Immunohistochemistry Study of P53 and C-erbB-2 Expression in Trophoblastic Tissue and Their Predictive Values in Diagnosing Malignant Progression of Simple Molar Pregnancy

Abstract

Background: Finding a tumor marker to predict the aggressive behavior of molar pregnancy in early stages has yet been a topic for studies.

Objectives: In this survey we planned to study patients with molar pregnancy to 1) assess the p53 and c-erbB-2 expression in trophoblastic tissue, 2) to study the relationship between their expression intensity and progression of a molar pregnancy to gestational trophoblastic neoplasia, and 3) to determine a cut off value for the amount of p53 and c-erbB-2 expression which might correlate with aggressive behavior of molar pregnancy.

Patients and methods: In a prospective cross sectional study by using a high accuracy technique EnVision ^Tm system for immunohistochemistry staining of molar pregnancy samples, we evaluated p53 and c-erbB-2 expression in cytotrophoblast and syncytiotrophoblast and the correlation of their expression with progression of molar pregnancy to gestational trophoblastic neoplasia (GTN). Normal prostatic tissue and Breast cancer tissue were used as positive controls.

Results: We studied 28 patients with simple molar pregnancy (SMP) and 30 with GTN. Cytotrophobalst had significantly higher expression of p53 and c-erbB-2 and syncytiotrophoblast had greater expression of p53 in GTN group as compared to SMP group. The cut off values for percentage of p53 positive immunostained cytotrophoblast and syncytiotrophoblast were 5.5% and 2.5%. In c-erbB-2 positive membranous stained cytotrophoblast the cut off was 12.5%.

Conclusions: Our data suggests that over expression of p53 and c-erbB-2 is associated with malignant progression of molar pregnancy. We encountered that high expression of p53 and c-erbB-2 in trophoblastic cells could predict gestational trophoblastic neoplasia during the early stages.

Keywords: C-erbB-2; Complete Hydatiform Mole; P53; Prognosis.

Figure 1.. Hydropic Villi with Trophoblastic Proliferation and Their Diffuse Nuclear Immunoreactivity for P53 (× 40)

(A), Nuclear cytotrophoblasts and syncytiotrophoblasts immunoreactivity (× 100) (B), Negative immunoreactivity of syncytiotrophoblasts and positive nuclear immunoreactivity of more than 80% of trophoblasts (C), positive cytoplasmic immunoreactivity of trophoblasts for c-erbB-2 with fairly no staining of syncytiotrophoblasts (D), Hydropic villi with trophoblastic vacuolization and positive immunoreactivity in about 80% of trophoblasts (× 40)(E), (× 100) (F).

Figure 2.. Depicts the ROC Curve to Determine a Cut Off Value for Percentage of Cells with Positive Immunostaining

For p53 and c-erbB-2 markers among cytotrophoblasts and syncytiotrophoblasts in molar tissue to estimate their risk to GTN transformation.The test result variable(s): p53Cyto, p53Syncyto, Her2cyto, Her2Syncyto has at least one tie between the positive actual state group and the negative actual state group. Statistics may be biased. a, Under the nonparametric assumption. b, Null hypothesis, true area = 0.5.