unlabelled antibody-enzyme (PAP) technique, before further processing. Ultrastructural preservation, staining properties and the retention of antigen activity was seemingly better than that achieved by other investigators. Specific, positive labelling for carcinoembryonic antigen (CEA), colon specific antigen (CSA) and pregnancy-specific beta-1-glycoprotein (SP1) was seen in every case. Clear positive labelling for placental alkaline phosphatase (PLAP) and human chorionic gonadotropin (HCG) was seen in two cases. Extracellular labelling was found in areas of cell debris, free lying or in phagocytic cells and on tumour cell brush borders. The pattern of intracellular labelling, however, was different for each antigen and reflected the probable sites of synthesis and release from the cells. Thus CEA, a complex glycoprotein, was localised within the golgi apparatus, small apical cytoplasmic vesicles and mucous droplets in relatively well differentiated tumour cells. CSA, a chemically related glycoprotein, had a similar, but less dense distribution. SP1, by contrast, was localised within basally-located vesicles associated with the ribosomal endoplasmic reticulum and appeared to be released and persist as debris or taken up by phagocytic cells below the basal lamina. PLAP and HCG, both proteins, were found within simple single membrane-bound vesicles within relatively undifferentiated cells.

Induced Pluripotent Stem Cell-Based Cancer Vaccines

“…Embryonic stem cells (ESCs) have the ability to undergo rapid clonal proliferation and self-renew, and can inhabit and thrive in various environments of the human body. The similarities between fetal development and cancer have long been recognized (1) following the discovery of oncofetal proteins and antigens such as α-fetoprotein (AFP) (2), carcinoembryonic antigen (CEA) (3), and human chorionic gonadotropic (HCG) (4) (Supplemental Table 1). These proteins are tumor associated proteins or antigens (TAA) that are synthesized during embryonic development and appear again in adults during cancer development.…”

“…These proteins are tumor associated proteins or antigens (TAA) that are synthesized during embryonic development and appear again in adults during cancer development. Furthermore, these proteins are well-known biomarkers for cancer detection and monitoring (3, 5–9). Induced pluripotent stem cells (iPSCs) can be generated by introducing four transcription factors into adult somatic cells, which transform their transcriptional and epigenetic state to a pluripotent one that closely resembles ESCs (10).…”

Strategies for Cancer Immunotherapy Using Induced Pluripotency Stem Cells-Based Vaccines

“…Similarly, to ESCs, iPSCs also share a number of characteristics with CSCs including self-renewal and proliferation, expression of stem cell markers and altered metabolism. The similarities between fetal development and cancer has long been recognized, following the discovery of oncofetal proteins (such as α-fetopotein, carcinoembryonic antigen, human chorionic gonadotropic, for a review see [77]), which are tumor-associated antigens (TAAs) expressed during embryonic development and re-acquired in adults during cancer [78]. Human iPSCs share genetic and transcriptomic signatures with cancer tissues, including several cancer-related genes and more than 100 human TAAs and tumor-specific antigens (TSAs), which are protein markers that can be recognized by the immune system [79,80].…”

An enzyme immunoassay for pregnancy-specific β-1 glycoprotein (SP1), employing monoclonal antibodies

“…In addition, many tumors including breast (Wurz et al, 1979), colorectal (Haynes et al, 1985) and lung (Grudzinskas et al, 1980;Boucher and Yoneda, 1995) cancers have been reported to produce SP1. However, many reports on the correlation of serum SP1 level with various clinical conditions show considerable discrepancies from reports to reports in each cancer.…”