Expression of Pro-Apoptotic Bax and Anti-Apoptotic Bcl-2 Proteins in Hydatidiform Moles and Placentas With Hydropic Changes

Abstract- Morphologic examination still forms the main diagnostic tool in the differential diagnosis of molar placentas. However the criteria are subjective and show considerable inter-observer variability among pathologists. The aim of the present study was to investigate the role of Bcl-2 and Bax immunostaining in the differential diagnosis of molar placentas. Bax and Bcl-2 immunohistochemical staining were performed in 19 molars (8 partial and 11 complete hydatidiform mole) and 10 non-molar (hydropic abortion) formalin-fixed, paraffin-embedded tissue samples. Ploidy analysis using flow cytometry had confirmed diploidy in hydropic abortions and complete hydatidiform moles and triploidy in partial hydatidiform moles. Bcl-2 expression was observed only in syncytiotrophoblasts, No immunoreactivity was detected in Cytotrophoblasts, and stromal cells, the total score averages of Bcl-2 immunoexpression in partial hydatidiform moles and hydropic abortions were significantly higher than in complete hydatidiform moles, whereas no significant difference was observed between partial hydatidiform moles and hydropic abortions. Bax immunoreactivity was observed in cytotrophoblasts, stromal cells and occasionally in syncytiotrophoblasts. No statistically significant difference in Bax immunoexpression total score was observed among various groups. Based on the results of this study, Bcl-2 immunostaining offers a potential adjunctive diagnostic tool to distinguish complete hydatidiform mole from partial hydatidiform mole and hydropic abortion, but not partial hydatidiform mole from hydropic abortion, Bax immunostaining cannot be helpful in this regard.

[1]  A. Heidari,et al.  Expression of p53 Protein in Colorectal Cancer and Association With Prognostic Factors in Northeast Iran , 2018 .

[2]  A. Derbent,et al.  Immunohistochemical Analysis of E-Cadherin, p53 and Inhibin-α Expression in Hydatidiform Mole and Hydropic Abortion , 2016, Pathology & Oncology Research.

[3]  L. Sunde,et al.  Gestational trophoblastic diseases - clinical guidelines for diagnosis, treatment, follow-up, and counselling. , 2015, Danish medical journal.

[4]  T. Wargasetia,et al.  Characterization of apoptosis and autophagy through Bcl-2 and Beclin-1 immunoexpression in gestational trophoblastic disease , 2015, Iranian journal of reproductive medicine.

[5]  K. Murphy,et al.  Characteristics of hydatidiform moles: analysis of a prospective series with p57 immunohistochemistry and molecular genotyping , 2014, Modern Pathology.

[6]  N. Sebire,et al.  Gestational trophoblastic disease: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. , 2013, Annals of oncology : official journal of the European Society for Medical Oncology.

[7]  M. Mahmoudi,et al.  Detection of Sugar Chain Expression in Hydatidiform Mole Using Lectin Histochemistry , 2013, Iranian Red Crescent medical journal.

[8]  R. Berkowitz,et al.  Current advances in the management of gestational trophoblastic disease. , 2013, Gynecologic oncology.

[9]  J. Picard,et al.  Altered p16 and Bcl-2 Expression Reflects Pathologic Development in Hydatidiform Moles and Choriocarcinoma , 2013, Pathology & Oncology Research.

[10]  R. Kurman,et al.  Diagnostic Reproducibility of Hydatidiform Moles: Ancillary Techniques (p57 Immunohistochemistry and Molecular Genotyping) Improve Morphologic Diagnosis , 2012, The American journal of surgical pathology.

[11]  K. Murphy,et al.  Hydatidiform moles: ancillary techniques to refine diagnosis. , 2011, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[12]  G. Condous,et al.  Recognising gestational trophoblastic disease. , 2009, Best practice & research. Clinical obstetrics & gynaecology.

[13]  J. Soper.  Gestational trophoblastic disease. , 2006, Obstetrics and gynecology.

[14]  H. Katabuchi,et al.  Interobserver and Intraobserver Variability in the Diagnosis of Hydatidiform Mole , 2005, The American journal of surgical pathology.

[15]  N. Wake,et al.  Genetic origin and imprinting in hydatidiform moles. Comparison between DNA polymorphism analysis and immunoreactivity of p57KIP2. , 2005, The Journal of reproductive medicine.

[16]  D. Mutch,et al.  Diagnosis and treatment of gestational trophoblastic disease: ACOG Practice Bulletin No. 53. , 2004, Gynecologic oncology.

[17]  Neil J. Sebire,et al.  Diagnosis of gestational trophoblastic disease in early pregnancy , 2002 .

[18]  S. Tsao,et al.  Current understandings of the molecular genetics of gestational trophoblastic diseases. , 2002, Placenta.

[19]  I. Al-Bozom.  p53 and Bcl‐2 oncoprotein expression in placentas with hydropic changes and partial and complete moles , 2000, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[20]  H. Matsuo,et al.  Changes in proliferative potential, apoptosis and Bcl-2 protein expression in cytotrophoblasts and syncytiotrophoblast in human placenta over the course of pregnancy. , 2000, Endocrine journal.

[21]  S. Smith,et al.  Expression of BCL-2, BAX and BAK in the trophoblast layer of the term human placenta: a unique model of apoptosis within a syncytium. , 2000, Placenta.

[22]  J. Sandbank,et al.  Expression of the p53 gene and apoptosis in gestational trophoblastic disease. , 2000, Placenta.

[23]  H. Ngan,et al.  Apoptosis in gestational trophoblastic disease is correlated with clinical outcome and Bcl-2 expression but not Bax expression. , 1999, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[24]  T. Nikaido,et al.  Inverse relationship between apoptosis and Bcl-2 expression in syncytiotrophoblast and fibrin-type fibrinoid in early gestation. , 1999, Molecular human reproduction.

[25]  T. Nagasaka,et al.  p53, Bax and Bcl-2 expression, and apoptosis in gestational trophoblast of complete hydatidiform mole. , 1998, Placenta.

[26]  M. Castellucci,et al.  BCL-2 expression in the human placenta and its correlation with fibrin deposits. , 1998, Human reproduction.

[27]  R. Berkowitz,et al.  c-myc, c-erbB-2, c-fms and bcl-2 oncoproteins. Expression in normal placenta, partial and complete mole, and choriocarcinoma. , 1998, The Journal of reproductive medicine.

[28]  J. Chi,et al.  Patterns of bcl-2 expression in placenta. , 1995, Pathology, Research and Practice.

[29]  H Fox,et al.  Can histopathologists reliably diagnose molar pregnancy? , 1993, Journal of clinical pathology.

[30]  M. Fukunaga,et al.  Application of flow cytometry in diagnosis of hydatidiform moles. , 1993, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[31]  R. Berkowitz,et al.  Diagnosis and management of the primary hydatidiform mole. , 1988, Obstetrics and gynecology clinics of North America.

[32]  A. Lilienfeld,et al.  Inter‐ and Intra‐Pathologist Variability in the Diagnosis of Gestational Trophoblastic Neoplasia , 1987, Obstetrics and gynecology.