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LiFE re
Literature for ENYGO
Pathology in endometrial cancer (prognostic factors, EIN, EIC)
Editor Santiago Scasso
Descriptive summary
Within the period covered by the 3rd issue of LiFE report, the
ESMO-ESTRO-ESGO consensus was one of the most important
publications on endometrial cancer (EC).
The main recommendations of the “Prevention and scree-
ning” working group are as follows:
A typical hyperplasia (AH)/endometrial intraepithelial neoplasia
(EIN) is the preferred terminology of the precursor lesion of EC.
A H/EIN or grade 1 endometrioid endometrial cancer (EEC) must be
confirmed/diagnosed by expert pathologist.
M orphology (and not immunohistochemistry (IHC)) should be used
to distinguish AH/EIN from EEC.
S ometimes morphological criteria may be supported by IHC markers
and molecular alterations to distinguish from benign mimic lesions.
T he differential diagnosis of AH/EIN includes endometrial
hyperplasia without atypia, glandular and stromal breakdown,
focal glandular crowding, and epithelial metaplasia. Loss of PTEN
expression and loss of PAX-2 are the only IHC markers sufficiently
studied and recommended to use on curettage material.
IHC is not recommended to distinguish atypical polypoid adenomy-
oma (APA) from AH/EIN.
T he precursor of serous carcinoma, serous endometrial intraepitheli-
al carcinoma (SEIC), is considered a non-invasive cancer rather than
a precancer. Molecular alterations of serous carcinoma are already
present in SEIC. A completely negative immunoreactive pattern for
p53 is considered a surrogate for p53 mutation, and is present in
almost all SEIC and invasive serous carcinomas. Therefore, p53 by
IHC is recommended to distinguish SEIC from its mimics.
In selected cases in which cervical involvement may confuse the
origin of the uterine tumour, and considering that endocervical,
ovarian, and endometrial adenocarcinomas may show histopatho-
logical overlap, it is recommended to use a panel of markers
including at least ER, vimentin, CEA, and p16 by IHC. In addition,
HPV analysis can be considered.
W ilms tumour 1 gene by IHC is the recommended marker to deter-
mine the origin of serous cancer.
Continued on the next page 
International Journal of Gynecological Cancer, Volume 26, Supplement #1
ENDOMETRIAL CANCER
Other aspects to be highlighted in this literature review:
Lapinska-Szumczyk et al. analysed 400 formalin-fixed paraffin-em-
bedded primary tumour samples, and reported a molecular subtype
classification in EC, depending on the hormone receptor status
(Oestrogen Receptor-ER, Progesterone Receptor-PR) and Human
Epidermal growth factor Receptor 2 (HER2) analysed by IHC. Four
molecular subtypes are recognised and show diversity in terms of
prognosis, clinicopathological and molecular characteristics, with
ER+/PR+/HER2- and ER-/PR-/HER2+ groups exhibiting exceptionally
benign and aggressive behaviour, respectively. They have further
characterised the subtypes with the known pathways endometrial
carcinogenesis: PI3K-AKT pathway, TP53 system, and the mismatch
repair (MMR) mechanism. It is to emphasise that the molecular
subtype distinction, along with MMR and TP53 status, could become
a useful diagnostic tool for guiding individualised therapy.
Dudley et al. focused on the pathogenesis and prognostic value of
microsatellite instability (MSI) in EC in their review. MSI usually aris-
es from either germline mutations in components of the mismatch
repair (MMR) machinery (MSH2, MSH6, MLH1, PMS2) in patients
with Lynch syndrome (LS) or from somatic hypermethylation of the
MLH1 promoter. They reported significant responses of tumours with
MSI to immunotherapy anti-PD-1 inhibitors in patients who failed
conventional therapy. Authors concluded that MSI testing could
have an expanded role as a tool in the armamentarium of precision
medicine. 22 %-33 % is the estimated frequency of MSI in EC.
Shikama et al. suggest that analysing MMR status and searching
for Lynch syndrome may identify a subset of patients with higher
sensitivity to adjuvant therapies and favourable survival.
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