HER2-positive Endometrial Cancer Subtype Carries Poor Prognosis

Overview

Journal Clin Transl Sci

Specialties Biomedical Engineering
General Medicine

Date 2014 Sep 10

PMID 25201050

Citations 12

Authors

Sylwia Lapinska-Szumczyk

Anna Supernat

Hanna Majewska

Jacek Gulczynski

Agata Luczak

Wojciech Biernat

Dariusz Wydra

Anna J Zaczek

Affiliations

Soon will be listed here.

Abstract

Endometrial cancer (EC) is a hormone-dependent, most frequent malignancy of the female genital tract, yet no molecular subtype classification based receptor status (estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor 2 [HER2]) has been established so far. Assuming that molecular subtypes might differ fundamentally in EC, we analyzed expression levels of ER, PR, and HER2 with immunohistochemistry and aimed to determine clinical significance of four molecular subtypes: ER+/PR+/HER2+; ER+/PR+/HER2-, ER-/PR-/HER2+, and ER-/PR-/HER2-. The study included 400 formalin-fixed paraffin-embedded primary tumor EC samples which covered all stages of endometrial carcinoma, from IA to IVB. ER-/PR-/HER2+ subtype correlated with the poorest outcome, ER+/PR+/HER2- subtype was associated with the most favorable prognosis (p = 0.002). Molecular subtype division remained an independent prognostic factor in multivariate analysis, accompanying parameters such as diabetes, hypertension, stage, myometrial infiltration, and metastases, all of which yielded hazard ratios between 1.39 and 2.23. ER+/PR+/HER2+ and ER+/PR+/HER2- subtypes had low average TP53 and TOP2A expression levels when compared with ER-/PR-/HER2+ and ER-/PR-/HER2- (both p < 0.00001). Molecular subtypes in EC do show diversity in terms of prognosis, clinicopathological, and molecular characteristics. ER-/PR-/HER2+ subtype exhibit is exceptionally aggressive tumor characteristics. Subtype differentiation might aid prediction of treatment response in EC.

Citing Articles

A phase 2 trial of zanidatamab in HER2-overexpressed advanced endometrial carcinoma and carcinosarcoma (ZW25-IST-2).

Lumish M, Chui M, Zhou Q, Iasonos A, Sarasohn D, Cohen S Gynecol Oncol. 2024; 182:75-81.

PMID: 38262242 PMC: 11264355. DOI: 10.1016/j.ygyno.2023.12.028.

Significance of Mutational Status-Associated Signature in the Progression and Prognosis of Endometrial Carcinoma.

Chen Y, Zhao W, Bi F, Pan X, Yin L, Zhao C Oxid Med Cell Longev. 2022; 2022:1817339.

PMID: 35847579 PMC: 9280614. DOI: 10.1155/2022/1817339.

Prognostic molecular biomarkers in endometrial cancer: A review.

Hernandez J, Gonzalez-Montiel A, Allos-Villalva J, Cantu D, Barquet S, Olivares-Mundo A J Cancer Res Ther (Manch). 2021; 7(3):17-28.

PMID: 34322276 PMC: 8315102. DOI: 10.14312/2052-4994.2019-3.

A study of HER2 expression in endometrial carcinoma: a single centre experience.

Hashim M, Tizen N, Alfian N, Hashim H, Mohammed Nawi A, Md Pauzi S Pan Afr Med J. 2021; 38:200.

PMID: 33995806 PMC: 8106774. DOI: 10.11604/pamj.2021.38.200.19978.

Detection of ERBB2 amplification in uterine serous carcinoma by next-generation sequencing: an approach highly concordant with standard assays.

Robinson C, Harrison B, Ligon A, Dong F, Maffeis V, Matulonis U Mod Pathol. 2020; 34(3):603-612.

PMID: 33077919 DOI: 10.1038/s41379-020-00695-5.

References

. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004; 363(9403):157-63. DOI: 10.1016/S0140-6736(03)15268-3. View

Colombo N, Preti E, Landoni F, Carinelli S, Colombo A, Marini C . Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2011; 22 Suppl 6:vi35-9. DOI: 10.1093/annonc/mdr374. View

Trovik J, Wik E, Werner H, Krakstad C, Helland H, Vandenput I . Hormone receptor loss in endometrial carcinoma curettage predicts lymph node metastasis and poor outcome in prospective multicentre trial. Eur J Cancer. 2013; 49(16):3431-41. DOI: 10.1016/j.ejca.2013.06.016. View

Kothari R, Morrison C, Richardson D, Seward S, OMalley D, Copeland L . The prognostic significance of the triple negative phenotype in endometrial cancer. Gynecol Oncol. 2010; 118(2):172-5. DOI: 10.1016/j.ygyno.2010.04.015. View

Metzger-Filho O, Sun Z, Viale G, Price K, Crivellari D, Snyder R . Patterns of Recurrence and outcome according to breast cancer subtypes in lymph node-negative disease: results from international breast cancer study group trials VIII and IX. J Clin Oncol. 2013; 31(25):3083-90. PMC: 3753700. DOI: 10.1200/JCO.2012.46.1574. View

Sarode V, Han J, Morris D, Peng Y, Rao R . A Comparative Analysis of Biomarker Expression and Molecular Subtypes of Pure Ductal Carcinoma In Situ and Invasive Breast Carcinoma by Image Analysis: Relationship of the Subtypes with Histologic Grade, Ki67, p53 Overexpression, and DNA Ploidy. Int J Breast Cancer. 2012; 2011:217060. PMC: 3262571. DOI: 10.4061/2011/217060. View

Cheang M, Chia S, Voduc D, Gao D, Leung S, Snider J . Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009; 101(10):736-50. PMC: 2684553. DOI: 10.1093/jnci/djp082. View

Matias-Guiu X, Prat J . Molecular pathology of endometrial carcinoma. Histopathology. 2012; 62(1):111-23. DOI: 10.1111/his.12053. View

Goldhirsch A, Wood W, Coates A, Gelber R, Thurlimann B, Senn H . Strategies for subtypes--dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol. 2011; 22(8):1736-47. PMC: 3144634. DOI: 10.1093/annonc/mdr304. View

10.

Sho T, Hachisuga T, Nguyen T, Urabe R, Kurita T, Kagami S . Expression of estrogen receptor-α as a prognostic factor in patients with uterine serous carcinoma. Int J Gynecol Cancer. 2013; 24(1):102-6. DOI: 10.1097/IGC.0000000000000029. View

11.

Knezevic Stromar I, Jakic-Razumovic J . The value of immunohistochemical determination of topoisomerase IIα and Ki67 as markers of cell proliferation and malignant transformation in colonic mucosa. Appl Immunohistochem Mol Morphol. 2013; 22(7):524-9. DOI: 10.1097/PAI.0b013e3182a1c9c6. View

12.

Pecorelli S . Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet. 2009; 105(2):103-4. DOI: 10.1016/j.ijgo.2009.02.012. View

13.

Togami S, Sasajima Y, Oi T, Ishikawa M, Onda T, Ikeda S . Clinicopathological and prognostic impact of human epidermal growth factor receptor type 2 (HER2) and hormone receptor expression in uterine papillary serous carcinoma. Cancer Sci. 2012; 103(5):926-32. PMC: 7659356. DOI: 10.1111/j.1349-7006.2012.02240.x. View

14.

. Comprehensive molecular portraits of human breast tumours. Nature. 2012; 490(7418):61-70. PMC: 3465532. DOI: 10.1038/nature11412. View

15.

Perou C, Sorlie T, Eisen M, van de Rijn M, Jeffrey S, Rees C . Molecular portraits of human breast tumours. Nature. 2000; 406(6797):747-52. DOI: 10.1038/35021093. View

16.

Jiang X, Tang Q, Shen X, Li H, Chen L, Wang X . Tumor-associated macrophages, epidermal growth factor receptor correlated with the triple negative phenotype in endometrial endometrioid adenocarcinoma. Pathol Res Pract. 2012; 208(12):730-5. DOI: 10.1016/j.prp.2012.09.011. View

17.

Mrklic I, Pogorelic Z, capkun V, Tomic S . Expression of topoisomerase II-α in triple negative breast cancer. Appl Immunohistochem Mol Morphol. 2013; 22(3):182-7. DOI: 10.1097/PAI.0b013e3182910967. View

18.

Lan J, Huang H, Lee S, Chen T, Tai H, Hsu H . TOP2A overexpression as a poor prognostic factor in patients with nasopharyngeal carcinoma. Tumour Biol. 2013; 35(1):179-87. DOI: 10.1007/s13277-013-1022-6. View

19.

Budczies J, Klauschen F, Sinn B, Gyorffy B, Schmitt W, Darb-Esfahani S . Cutoff Finder: a comprehensive and straightforward Web application enabling rapid biomarker cutoff optimization. PLoS One. 2012; 7(12):e51862. PMC: 3522617. DOI: 10.1371/journal.pone.0051862. View

20.

Morrison D, Rahardja D, King E, Peng Y, Sarode V . Tumour biomarker expression relative to age and molecular subtypes of invasive breast cancer. Br J Cancer. 2012; 107(2):382-7. PMC: 3394967. DOI: 10.1038/bjc.2012.219. View