Complementary role of p57kip2 immunostaining in diagnosing hydatidiform mole subtypes
-
Nurzaireena Zainal
,
Isa M. Rose
Abstract
Objectives
Gestational trophoblastic disease comprises of a spectrum of pregnancy-related tumours which includes complete (CHM) and partial hydatidiform moles (PHM). Accurate diagnosis and subclassification of HM subtypes are crucial as prognosis differs. Histopathological examination using haemotoxylin and eosin (H&E) staining remains the basis for diagnosing HM, with only 80% accuracy. p57kip2 is a cyclin-dependent kinase inhibitor (CDKI) protein and is strongly paternally imprinted, being expressed from maternal allele. Therefore, complete mole (CHM) with only paternal genome has nearly absent expression of p57kip2 compared to partial mole (PHM) having both paternal and maternal genomes. This study is aimed to determine usefulness of p57kip2 immunohistochemistry (IHC) analysis in the diagnosis of HM subtypes.
Methods
A total of 82 archived paraffin embedded HM tissues with subtypes classified based on H&E staining – 39 (47.5%) CHM, 41 (50.0%) PHM and two (2.43%) unclassified molar pregnancy were retrieved. All tissue samples were subjected for p57kip2 IHC analysis and HM subtypes were then reclassified.
Results
A total of 66 cases (80.5%) were re-classified as CHM, 14 cases (17.1%) as PHM and two cases (2.4%) were decidual and cystic tissues. Analysis using p57kip2 immunostaining showed a diagnostic discrepancy of 33.0% from routine H&E staining and helps to improve the characterisation of the HM subtypes specifically at early gestations which have less distinctive morphologies.
Conclusions
IHC using p57kip2 monoclonal antibody should be considered as a routine ancillary test to H&E in improving the diagnosis of HM subtypes particularly in developing countries with limited resources.
Funding source: Centre for Research and Instrumentation, Universiti Kebangsaan Malaysia
Award Identifier / Grant number: GGPM-2011-083, 2012
Acknowledgments
Assoc Prof Dr Nirmala Kampan was a recipient of Geran Galakan Penyelidik Muda (GGPM-2011-083) from Centre for Research and Instrumentation, Universiti Kebangsaan Malaysia. Study was done with technical support from medical technologist lab assistance in PPUKM and HKL.
-
Research funding: This research was funded by Centre for Research and Instrumentation, Universiti Kebangsaan Malaysia, GGPM-2011-083, 2012.
-
Author contributions: Concept and design: NZ., IR., NCK. MAJ., NHH. Development of methodology: NZ., AT., MAJ., NHH. Acquisition of data (acquired and managed patients, provided facilities, etc.): NZ., IR., NCK. RG., MNS, NHY., AT., MAJ., NHH. Analysis and interpretation of data (e.g., statistical analysis, computational analysis): NZ., IR., RG., AT., MAJ., NHH. Writing, review, and/or revision of the manuscript: NZ., IR., NCK. RG., MNS, NHY., AT., MAJ., NHH. Administrative, technical, or material support (i.e., organizing data, constructing databases): NZ., IR., RG., MNS, NHY., AT., MAJ., NHH. Study supervision: NCK., MAJ., NHH. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
-
Competing interests: Authors state no conflict of interest.
-
Informed consent: Informed consent was obtained from all individuals included in this study.
-
Ethical approval: This study was approved by Universiti Kebangsaan Malaysia Medical Centre (UKMMC) Ethics Committee and National Medical Research Registry (NMRR).
References
1. Loh, K, Sivalingam, N, Suryani, M. Gestational trophoblastic disease. Med J Malaysia 2004;59:697–702.Search in Google Scholar
2. Ngan, HY, Bender, H, Benedet, JL, Jones, H, Montruccoli, GC, Pecorelli, S. Gestational trophoblastic neoplasia, FIGO 2000 staging and classification. Int J Gynaecol Obstet 2003;83(1 Suppl):175–7. https://doi.org/10.1016/s0020-7292(03)90120-2.Search in Google Scholar
3. Bentley, RC. Pathology of gestational trophoblastic disease. Clin Obstet Gynecol 2003;46:513–22. https://doi.org/10.1097/00003081-200309000-00004.Search in Google Scholar
4. Steigrad, SJ. Epidemiology of gestational trophoblastic diseases. Best Pract Res Clin Obstet Gynaecol 2003;17:837–47. https://doi.org/10.1016/s1521-6934(03)00049-x.Search in Google Scholar
5. Nirmala, C, Nor Azlin, M, Harry, S, Lim, P, Shafiee, M, Nur Azurah, A, et al.. Outcome of molar pregnancies in Malaysia: a tertiary centre experience. J Obstet Gynaecol 2013;33:191–3. https://doi.org/10.3109/01443615.2012.741150.Search in Google Scholar
6. Levine, DA, Lin, L, Gaillard, S. Handbook for principles and practice of gynecologic oncology. Philadelphia, USA: Lippincott Williams & Wilkins; 2020.Search in Google Scholar
7. Matsui, H, Iitsuka, Y, Yamazawa, K, Tanaka, N, Seki, K, Sekiya, S. Changes in the incidence of molar pregnancies. A population‐based study in Chiba Prefecture and Japan between 1974 and 2000. Hum Reprod 2003;18:172–5. https://doi.org/10.1093/humrep/deg008.Search in Google Scholar
8. Matsuda, T, Wake, N. Genetics and molecular markers in gestational trophoblastic disease with special reference to their clinical application. Best Pract Res Clin Obstet Gynaecol 2003;17:827–36. https://doi.org/10.1016/s1521-6934(03)00096-8.Search in Google Scholar
9. Cheah, PL, Looi, LM, Sivanesaratnam, V. Hydatidiform molar pregnancy in Malaysian women: a histopathological study from the University Hospital, Kuala Lumpur. Malays J Pathol 1993;15:59.Search in Google Scholar
10. Khawajkie, Y, Mechtouf, N, Nguyen, NMP, Rahimi, K, Breguet, M, Arseneau, J, et al.. Comprehensive analysis of 204 sporadic hydatidiform moles: revisiting risk factors and their correlations with the molar genotypes. Mod Pathol 2020;33:880–92. https://doi.org/10.1038/s41379-019-0432-4.Search in Google Scholar
11. Paradinas, F. The diagnosis and prognosis of molar pregnancy: the experience of the National Referral Centre in London. Int J Gynecol Obstet 1998;60:S57–64. https://doi.org/10.1016/s0020-7292(98)80006-4.Search in Google Scholar
12. Gshwendtner, A, Neher, A, Kreczy, A, Muller-Holzner, E. DNA ploidy determination of early molar pregnancies by image analysis: comparison to histologic classification. Arch Pathol Lab Med 1998;122:1000.Search in Google Scholar
13. Berkowitz, RS, Goldstein, DP. Current management of gestational trophoblastic diseases. Gynecol Oncol 2009;112:654–62. https://doi.org/10.1016/j.ygyno.2008.09.005.Search in Google Scholar PubMed
14. Ronnett, BM. Hydatidiform moles: differential diagnosis, diagnostic reproducibility, genetics and ancillary techniques to refine diagnosis. Diagn Histopathol 2019;25:35–52. https://doi.org/10.1016/j.mpdhp.2018.12.003.Search in Google Scholar
15. Nguyen, NMP, Bolze, P-A, Slim, R. Hydatidiform moles. Textbook of autoinflammation. Switzerland: Springer Nature; 2019:485–97 pp.10.1007/978-3-319-98605-0_27Search in Google Scholar
16. Goldstein, DP, Berkowitz, RS, Horowitz, NS. Gestational trophoblastic disease. Abeloff’s clinical oncology. Philadelphia, USA: Elsevier; 2020:1544–59.e3 p.10.1016/B978-0-323-47674-4.00087-6Search in Google Scholar
17. Fukunaga, M. Flow cytometric and clinicopathologic study of complete hydatidiform moles with special reference to the significance of cytometric aneuploidy. Gynecol Oncol 2001;81:67–70. https://doi.org/10.1006/gyno.2000.6100.Search in Google Scholar PubMed
18. Usui, H, Sato, A, Ota, M, Ikeda, J-I, Shozu, M. Androgenetic complete hydatidiform moles with p57KIP2-positive immunostaining. Am J Clin Pathol 2020;154:776–83. https://doi.org/10.1093/ajcp/aqaa096.Search in Google Scholar PubMed
19. Osterheld, M, Caron, L, Chaubert, P, Meagher-Villemure, K. Combination of immunohistochemistry and ploidy analysis to assist histopathological diagnosis of molar diseases. Clin Med Pathol 2008;1:61–7. https://doi.org/10.4137/cpath.s601.Search in Google Scholar PubMed PubMed Central
20. Madi, J, Braga, A, Paganella, M, Litvin, I, Wendland, E. Accuracy of p57 KIP 2 compared with genotyping to diagnose complete hydatidiform mole: a systematic review and meta‐analysis. BJOG An Int J Obstet Gynaecol 2018;125:1226–33. https://doi.org/10.1111/1471-0528.15289.Search in Google Scholar PubMed PubMed Central
© 2021 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Original Articles
- Investigating the relationship between insulin resistance and adipose tissue in a randomized Tehrani population
- Antitumor effects of Auraptene in 4T1 tumor‐bearing Balb/c mice
- Voluntary exercise improves sperm parameters in high fat diet receiving rats through alteration in testicular oxidative stress, mir-34a/SIRT1/p53 and apoptosis
- Assessment of AXL and mTOR genes expression in medullary thyroid carcinoma (MTC) cell line in relation with over expression of miR-144 and miR-34a
- Is there a relation between serum methylarginine levels and infertility?
- Evaluation of Y chromosome microdeletions and chromosomal anomalies in infertile men
- Threshold values of antibodies to estrogen, progesteron and benzo [a] pyrene as a risk factor for the development of endometriosis
- Altered methylarginine levels after surgery in subjects with multinodular goiter
- Effects of eight weeks exercise training on serum levels of adropin in male volleyball players
- Urinary bisphenol A in women with polycystic ovary syndrome – a possible suppressive effect on steroidogenesis?
- Complementary role of p57kip2 immunostaining in diagnosing hydatidiform mole subtypes
- Short Communications
- Circulating Inhibitory Factor 1 levels in adult patients with Prader–Willi syndrome
- Determinants of serum adiponectin levels: a cross-sectional study
- Case Report
- Prophylactic gonadectomy in 46 XY females; why, where and when?
- Review Article
- Is the beta estradiol receptor receiving enough attention for its metabolic importance in postmenopause?
Articles in the same Issue
- Frontmatter
- Original Articles
- Investigating the relationship between insulin resistance and adipose tissue in a randomized Tehrani population
- Antitumor effects of Auraptene in 4T1 tumor‐bearing Balb/c mice
- Voluntary exercise improves sperm parameters in high fat diet receiving rats through alteration in testicular oxidative stress, mir-34a/SIRT1/p53 and apoptosis
- Assessment of AXL and mTOR genes expression in medullary thyroid carcinoma (MTC) cell line in relation with over expression of miR-144 and miR-34a
- Is there a relation between serum methylarginine levels and infertility?
- Evaluation of Y chromosome microdeletions and chromosomal anomalies in infertile men
- Threshold values of antibodies to estrogen, progesteron and benzo [a] pyrene as a risk factor for the development of endometriosis
- Altered methylarginine levels after surgery in subjects with multinodular goiter
- Effects of eight weeks exercise training on serum levels of adropin in male volleyball players
- Urinary bisphenol A in women with polycystic ovary syndrome – a possible suppressive effect on steroidogenesis?
- Complementary role of p57kip2 immunostaining in diagnosing hydatidiform mole subtypes
- Short Communications
- Circulating Inhibitory Factor 1 levels in adult patients with Prader–Willi syndrome
- Determinants of serum adiponectin levels: a cross-sectional study
- Case Report
- Prophylactic gonadectomy in 46 XY females; why, where and when?
- Review Article
- Is the beta estradiol receptor receiving enough attention for its metabolic importance in postmenopause?
