Clear cell endometrial carcinoma and the TCGA classification

et al. 2021

Cancers

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113

126

Endometrial carcinoma represents the most common gynecological cancer in Europe and the USA. Histopathological classification based on tumor morphology and tumor grade has played a crucial role in the management of endometrial carcinoma, allowing a prognostic stratification into distinct risk categories, and guiding surgical and adjuvant therapy. In 2013, The Cancer Genome Atlas (TCGA) Research Network reported a large scale molecular analysis of 373 endometrial carcinomas which demonstrated four categories with distinct clinical, pathologic, and molecular features: POLE/ultramutated (7% of cases) microsatellite instability (MSI)/hypermutated (28%), copy-number low/endometrioid (39%), and copy-number high/serous-like (26%). In the present article, we report a detailed histological and molecular review of all endometrial carcinoma histotypes in light of the current ESGO/ESTRO/ESP guidelines. In particular, we focus on the distribution and prognostic value of the TCGA groups in each histotype.

Section: Clear Cell Carcinoma (Ccec)mentioning

confidence: 99%

New Pathological and Clinical Insights in Endometrial Cancer in View of the Updated ESGO/ESTRO/ESP Guidelines

Santoro

Angelico

et al. 2021

Cancers

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113

126

“…P53-wt group has good-to-intermediate prognosis, low mutational load, low somatic copy number alteration rate, and absence of a molecular signature; this group is identified by excluding molecular signatures of the other groups [2,3,6,8,9]. Given the differences in terms of molecular background, histologic characteristics and prognosis [17][18][19][20][21][22], these groups may be considered as different diseases within endometrial cancer landscape. These different entities might also have different pathogenesis and risk factors, and might occur in different phenotypes of patients.…”

Section: Introductionmentioning

confidence: 99%

Clinical features of ProMisE groups identify different phenotypes of patients with endometrial cancer

Raffone

Gabrielli

et al. 2021

Arch Gynecol Obstet

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Background The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) groups has identified four molecular prognostic groups of endometrial cancer (EC): POLE-mutated (POLE-mt), mismatch repair-deficient (MMR-d), p53-abnormal (p53-abn), p53-wild-type (p53-wt). These groups might have different pathogenesis and risk factors, and might occur in different phenotypes of patients. However, these data are still lacking. Objective To provide a clinical characterization of the ProMisE groups of EC. Methods A systematic review and meta-analysis was performed by searching seven electronic databases from their inception to December 2020, for all studies reporting clinical characteristics of EC patients in each ProMisE group. Pooled means of age and BMI and pooled prevalence of FIGO stage I and adjuvant treatment in each ProMisE group were calculated. Results Six studies with 1, 879 women were included in the systematic review. Pooled means (with standard error) and prevalence values were: in the MMR-d group, age = 66.5 ± 0.6; BMI = 30.6 ± 1.2; stage I = 72.6%; adjuvant treatment = 47.3%; in the POLE-mt group, age = 58.6 ± 2.7; BMI = 27.2 ± 0.9; stage I = 93.7%; adjuvant treatment = 53.6%; in the p53-wt group, age = 64.2 ± 1.9; BMI = 32.3 ± 1.4; stage I = 80.5%; adjuvant treatment = 45.3%; in the p53-abn group, age = 71.1 ± 0.5; BMI = 29.1 ± 0.5; stage I = 50.8%; adjuvant treatment = 64.4%. Conclusion The ProMisE groups identify different phenotypes of patients. The POLE-mt group included the youngest women, with the lower BMI and the highest prevalence of stage I. The p53-wt group included patients with the highest BMI. The p53-abn group included the oldest women, with the highest prevalence of adjuvant treatment and the lowest prevalence of stage I. The MMR-d group showed intermediate values among the ProMisE groups for all clinical features.

“…The risk of recurrence in each group of STUMP according to the Stanford parameters was calculated as the number of patients who recurred divided by the total number of patients, as previously described [32][33][34][35]. The Kaplan-Meier survival analysis for the recurrence-free survival was calculated for each group.…”

Section: Discussionmentioning

confidence: 99%

Stanford parameters stratify the risk of recurrence in gynecologic smooth muscle tumors of uncertain malignant potential

Raffone

Gencarelli

et al. 2021

APMIS

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Smooth muscle tumor of uncertain malignant potential (STUMP) is an ill‐defined category of neoplasms, which represent a diagnostic challenge. We aimed to assess whether the Stanford parameters, that is, high mitotic index (≥10/10HPF), significant atypia (moderate‐to‐severe), and coagulative tumor cell necrosis (CTCN), even when focal or ambiguous, may be used to stratify the risk of recurrence in gynecological smooth muscle tumor of uncertain malignant potential (STUMP). Electronic databases were searched from their inception to October 2019. All studies assessing the Stanford parameters in gynecological STUMP series were included. STUMPs were subdivided according to the presence of the three Stanford parameters: high mitotic index, significant atypia, and CTCN. A Kaplan–Meier survival analysis was performed for recurrence‐free survival; hazard ratio (HR) was calculated in each category. Fourteen studies with 219 STUMPs were included. In 15.5% of cases, none of the three Stanford parameters were present, with a recurrence risk of 5.9%; 2.7% of cases showed high mitotic index alone, with a recurrence risk of 0% (HR = not calculable); 43.8% of cases showed significant atypia alone, with a recurrence risk of 18.7% (HR = 3.3; p = 0.012); 26.5% of cases showed CTCN alone, with a recurrence risk of 17.2% (HR = 3.1; p = 0.029); and 11.4% of cases showed at least two Stanford parameters, with a recurrence risk of 32% (HR = 7.5; p = 0.003). Stanford parameters may stratify the risk of recurrence of STUMP. Significant atypia and CTCN, but not high mitotic index, may be stand‐alone risk factors for recurrence in STUMP. The presence of at least two Stanford parameters, even if equivocal (e.g., uncertain or focal CTCN, focal significant atypia, mitotic index around 10/10HPF), might still be enough to support a diagnosis of leiomyosarcoma. Further studies are necessary in this field.