Placental Alkaline Phosphatase in Pediatric Adrenocortical Cancer

Abstract

The germline R337H mutation in the TP53 gene is considered to be responsible for the increased incidence of adrenocortical tumors (ACTs) in children from Brazil. High level production of hormones in ACTs (>95%) cause virilization alone (60%), Cushing syndrome (<5%), the mixed type (30%), or other rarer manifestations. ACT probably develops owing to events occurring during the final stages of intrauterine life based on the very common early onset of signs and symptoms shortly after birth. In this study, we determined by immunohistochemistry and enzyme assays whether placental alkaline phosphatase (PLAP) is expressed in pediatric ACTs. Immunohistochemical analysis revealed positive p53 expression in 88% of the tested ACTs (29 of 33). PLAP was detected at a slightly lower frequency based on immunohistochemical (17 of 33, 51%) and enzyme activity analyses (9 of 16, 56%). In conclusion, probably at a certain time point during adrenocortical development (end of gestation to early postnatal period), some fetal zone cells survive owing to defective apoptosis and develop into childhood ACT, maintaining some characteristics of the embryonal period, such as PLAP expression. Further studies of PLAP should investigate the functional role, if any, of PLAP in such tumors.

Adrenocortical Carcinoma in Childhood: A Systematic Review

“…IGF2 overexpression on the protein and mRNA levels [ 111 ] has been described for pediatric ACC, although other analyses did not confirm this [ 103 ]. Furthermore, there are distinct molecular features of pediatric ACT that differ from adult ACT, specifically: p53 variants on DNA examination [ 11 , 126 ] and p21 overexpression and abnormal beta catenin distribution at the mRNA level [ 103 ]; higher proliferation index (immunohistochemistry) [ 125 , 127 ]; increased expression of silver-binding nucleolar organizer regions (agNOR type III, immunohistochemistry) [ 127 ]; placental alkaline phosphatase (PLAP) was detected by immunohistochemical analysis in one third of prepubertal ACC [ 128 ]; 1p15 LOH as a widespread finding in pediatric ACT not related to malignancy [ 129 ]. …”

“…placental alkaline phosphatase (PLAP) was detected by immunohistochemical analysis in one third of prepubertal ACC [ 128 ];…”

Adrenocortical carcinoma in children: First population-based clinicopathological study with long-term follow-up

“…A histological substrate to substantiate this theory has not yet been found. Certain biochemical features such as increased expression of iGF-ii and placental alkaline phosphatase (PLAP) that are characteristic of fetal adrenal tissue have been demonstrated in pediatric ACC as well, suggesting a relation between the two (19). however, these features do not seem to be unique to patients under 4 years of age (20).…”

The Physiological and Pathological Role of Tissue Nonspecific Alkaline Phosphatase beyond Mineralization

“…IAP is a heat stable isozyme and more active at pH 9.7. Unlike other AP’s the side chain of IAP lacks terminal sialic acid residues [ 23 ]. IAP is essential for lipids absorption and is involved in reducing inflammation.…”