Dataset Information

MCM4 expression is associated with high-grade histology, tumor progression and poor prognosis in urothelial carcinoma.

ABSTRACT:

Background

We previously reported Minichromosome maintenance 4 (MCM4) overexpression in gastric cancer. However, the clinicopathological significance of MCM4 in urothelial carcinoma (UC) has not been investigated. To clarify the clinicopathological significance of MCM4 in UC, we investigated MCM4 expression with immunohistochemistry (IHC).

Methods

We analyzed the expression and distribution of MCM4 in 124 upper tract urothelial carcinoma (UTUC) samples by IHC. Additionally, using 108 urine samples, we analyzed MCM4 Immunocytochemistry (ICC) expression in urine cytology.

Results

In normal urothelium, MCM4 expression was weak or absent. Meanwhile, the strong nuclear expression of MCM4 was observed in UTUC tissues, and it was detected in 77 (62%) of a total of 124 UTUC cases. MCM4-positive UTUC cases were associated with nodular/flat morphology, high grade, high T stage, and poor prognosis. Moreover, MCM4 expression was significantly higher in the invasive front than in the tumor surface. Similar results were also obtained in TCGA bladder cancer cohort. Additionally, MCM4 expression was associated with high expression of Ki-67, HER2, EGFR, and p53 in UTUC. Among representative cancer-related molecules, MCM4 had an independent predictive value for progression-free survival and high-grade UC. ICC for MCM4 was also performed on urine cytology slides and showed that the nuclear expression of MCM4 was more frequently found in UC cells than in non-neoplastic cells. The diagnostic accuracy of urine cytology was improved by combining MCM4 immunostaining with cytology.

Conclusion

These results suggest that MCM4 might be a useful predictive biomarker for high-grade histology, tumor progression and poor prognosis in UC. Moreover, ICC for MCM4 might be helpful for UC detection as additional markers in the cytomorphology-based diagnosis.

SUBMITTER: Kobayashi G

PROVIDER: S-EPMC10515259 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MCM4 expression is associated with high-grade histology, tumor progression and poor prognosis in urothelial carcinoma.

Kobayashi Go G Hayashi Tetsutaro T Sentani Kazuhiro K Uraoka Naohiro N Fukui Takafumi T Kido Aya A Katsuya Narutaka N Ishikawa Akira A Babasaki Takashi T Sekino Yohei Y Nose Hiroyuki H Arihiro Koji K Hinata Nobuyuki N Oue Naohide N

Diagnostic pathology 20230922 1

<h4>Background</h4>We previously reported Minichromosome maintenance 4 (MCM4) overexpression in gastric cancer. However, the clinicopathological significance of MCM4 in urothelial carcinoma (UC) has not been investigated. To clarify the clinicopathological significance of MCM4 in UC, we investigated MCM4 expression with immunohistochemistry (IHC).<h4>Methods</h4>We analyzed the expression and distribution of MCM4 in 124 upper tract urothelial carcinoma (UTUC) samples by IHC. Additionally, using ...[more]

PMID: 37737200

Similar Datasets

Project description:A novel immune checkpoint, CD155/T-cell immunoreceptor with Ig and ITIM domains, has been recognized as a new therapeutic target in addition to conventional immune checkpoints, such as anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-L1), for urothelial carcinoma (UC). Fibroblast growth factor receptor (FGFR) is considered another new therapeutic target for UC. As FGFR3-mutant UC may be associated with decreased T-cell infiltration, FGFR3 inhibition may facilitate lymphocyte invasion into the tumor microenvironment. Although a combined effect of immune checkpoint inhibitors and FGFR inhibition is expected, the combined expression profiles of CD155, PD-L1 and FGFR3 have not been evaluated in upper tract UC (UTUC). The present study aimed to investigate the association between CD155 expression and clinicopathological factors in 208 patients with UTUC undergoing radical nephroureterectomy. Furthermore, the expression profiles of CD155, PD-L1 and FGFR3 were compared. Immunohistochemical analysis was performed using tissue microarray specimens and survival analyses were performed using the Kaplan-Meier method and the Cox proportional hazards model. High immunohistochemical expression of CD155 was observed in 177 patients (85.1%) and it was associated with advanced pathological stage and lymphovascular invasion. The survival rate was lower among patients with tumors exhibiting high CD155 expression than among those with tumors with low CD155 expression. In addition, multivariate survival analysis revealed that high CD155 expression was an independent prognostic factor for recurrence (hazard ratio=7.32, 95% CI=1.01-53.35, P=0.049). FGFR3 and immune checkpoint signaling molecules, such as CD155 and PD-L1, had a weak negative correlation. The present results indicated that the expression of CD155 is a useful marker for predicting the recurrence of UTUC. In addition, the immunohistochemical expression profiles of CD155, PD-L1 and FGFR3 may further the understanding of the role of FGFR-targeted therapies in immunotherapy for UTUC.

Dataset Information

MCM4 expression is associated with high-grade histology, tumor progression and poor prognosis in urothelial carcinoma.

Background

Methods

Results

Conclusion

Publications

MCM4 expression is associated with high-grade histology, tumor progression and poor prognosis in urothelial carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets