Faculty Collaboration Database

Expression patterns of mismatch repair proteins in cervical cancer uncover independent prognostic value of MSH-2. Int J Gynecol Cancer 2024 Jul 01;34(7):993-1000

Date

07/02/2024

Pubmed ID

38950928

Pubmed Central ID

PMC11228214

DOI

10.1136/ijgc-2024-005377

Scopus ID

2-s2.0-85197692726 (requires institutional sign-in at Scopus site)

Abstract

OBJECTIVE: Although early-detected cervical cancer is associated with good survival, the prognosis for late-stage disease is poor and treatment options are sparse. Mismatch repair deficiency (MMR-D) has surfaced as a predictor of prognosis and response to immune checkpoint inhibitor(s) in several cancer types, but its value in cervical cancer remains unclear. This study aimed to define the prevalence of MMR-D in cervical cancer and assess the prognostic value of MMR protein expression.

METHODS: Expression of the MMR proteins MLH-1, PMS-2, MSH-2, and MSH-6 was investigated by immunohistochemical staining in a prospectively collected cervical cancer cohort (n=508) with corresponding clinicopathological and follow-up data. Sections were scored as either loss or intact expression to define MMR-D, and by a staining index, based on staining intensity and area, evaluating the prognostic potential. RNA and whole exome sequencing data were available for 72 and 75 of the patients and were used for gene set enrichment and mutational analyses, respectively.

RESULTS: Five (1%) tumors were MMR-deficient, three of which were of neuroendocrine histology. MMR status did not predict survival (HR 1.93, p=0.17). MSH-2 low (n=48) was associated with poor survival (HR 1.94, p=0.02), also when adjusting for tumor stage, tumor type, and patient age (HR 2.06, p=0.013). MSH-2 low tumors had higher tumor mutational burden (p=0.003) and higher frequency of (frameshift) mutations in the double-strand break repair gene RAD50 (p<0.01).

CONCLUSION: MMR-D is rare in cervical cancer, yet low MSH-2 expression is an independent predictor of poor survival.

Author List

van den Berg MC, Berg HF, Stokowy T, Hoivik EA, Woie K, Engerud H, Ojesina AI, Haldorsen IS, Trovik J, Bertelsen BI, Krakstad C, Halle MK

Author

Akinyemi Ojesina MD, PhD Assistant Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
DNA Mismatch Repair
DNA-Binding Proteins
Female
Humans
Middle Aged
Mismatch Repair Endonuclease PMS2
MutL Protein Homolog 1
MutS Homolog 2 Protein
Prognosis
Uterine Cervical Neoplasms