Immunohistochemical analysis of c-erbB-2, Bcl-2, p53, p21WAF1/Cip1, p63 and Ki-67 expression in hydatidiform moles

Pathol Res Pract. 2019 Mar;215(3):446-452. doi: 10.1016/j.prp.2018.12.015. Epub 2018 Dec 12.

Abstract

Hydatidiform moles (HM) are characterized by an abnormal proliferating trophoblast with a potential for a malignant transformation. Similar to other human tumors, trophoblastic pathogenesis is likely a multistep process involving several molecular and genetic alterations. The study was performed to investigate the expression patterns of c-erbB-2 and Bcl-2 oncoproteins, p53, p21WAF1/CIP1 and p63 tumor suppressor proteins and Ki-67 cell proliferation marker in HM. We conducted a retrospective study of 220 gestational products, including 39 hydropic abortions (HA), 41 partial HM (PHM) and 140 complete HM (CHM). The expression of c-erbB-2, Bcl-2, p53, p21WAF1/CIP1, p63 and Ki-67 was investigated by immunohistochemistry on archival tissues. c-erbB-2 expression was observed in three PHM and 10 CHM. Bcl-2 immunostaining was significantly higher in PHM (61%) and CHM (70.7%) compared with HA (7.7%, p = 0.001 and p < 0.0001, respectively). p53 expression was stronger in CHM (73.6%) compared with PHM (24.4%, p < 0.0001) and HA (12.8%, p < 0.0001). p21WAF1/CIP1 staining was observed as well in molar and non-molar gestations (p > 0.05). p63 immunoexpression was significantly described in CHM (85.7%) and PHM (78%) compared with HA (10.2%, p < 0.0001 and p = 0.0001, respectively). Ki-67 was significantly expressed in CHM (72.1%) compared with HA (46.2%, p = 0.005). Altered expression of Bcl-2, p53, p63 and Ki-67 reflects the HM pathological development. Immunohistochemical analysis is beneficial to recognize the HM molecular and pathogenic mechanisms. Furthermore, it could serve as a useful adjunct to conventional methods for refining HM diagnosis.

Keywords: Bcl-2; Complete hydatidiform mole; Hydropic abortion; Ki-67; Partial hydatidiform mole; p53; p63.

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers, Tumor / analysis*
  • Cyclin-Dependent Kinase Inhibitor p21 / analysis
  • Cyclin-Dependent Kinase Inhibitor p21 / biosynthesis
  • Female
  • Humans
  • Hydatidiform Mole / metabolism
  • Hydatidiform Mole / pathology*
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Ki-67 Antigen / biosynthesis
  • Membrane Proteins / analysis
  • Membrane Proteins / biosynthesis
  • Middle Aged
  • Pregnancy
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Receptor, ErbB-2 / analysis
  • Receptor, ErbB-2 / biosynthesis
  • Retrospective Studies
  • Tumor Suppressor Protein p53 / analysis
  • Tumor Suppressor Protein p53 / biosynthesis
  • Uterine Neoplasms / metabolism
  • Uterine Neoplasms / pathology*
  • Young Adult

Substances

  • BCL2 protein, human
  • Biomarkers, Tumor
  • CDKN1A protein, human
  • CKAP4 protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Ki-67 Antigen
  • Membrane Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • ERBB2 protein, human
  • Receptor, ErbB-2