Immunohistochemical Profiles of Endometrioid Endometrial Carcinomas With and Without Metastatic Disease

Abstract

A minority of endometrial carcinomas present at an advanced stage with a poor prognosis, and should be identified to individualize treatment. Immunohistochemical markers have been studied, but most have not been directly linked to metastasis. This study analyzes the immunohistochemical profile of endometrioid endometrial carcinomas (EECs) with and without metastases, and corresponding metastases. Tissue microarray slides from stage I EECs, stage III-IV EECs, and corresponding metastases were stained and scored for expression of β-catenin, E-cadherin, ER, PR, PTEN, p16, MLH1, PMS2, L1CAM, p53, p21, and MIB1. Scores were compared between primary stage I and III-IV EECs, stage III-IV EECs, and the corresponding metastases, and between intra-abdominal and distant metastases. Primary tumors with distant metastases had a significantly lower ER expression than those without metastases or with intra-abdominal metastases. Distant metastases had a significantly lower PR expression than the corresponding primary tumor and intra-abdominal metastases. In contrast, p16 and PTEN expression was significantly higher in intra-abdominal metastases compared with corresponding primary tumors. Immunohistochemistry predicts both presence and location of EEC metastases. Loss of ER and PR was related to distant spread, and increased expression of PTEN and p16 was related to intra-abdominal spread. Additional research should assess the use of these markers in the diagnostic workup as well as the possibility to target metastases through these markers.

Immunohistochemical biomarkers are prognostic relevant in addition to the ESMO-ESGO-ESTRO risk classification in endometrial cancer

“…The percentage of L1CAM+ cases was slightly lower in our study compared with other studies [16,19,20,23,24]. This might be related to the fact that pre-operative analysis was used instead of final tumor sections in which L1CAM can be expressed focally and/or at the invasive front predominantly [25]. Our results are in line with a study reporting that patients with L1CAM+ had significantly reduced survival also in the ESMO-ESGO-ESTRO 'high and advanced/metastatic' risk group compared with normal L1CAM expression [24].…”

Added Value of Estrogen Receptor, Progesterone Receptor, and L1 Cell Adhesion Molecule Expression to Histology-Based Endometrial Carcinoma Recurrence Prediction Models: An ENITEC Collaboration Study

“…29 Interestingly, the expression of PR was shown to be lower in metastatic endometrial carcinoma lesions compared with the corresponding primary tumor, which suggests that loss of PR plays a role in EMT. 24,30 Expression of L1CAM has also been related to both distant spread and EMT, and these associations have been previously described, including in our previous paper on L1CAM. 14,15,31Y34 These studies show that expression of L1CAM is especially dependent on TGFA signaling and Wnt/A-catenin activity, both of which are inhibited by progesterone.…”

Mutational analysis of cervical cytology improves diagnosis of endometrial cancer: A prospective multicentre cohort study

“…The most frequently mutated genes included PTEN , ARID1A and PIK3CA . This is in line with previously reported frequencies between 37 and 61% for PTEN , 23 and 40% for ARID1A and 24 and 39% for PIK3CA in EC . POLE and TP53 were mutated in 12 and 31% of all cases.…”

“…This is in line with previously reported frequencies between 37 and 61% for PTEN, 23 and 40% for ARID1A and 24 and 39% for PIK3CA in EC. [22][23][24][25][26][27][28][29][30][31][32] POLE and TP53 were mutated in 12 and 31% of all cases. Earlier studies found similar frequencies for POLE (7-9.3%), and slightly lower rates of TP53-mutations (12.2-18%).…”