Investigator
Birmingham Womens Hospital
FIGO 2023 endometrial cancer staging system: recommendations for the UK
Role of the pathologist in assessing response to treatment of ovarian and endometrial cancers
Standardisation of pathological evaluation of tissue responses to therapy permits robust stratification of patient outcomes for management decisions and allows comparison of results across clinical trials. In gynaecological pathology there are two major areas where pathological assessment of treatment response is currently used to determine ongoing therapy. High‐grade serous carcinoma (HGSC) of tubo‐ovarian origin frequently presents as high‐stage disease and may be managed by neoadjuvant chemotherapy with debulking surgery. The chemotherapy response score (CRS) is a reproducible, validated three‐tiered morphological scoring system to assess the response of HGSC to treatment. Interobserver agreement is shown to be substantial following online training, and women with CRS3 have significantly improved progression‐free and overall survival. Low‐grade endometrioid endometrial cancer and atypical hyperplasia/endometrioid intraepithelial neoplasia may be managed by progestogenic therapy in women who wish to preserve fertility or for whom medical co‐morbidities preclude surgical management. The response to treatment is assessed histologically in successive endometrial biopsies. The histological parameters are well described, but the pathological classification of treatment response is still under development. Pathological assessment of the response to treatment is incorporated into clinical guidelines.
Clinicopathological and molecular characterisation of ‘multiple‐classifier’ endometrial carcinomas
AbstractEndometrial carcinoma (EC) molecular classification based on four molecular subclasses identified in The Cancer Genome Atlas (TCGA) has gained relevance in recent years due to its prognostic utility and potential to predict benefit from adjuvant treatment. While most ECs can be classified based on a single classifier (POLE exonuclease domain mutations – POLEmut, MMR deficiency – MMRd, p53 abnormal – p53abn), a small but clinically relevant group of tumours harbour more than one molecular classifying feature and are referred to as ‘multiple‐classifier’ ECs. We aimed to describe the clinicopathological and molecular features of multiple‐classifier ECs with abnormal p53 (p53abn). Within a cohort of 3518 molecularly profiled ECs, 107 (3%) tumours displayed p53abn in addition to another classifier(s), including 64 with MMRd (MMRd–p53abn), 31 with POLEmut (POLEmut–p53abn), and 12 with all three aberrations (MMRd–POLEmut–p53abn). MMRd–p53abn ECs and POLEmut–p53abn ECs were mostly grade 3 endometrioid ECs, early stage, and frequently showed morphological features characteristic of MMRd or POLEmut ECs. 18/28 (60%) MMRd–p53abn ECs and 7/15 (46.7%) POLEmut–p53abn ECs showed subclonal p53 overexpression, suggesting that TP53 mutation was a secondary event acquired during tumour progression. Hierarchical clustering of TCGA ECs by single nucleotide variant (SNV) type and somatic copy number alterations (SCNAs) revealed that MMRd–p53abn tumours mostly clustered with single‐classifier MMRd tumours (20/23) rather than single‐classifier p53abn tumours (3/23), while POLEmut–p53abn tumours mostly clustered with single‐classifier POLEmut tumours (12/13) and seldom with single‐classifier p53abn tumours (1/13) (both p ≤ 0.001, chi‐squared test). Finally, the clinical outcome of patients with MMRd–p53abn and POLEmut–p53abn ECs [stage I 5‐year recurrence‐free survival (RFS) of 92.2% and 94.1%, respectively] was significantly different from single‐classifier p53abn EC (stage I RFS 70.8%, p = 0.024 and p = 0.050, respectively). Our results support the classification of MMRd–p53abn EC as MMRd and POLEmut–p53abn EC as POLEmut. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
