A STUDY OF p57KIP2 EXPRESSION AND MORPHOLOGICAL FINDINGS OF COMPLETE AND PARTIAL HYDATIDIFORM MOLES.
Background: Hydatidiform mole (HM) is classified as complete and partial hydatidiform mole. The incidence of molar pregnancy demonstrated marked geographic and ethnic differences. The diagnosis is based on histopathology, karyotyping and flow cytometry. Objective of the present study was the diffe-rentiation and comparison between complete and partial hydatidiform mole on the basis of p57KIP2 ex-pression. This comparative study was conducted in the Department of Pathology, Postgraduate Medical Institute / Lahore General Hospital, Lahore from 1st Jan 2011 to 31st Dec 2013.
Methods: The case records of all the molar pregnancy specimens during study period were analyzed regarding patient's history, clinical examination, morphological features and p57KIP2 expression. The main outcome measures included morphological features and immunohistochemical p57KIP2 expres-sion.
Results: There were total of 50 cases which included 15 cases of complete and 35 cases of partial hyda-tidiform mole on H and E staining which proved to be 17 cases of complete and 33 cases of partial mole on p57KIP2 immunohistochemical expression. The commonest age of presentation of HM was 30 39 years.
Conclusion: Morphological findings of CHM differ from PHM on the basis of histopathological criteria. Complete hydatidiform mole showed absent expression and partial mole showed positive expression of p57KIP2 immunohistochemical staining. Thus p57KIP2 is a valuable diagnostic tool that could be used to differentiate complete and partial hydatidiform mole.
Keywords: Gestational trophoblastic disease, Hydatidiform mole, P57KIP2 IHC.
Gestational trophoblastic diseases are a spectrum of related disorders which consist of benign trophoblastic lesions, premalignant hydatidiform moles, and neopla-stic diseases.1 The incidence of molar pregnancy is in-creasing in South East Asia ranges from 3.2 9.9 / 1000 gestation.2 The incidence of molar pregnancy de-monstrated marked geographic and ethnic differences. One possible reason for this great geographical variat-ion is differences in diet in the different parts of the world.3
The diagnosis of hydatidiform mole is very impor-tant because it has great potential to give rise to cho-riocarcinoma.4 The use of abdomino-pelvic ultrasound along with serial AY HCG is the best method for the prevention of morbidity and mortality of early pregna-ncy loss.5 There is significant overlap in the histolo-gical features between complete and partial hydatidi-form moles, resulting in considerable interobserver and intraobserver variability in the diagnosis.6 Histo-logical criteria for diagnosis of complete as well as par-tial hydatidiform moles were given by Szulman and Surti in 1978.7,8 The following features were graded:
(a) Trophoblastic hyperplasia.
(b) Cistern formation.
(c) Pseudoinclusions of trophoblast.
(d) Fetal vessels in villous stroma.
Routine molecular analysis is impractical and un-necessary, therefore immunohistochemistry is neces-sary to establish the correct diagnosis of molar pregna-ncy.9 p57KIP2 is a cyclin dependent kinase inhibitor, which is a tumor suppressor gene.10 It is located on chromosome 11p15.5 and predominantly is expressed from the maternal allele.11
Because p57KIP2 is paternally imprinted, and both the X chromosomes in complete moles are derived from the father, it is expected that reduced or absent expression of p57KIP2 protein is seen in complete moles.12
PATIENTS AND METHODS
This comparative study was conducted at the Patho-logy Department of the Postgraduate Medical Institute from 1st Jan 2011 to 31st Dec 2013. There were 50 specimens of uterine curettings diagnosed as molar preg-nancy. All patients having molar pregnancy with eleva-ted AY-HCG (human chorionic gonadotropin), ultraso-nic or histopathological evidence of the disease were included in the study.
Patients with incomplete history and without AY-HCG levels were excluded. Normal placental tissue was used as positive control of p57KIP2 marker and negative controls were prepared by omission of the primary antibody.
Positive reactivity was interpreted only when dis-tinct nuclear staining was identified. Cells with only cytoplasmic granular staining were regarded as neg-ative. The staining of equal or more than 10% of total cytotrophoblastic cells were presumed positive and results below of this threshold were considered as neg-ative. The data were statistically analyzed by using the Pearson's Chi-square test / Fisher exact test with SPSS software (SPSS-18).
There were total 50 specimens, among those 15 (30%) were found as complete and 35 (70%) were as partial hydatidiform moles on H and E staining but were found on IHC as CHM 17 (34%) and PHM 33 (66%) as shown in table 3.
P57KIP2 was strongly expressed in villous cytotro-phoblast and villous mesenchyme in 33 (66%) partial hydatidiform moles. In contrast, P57KIP2 expression in villous cytotrophoblast, villous stromal cells and ex-travillous trophoblast was absent or markedly decre-ased in 17 (34%) complete hydatidiform mole (Fig. 2 and Fig. 4).
Diagnostic statistics (sensitivity, specificity, posi-tive predictive value, negative predictive value and dia-gnostic accuracy) were applied to validate the diagno-sis of hydatidiform moles on HandE staining with immu-nostaining. The data were gathered on a structured questionnaire, which were subsequently statistically analyzed by using the Pearson's Chi-square test / Fish-er exact test with the latest version of the SPSS soft-ware (SPSS-18).
Table 1: Types of hydatidiform mole on H and E stain.
Complete hydatidiform mole###15###30
Partial hydatidiform mole###35###70
Above tests were used to compare the histopatho-logical findings in P57KIP2 positive and negative cases of complete and partial hydatidiform moles.
Final Test Results
Pless than 0.05 was taken as significant.
Table 2: Types of hydatidiform mole on IHC.
Complete hydatidiform mole###17###34
Partial hydatidiform mole###33###66
Table 3: Comparison of HandE stains with p57 KIP2 IHC results in HM.
###No. of Cases
###mole (IHC###mole (IHC
mole ( HandE)
A hydatidiform mole is a type of pregnancy in which the placenta has grape like vesicles. The exact inci-dence in Pakistan is not known but one study has reported it to be 0.68 / 1000 births.13 It has been reported that the highest incidence of molar pregnancy in Asia is generally due to low socioeconomic status and mal-nutrition.14
The present study aimed to evaluate those parameters which are commonly used for the differential diagnosis of these two conditions. Significant hyper-plasia of trophoblastic tissue is required for the diag-nosis of molar pregnancy. All of the above features in our study are consistent with those of criteria for diag-nosis of CHM and PHM given by Szulman and Surti (1978).7,8 Keeping in view of the limitations of morpho-logic assessment alone, use of immunohistochemistry is required to refine the diagnosis of molar pregnancy. The value of immunohistochemical analysis of p57-KIP2 expression for improving the diagnosis of hyda-tidiform moles has been demonstrated in a number of studies.15,16
In the present study, we found that p57KIP2 Im-munohistochemistry could be reliably interpreted and there was excellent agreement between observers. Im-munoreactivity for p57KIP2 in cytotrophoblasts of PHM was 95% in our study. This is comparable to the study by Fukunaga (2004) and Jun et al (2003).17,18 Thus p57KIP2 is a diagnostic tool that could be used to differentiate complete and partial hydatidiform mole. It is shown to be a highly specific and sensitive marker.
In the present study, the following conclusions are drawn:
1) Clinical findings of HM are similar to the western world. Bleeding P/V was the most common symp-tom.
2) Morphological findings of CHM differ from PHM on the basis of histological criteria as diffuse tro-phoblastic hyperplasia was seen in most cases of CHM while partial trophoblastic hyperplasia was seen in most cases of PHM on Hand E staining.
3) PHM showed absent expression of p57KIP2 Imm-unohistochemical staining.
4) Thus p57KIP2 is a valuable diagnostic tool that could be used to differentiate complete and partial hydatidiform mole.
The authors are grateful to the Gynecologist of Lahore General Hospital and the Principal of PGMI, Lahore.
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|Date:||Mar 31, 2015|
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