Placental-type alkaline phosphatase in cervical neoplasia

Abstract

Summary Monoclonal antibodies reactive with placental-type alkaline phosphatase have formed the basis of methods for detection of this oncodevelopmental antigen in patients with pre-invasive and invasive cervical neoplasia, with or without evidence of papilloma virus infection. Disease-related elevations of placental-type alkaline phosphatase were not observed in patients' sera. Solubilised cervical smears or biopsy material, and cervical mucus swabs, often contained substantial amounts of this isoenzyme; however, there was no significant difference between any of the patient and control groups. Thus, serological and smear test assays for placental-type alkaline phosphatase were not useful in differential diagnosis of cervical lesions. However, its presence in most biopsy specimens, often at high levels, indicated possible application for in vivo radioimmunoimaging studies of invasive or metastatic cervical cancer.The incidence of cervical cancer has increased markedly in younger women over the last two decades, in part due to venereal transmission of papilloma virus (HPV) infection (Crawford, 1984 (Syrjanen et al., 1985). Screening for pre-invasive cervical carcinoma involves exhaustive examination of smears, and therefore simple rapid techniques for identifying pre-invasive cervical neoplasia are attractive to seek.Potential markers for neoplastic cellular transformation are the oncodevelopmental antigens, such as placental-type alkaline phosphatase. This isoenzyme is a major glycoprotein of term placental trophoblast membranes, and is also expressed on some tumour cell lines including cervical carcinoma cells (McLaughlin et al., 1982). Two major forms of placental-type alkaline phosphatase have been described, the 'placental' and 'placental-like' alkaline phosphatases (PLAP and PLAP-like AP, respectively). These can be distinguished by relative sensitivity to inhibition by L-leucine (Stigbrand et al., 1982) and differential reactivity with certain monoclonal antibodies (mAbs) (McLaughlin & Johnson, 1984).The development of sensitive and specific solid-phase enzyme capture immunoassays (EIA) utilising either the mAb H317 (reactive solely with PLAP) or the mAb H17-E2 (reactive with both PLAP and PLAP-like AP) has broadened investigations of this isoenzyme group in cancer 1984a, b;Epenetos et al., 1985a;Horwich et al., 1985;Tucker et al., 1985). For example, previous serological assays have been limited by detection of elevated isoenzyme levels in healthy individuals, particularly cigarette smokers (Maslow et al., 1983;Tonik et al., 1983). It is now clear that this smoking-associated enzyme is PLAPlike AP, rather than PLAP, and thus ig unreactive in the H317-based assay (McLaughlin et al., 1984b Twelve patients from the Oxford region with established cancer of the cervix were also studied. These had squamous carcinoma (n = 9), adenocarcinoma (n =2) or mixed squamous and adenocarcinoma (n= 1); three of the carcinomas were Stage IA, five were Stage IB, three were IIA, and one was IIB. Monoclonal antibodies (mAbs...

A novel placental like alkaline phosphate promoter driven transcriptional silencing combined with single chain variable fragment antibody based virosomal delivery for neoplastic cell targeting

“…PLAP is most frequently expressed in germ cell tumours [ 10 ], cervical cancer [ 11 ], ovarian cancer [ 12 ], but not generally in normal tissue with only a negligible degree of expression in normal cervix [ 13 ]. The ectopic expression of PLAP in malignantly transformed colon cancer cell lines has been studied by Deng and co-workers [ 14 ] who have extensively analysed PLAP promoter activity in the cells.…”