P53 and MMR IHC assessment in D&C samples in patients with uterine cancer. Does it reliably capture their status compared to hysterectomy matched specimens analysis? Could early knowledge guide treatment decisions?

Author(s): John Syrios, Anastasios Christidis, Demetrios Tziortziotis, Antigoni Sourla, Dimitrios Mazis-Kourakos, Dimitrios Vlachos, Georgios Vlachos, Kyriakos Mitsakos-Barbayiannis

Purpose:

International guidelines strongly suggest assessment of POLe, MMR, p53 in patients with early stage endometrial cancer. MMR and p53 are commonly assessed with IHC after hysterectomy (+/-BSO). The main objective of this analysis is to test for the concordance of P53 and MMR status in D&C and hysterectomy matched samples, suggesting that a reliable determination in D&C samples may drive surgical treatment modalities and fertility sparing decision. A secondary objective of the analysis is to test whether there is association between the P53 or the MMR status at the D&C specimens with the depth of invasion or the LVSI status.

Methods:

In this single center study 73 matched D&C and hysterectomy samples in patients with clinically early stage endometrial cancer were collected and p53 and MMR status was assessed with IHC. Samples were obtained by gynaecologists and gynaecological oncologists and independently assessed by two expert in gynaecological oncology pathologists at REA hospital (Athens-Greece). Immunohistochemistry was performed using Ventana Benchmark Ultra. P53 was grouped in two mutually exclusive groups, that is mutant or wild type. Similarly, MMR status was grouped in two mutually exclusive groups, that is pMMR and dMMR To determine MMR status, sections were scored visually for loss or intact expression of the proteins MSH6, MSH2, MLH1 and PMS2.

Results:

There was a 100% accordance between p53 assessment in D&C and hysterectomy specimens. Discrepancy in MMR result was observed only in 1 case which stained negative for MLH1 in D&C but positive in hysterectomy, yielding an accordance of 98,6% between D&C and hysterectomy specimens. Absolute accordance in histology and grade characterization was observed in all matched specimens. No association was found between p53 and MMR status with LVSI and depth of myometrial invasion.

Conclusions:

p53 & MMR status can be accurately assessed with IHC in D&C samples. Repeat assessment after hysterectomy may not be necessary. Early knowledge of the molecular imprint of the disease on D&C samples may drive treatment decisions regarding surgical procedures, fertility preservation and further treatment plans.