Evidence map›Paper›PMID 40488817›Full record

ArticleInternational journal of urology : official journal of the Japanese Urological Association2025

Clinicopathological Characteristics of Upper Tract Urothelial Cancer With Loss of Immunohistochemical Expression of Mismatch Repair Proteins.

Go Kobayashi, Tetsutaro Hayashi, Yohei Sekino, Kenichiro Ikeda, Hikaru Nakahara, Kohei Kobatake, Keisuke Goto, Daiki Taniyama, Kazuya Kuraoka, Shintaro Akabane and 4 more

Abstract read
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In one paragraph

Article in International journal of urology : official journal of the Japanese Urological Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Go KobayashiLaboratory of Molecular Pathology, Department of Molecular Biosciences, Radiation Effects Research Foundation, Hiroshima, Japan.
Tetsutaro HayashiDepartment of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Yohei SekinoDepartment of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.ORCID https://orcid.org/0000-0003-1525-5463
Kenichiro IkedaDepartment of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Hikaru NakaharaDepartment of Clinical and Molecular Genetics, Hiroshima University Hospital, Hiroshima, Japan.
Kohei KobatakeDepartment of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.ORCID https://orcid.org/0000-0003-2098-3916
Keisuke GotoDepartment of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.ORCID https://orcid.org/0000-0002-3580-1401
Daiki TaniyamaDepartment of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Kazuya KuraokaDepartment of Diagnostic Pathology, Kure Medical Center and Chugoku Cancer Center, National Hospital Organization, Kure, Japan.
Shintaro AkabaneDepartment of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Hiroaki NiitsuDepartment of Clinical and Molecular Genetics, Hiroshima University Hospital, Hiroshima, Japan.
Takao HinoiDepartment of Clinical and Molecular Genetics, Hiroshima University Hospital, Hiroshima, Japan.
Kazuhiro SentaniDepartment of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Nobuyuki HinataDepartment of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.ORCID https://orcid.org/0000-0001-7014-6812

Funding

Japan Society for the Promotion of ScienceTakeda Science Foundation
6 · The paper itself

Abstract

objectivesLynch syndrome (LS) is an inherited cancer predisposition caused by germline mutations in DNA mismatch repair (MMR) genes. Upper tract urothelial carcinoma (UTUC) is the third most common cancer associated with LS. In this study, we examined MMR protein expression in UTUC using immunohistochemistry to clarify the clinicopathological characteristics and prognostic significance of LS-associated UTUC.

methodsWe analyzed the expression of MLH1, MSH2, MSH6, and PMS2 by immunohistochemistry in 118 cases of UTUC treated with radical nephroureterectomy. MMR deficiency was defined as tumors exhibiting less than 5% MMR protein expression. We conducted further investigations using public databases.

resultsMMR deficiency was identified in 15 (13%) of the 118 UTUC cases. These cases were associated with younger age, papillary morphology, low grade, low stage, low neutrophil-to-lymphocyte ratio, high levels of CD8-positive tumor-infiltrating lymphocytes, and favorable prognosis. Similar findings were observed through in silico analysis. Public datasets revealed that tumor mutational burden in UTUC was significantly higher in MMR-mutated cases compared to MMR-normal cases. A waterfall plot showed a high frequency of FGFR3 mutation in MMR-mutated cases in UTUC. Bioinformatics analysis using RNA-Seq datasets showed that MMR-mutated UTUC was associated with enriched gene sets for MYC targets v1 and oxidative phosphorylation. Furthermore, gene expression levels of GALNT12 and FRMD3 emerged as potential predictors of MMR mutation in UTUC.

conclusionsThese findings highlight the clinical value of evaluating MMR protein expression by immunohistochemistry, which could inform treatment strategies and surveillance protocols for UTUC patients.

Indexed as

Carcinoma, Transitional CellColorectal Neoplasms, Hereditary NonpolyposisDNA Mismatch RepairKidney NeoplasmsUreteral NeoplasmsAdultAgedAged, 80 and overBiomarkers, TumorDNA-Binding ProteinsFemaleHumansImmunohistochemistryLymphocytes, Tumor-InfiltratingMaleMiddle AgedBiomarkers, TumorDNA-Binding ProteinsG-T mismatch-binding proteinMismatch Repair Endonuclease PMS2MLH1 protein, humanMSH2 protein, humanMutL Protein Homolog 1MutS Homolog 2 ProteinPMS2 protein, humanclinicopathological significanceimmunohistochemistrylynch syndromemismatch repairupper tract urothelial carcinoma

Identifiers

PMID40488817
PMCPMC12410129

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.