Patterns of primary metastasis and recurrence in mismatch repair deficiency and p53 abnormal endometrial carcinoma.

Objectives: Molecular classification of endometrial carcinoma(EC) provides relevant prognostication and is now being utilized to determine adjuvant therapy. It is currently unclear how molecular classification relates to disease dissemination and recurrence patterns in EC. The objective of this study was to characterize patterns of disease in mismatch repair-deficient (MMRd) and p53 abnormal (p53abn) carcinomas.

Methods: Immunohistochemistry molecular classification was performed to relate patterns of disease spread among EC patients undergoing surgical staging/cytoreduction. Dissemination patterns were assigned according to the most distant site of disease and subdivided as carcinomatosis, visceral organ, or lymphatic locations. Standard statistical methods were employed for comparisons, including multivariate logistic regression.

Results: Of 380 cases, 127 had advanced disease at presentation: 43.4 % pelvic, 44.8 % lower abdominal, 7.1 % upper abdominal and 4.7 % extra-abdominal. P53abn carcinomas were more likely to present with peritoneal-based disease compared to MMRd and p53wt tumors(30.8 %, 11.7 %, and 9.7 %, p < 0.0001). Among 128 patients with recurrence, upper abdominal spread and carcinomatosis were more common with p53abn than MMRd or p53wt tumors(49.2 %, 10 %, 8.2 %, p < 0.0001 and 60.8 %, 7.5 %, 18.9 %, p < 0.0001). MMRd tumors were associated with lymphatic recurrences compared to p53abn or p53wt(55 %, 19.6 %, 35.1 %, p = 0.001). These associations remained significant in multivariate analysis.

Conclusions: EC recurrence patterns differ based on molecular classification. Patients with p53abn cancers are more likely to present with peritoneal-based disease and experience peritoneal recurrence. Patients with MMRd cancers are more likely to experience lymphatic-based recurrences. This information provides a model of biologic behavior of molecular subtypes that can inform prospective surgical and therapeutic trials.