Immunohistochemical Staining: Prognostic Marker of Malignant Transformation of Hydatidiform Mole (HM)

Abstract

Background: The Gestational Trophoblastic Disease is a spectrum ranging from benign Hydatidiform mole to choriocarcinoma and is generally accompanied by a good prognosis. However, invasive behavior of the tissues in 10-20% of patients may lead to malignant transformation and metastasis. Early detection will be associated with less economic burden on the health system, and higher rates of favorable pregnancy outcomes in women with limited fertility window. Moreover, timely diagnosis may facilitate the appropriate recommendation of prophylactic chemotherapy in the high-risk group of GTN1. Therefore there is a need to find a predictive biomarker for diagnosis of the disease progression. Some Immunohistological (IHC) markers of prognostic significance are: p53, EGFR, HER2 NM23. This study tries to find association of these IHC markers for progression to GTN.

Objectives: To find prognostic markers of malignant transformation of hydatidiform mole (HM);And to find the outcome of Hydatiform moles in the cohort.

Material & methods: We followed up a cohort of 30-women following evacuation of molar pregnancy on post molar follow up from Jan 2016 to Dec 2020. The IHC of the molar tissues obtained from these patients were evaluated for expression of p53, EGFR, HER2, and Nm23. They were prospectively followed with beta hCG as marker for development of GTN as routine till beta hCG showed normal/Abnormal regression. Those who developed GTN were scored using Figo Prognostic score and given chemotherapy as per protocol.

Results: 27 cases of HM were studied.19 were CHM and 8 were PM. 3 patient's IHC could not be done due to inadequate tissue. Age of women ranged from 18-40 years. P53 expression is seen more on surface trophoblast as compared to synchiotrpoblst p = 0.02 in patients who developed GTN Grade 3. EGFR - Immunostaining : Minimal staining of synchio and cytotrophoblast in patients with GTN grade 1 (p = 0.10). Her 2 strong membrane positivity for extravillous trophoblasts in contrast to weak reaction on surface trophoblasts grade 2 (p = 0.05). NM23 Increased staining in those with normal beta hCG regression grade 4 (p < 0.0001) those who did not develop GTN, Five patients developed GTN on follow up. 4 were stage 1 Figo score <6 and 1 case was Stage II Figo score low risk <6. All were given single agent chemotherapy with either Methotrexate or Actinomycin D. All responded to Single agent chemotherapy and went into remission. 3 cases were treated with methotrexate (1 case responded with 2 cycles and 2 with 6 cycles) Actinomycin D (2 cases response with 7 & 14 cycles respectively). None of the patients receiving Methotrexate developed side effects but those 2 patients who received Actinomycin D had vomiting, oral ulcers and alopecia.

Conclusion: Overexpression of P53 might be considered a potential biomarker to predict the progression of GTD toward malignancy. Overexpression of NM23 has high sensitivity of molar regression. Hence all molar tissues need to be studied for p53 and NM23 IHC Markers. NM23 has highest negative predictive value.

Supplementary information: The online version contains supplementary material available at 10.1007/s13224-024-02002-7.

Keywords: GTN; Hydatidiform mole; Immunohistochemical markers.