Background: Endometrial undifferentiated/dedifferentiated carcinoma (UDC/DDC) is a recently described aggressive variant of endometrial carcinoma, which shows mismatch repair (MMR) deficiency in about half of cases. Aim: To assess whether MMR-deficient UDC/DDC have distinct clinico-pathological features. Materials and methods: A systematic review and meta-analysis was performed by searching 4 electronic databases from their inception to October 2020 for all studies reporting clinicopathological characteristics of UDC/DDC series. Student t-test (for continuous variables), Cox regression analysis (for overall survival) and odds ratio (OR, for dichotomous variables) were used with a significant p-value < 0.05; data were pooled by using a random effect model. Results: Twelve studies were included. MMR-deficiency was significantly associated with older age (p = 0.024), p53-wild-type (p = 0.005), ARID1A loss (p = 0.001) and PD-L1 expression (p = 0.019), but not with overall survival (p = 0.307), extension beyond corpus (p = 0.787) or beyond uterus (p = 0.403), presence of a differentiated component (p = 0.461), loss of expression of cytokeratins (p = 0.698), EMA (p = 0.309), estrogen receptor (p = 0.605), PAX8 (p = 0.959), SMARCA4/BRG1 (p = 0.321), SMARCB1/INI1 (p = 0.225) or claudin-4 (p = 0.094), or POLE exonuclease domain mutation p = (0.773). Conclusions: In UDC/DDC, MMR-deficiency appears associated with older age, p53-wild type and ARID1A loss, suggesting the possibility of a distinct pathway underlying dedifferentiation; the association with PD-L1 expression is attributable to the high mutational load and may have therapeutic implications. On the other hand, MMR-deficiency appears not to be associated with prognosis, stage, loss of differentiation markers or POLE mutation.

Clinico-pathological features associated with mismatch repair deficiency in endometrial undifferentiated/dedifferentiated carcinoma: A systematic review and meta-analysis

Mollo A.;Zullo F.;
2021

Abstract

Background: Endometrial undifferentiated/dedifferentiated carcinoma (UDC/DDC) is a recently described aggressive variant of endometrial carcinoma, which shows mismatch repair (MMR) deficiency in about half of cases. Aim: To assess whether MMR-deficient UDC/DDC have distinct clinico-pathological features. Materials and methods: A systematic review and meta-analysis was performed by searching 4 electronic databases from their inception to October 2020 for all studies reporting clinicopathological characteristics of UDC/DDC series. Student t-test (for continuous variables), Cox regression analysis (for overall survival) and odds ratio (OR, for dichotomous variables) were used with a significant p-value < 0.05; data were pooled by using a random effect model. Results: Twelve studies were included. MMR-deficiency was significantly associated with older age (p = 0.024), p53-wild-type (p = 0.005), ARID1A loss (p = 0.001) and PD-L1 expression (p = 0.019), but not with overall survival (p = 0.307), extension beyond corpus (p = 0.787) or beyond uterus (p = 0.403), presence of a differentiated component (p = 0.461), loss of expression of cytokeratins (p = 0.698), EMA (p = 0.309), estrogen receptor (p = 0.605), PAX8 (p = 0.959), SMARCA4/BRG1 (p = 0.321), SMARCB1/INI1 (p = 0.225) or claudin-4 (p = 0.094), or POLE exonuclease domain mutation p = (0.773). Conclusions: In UDC/DDC, MMR-deficiency appears associated with older age, p53-wild type and ARID1A loss, suggesting the possibility of a distinct pathway underlying dedifferentiation; the association with PD-L1 expression is attributable to the high mutational load and may have therapeutic implications. On the other hand, MMR-deficiency appears not to be associated with prognosis, stage, loss of differentiation markers or POLE mutation.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11386/4766682
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 11
  • ???jsp.display-item.citation.isi??? 7
social impact