Estrogen/Progesterone Receptor Loss, CTNNB1 and KRAS Mutations Are Associated With Local Recurrence or Distant Metastasis in Low-Grade Endometrial Endometrioid Carcinoma

Author:

Chibbar Rajni1ORCID,Foerstner Sabrina2,Suresh Janarathnee1,Chibbar Richa3,Piche Alexandre1,Kundapur Deeksha4,Kanthan Rani1,Kundapur Vijayanand4,Lee Cheng Han2,Agrawal Anita5,Lai Raymond2

Affiliation:

1. Department of Laboratory Medicine and Pathology, University of Saskatchewan, Saskatoon, SK

2. Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB

3. Department of Medicine, Lakeridge Health, Oshawa

4. Saskatchewan Cancer Agency, Saskatoon, SK, Canada

5. Department of Obstetrics and Gynecology, Queen’s University, Kingston, ON

Abstract

A subset of endometrial endometrioid carcinomas (EECs) with low-grade histology recur with poor outcomes. Published evidence suggests that poor outcomes may be associated with loss of expression of ER-alpha (ER-α) as well as with β-Catenin-1 (CTNNB1) and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. This study reports on institutional experience with the incidence of recurrence in low-grade EEC and their association with CTNNB1 and KRAS mutations as well as estrogen/progesterone receptor (ER/PR) expression. Forty-eight (8.5%) out of 568 cases of low-grade EEC with biopsy-proven recurrence were identified; and were analyzed by immunohistochemistry for ER, PR, p53, MMR protein, and mutation analysis for exon 3 of the CTNNB1 and exon 2 of KRAS in relation to recurrence type, local or distant metastasis/recurrence. Twenty-three patients (4%) developed local, and 25 patients (4.4%) developed distant metastases/recurrence. Decreased expression or loss of ER/PR was found in 17/44 (38.6%) patients with recurrence. Eighty-four percent of patients with low-grade EEC and local recurrence had CTNNB1 mutations. Seventy-three percent of patients with distant metastasis/recurrence had KRAS mutations. The association of these mutations with the type of recurrence was statistically significant for both. Five cases with the morphology of low-grade EEC were reclassified as mesonephric-like carcinoma and were universally characterized by distant metastasis/recurrence, loss of ER/PR expression, large tumor size, absence of CTNNB1 mutations, and the presence of KRAS mutations. In low-grade EEC, CTNNB1 and KRAS mutations are associated with local recurrence and distant metastasis/recurrence, respectively, suggesting that these 2 different progression types may be conditioned by tumor genotype. ER/PR immunohistochemistry may be helpful in identifying poor performers in low-grade EEC. Furthermore, identification of the decreased expression or loss of ER/PR in tumors with low-grade histology should prompt consideration of mesonephric-like carcinoma, which is a more aggressive tumor than the low-grade EEC. KRAS mutations were associated with distant metastasis/recurrence in tumors with and without mesonephric-like phenotype.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Medical Laboratory Technology,Histology,Pathology and Forensic Medicine

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