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


Authors: Wagar, M. K.; Reetz, E.; Huang, D.; Kao, M. J.; Al-Niaimi, A. N.; Wallace, S. K.; Barroilhet, L. M.; McGregor, S. M.
Article Title: Patterns of primary metastasis and recurrence in mismatch repair deficiency and p53 abnormal endometrial carcinoma
Abstract: 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. © 2025 Elsevier Inc.
Keywords: immunohistochemistry; adult; cancer chemotherapy; controlled study; human tissue; aged; major clinical study; cancer recurrence; cancer adjuvant therapy; cancer radiotherapy; comparative study; cancer staging; follow up; antineoplastic agent; endometrium carcinoma; lymph node dissection; metastasis; tumor volume; pelvis lymphadenectomy; cohort analysis; retrospective study; protein p53; histology; in situ hybridization; mismatch repair; tissue microarray; carcinomatous peritonitis; regional metastasis; mismatch repair protein pms2; chemoradiotherapy; abdominal disease; para-aortic lymphadenectomy; human; female; article; mutl protein homolog 1; dna mismatch repair protein msh2; mismatched related donor
Journal Title: Gynecologic Oncology
Volume: 197
ISSN: 0090-8258
Publisher: Elsevier Inc.  
Date Published: 2025-06-01
Start Page: 171
End Page: 178
Language: English
DOI: 10.1016/j.ygyno.2025.05.004
PUBMED: 40359597
PROVIDER: scopus
DOI/URL:
Notes: Source: Scopus
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