Challenges in diagnosing hydatidiform moles: a review of promising molecular biomarkers

ABSTRACT

Introduction

Hydatidiform moles (HMs) are pathologic conceptions with unique genetic bases and abnormal placental villous tissue. Overlapping ultrasonographical and histological manifestations of molar and non-molar (NM) gestations and HMs subtypes makes accurate diagnosis challenging. Currently, immunohistochemical analysis of p57 and molecular genotyping have greatly improved the diagnostic accuracy.

Areas covered

The differential expression of molecular biomarkers may be valuable for distinguishing among the subtypes of HMs and their mimics. Thus, biomarkers may be the key to refining HMs diagnosis. In this review, we summarize the current challenges in diagnosing HMs, and provide a critical overview of the recent literature about potential diagnostic biomarkers and their subclassifications. An online search on PubMed, Web of Science, and Google Scholar databases was conducted from the inception to 1 April 2022.

Expert opinion

The emerging biomarkers offer new possibilities to refine the diagnosis for HMs and pregnancy loss. Although the additional studies are required to be quantified and investigated in clinical trials to verify their diagnostic utility. It is important to explore, validate, and facilitate the wide adoption of newly developed biomarkers in the coming years.

KEYWORDS:

• Biomarkers
• diagnosis
• gestational trophoblastic diseases
• hydatidiform mole
• hydropic abortion

Article highlights

• It is important to distinguish HMs from NM gestations and to subclassify HMs since they are associated with varying patient management strategies and clinical prognoses.

• Overlapping ultrasonographical and histological manifestations of molar and NM gestations and HMs subtypes makes accurate diagnosis challenging.

• Ancillary techniques, including immunohistochemistry of p57 and short tandem repeat (STR) genotyping, have been utilized in routine practice but they still have limitations.

• Emerging new molecular biomarkers for HMs involved in genetics, immunity, tumorigenesis, etc. can be associated with HMs molecular mechanisms and biological behaviours. And they showed potential diagnostic application value.

• Newer molecular techniques and diagnostic biomarkers are urgently needed, especially for the differential diagnosis of partial hydatidiform moles (PHMs) and abortion and it is necessary to further quantified and investigated these new biomarkers in clinical trials to truly integrate them into routine clinical practice.

Acknowledgments

Figure 2 and Figure 3 were created with Biorender.com.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewers disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (82071665) and the Key Research and Development Program of Zhejiang Province, China (2020C03116).