The Paris System for reporting urinary cytology improves the negative predictive value of high-grade urothelial carcinoma

Yamasaki, Mari; Taoka, Rikiya; Katakura, Kazuya; Matsunaga, Toru; Kani, Naoya; Honda, Tomoko; Harada, Satoshi; Tohi, Yoichiro; Matsuoka, Yuki; Kato, Takuma; Okazoe, Homare; Tsunemori, Hiroyuki; Ueda, Nobufumi; Haba, Reiji; Sugimoto, Mikio

doi:10.1186/s12894-022-01005-8

Cited by 16 publications

(22 citation statements)

References 18 publications

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“…Studies conducted by Goutas et al 20 . and Yamazaki et al 21 . both reported ROHM of 95% and 97.8%, respectively 20,21 …”

Section: Discussionmentioning

confidence: 96%

Are we on track for diagnosing high‐grade urothelial carcinoma with a minimum quantity of five malignant cells in lower tract specimens? Critical analysis of The Paris System Quantitation Criteria

Folarin,

Siddiqui

2023

Cancer Cytopathology

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BackgroundThe Paris System for Reporting Urinary Cytology (TPS) has gained universal acceptance as the standard for reporting urine cytology requiring at least 5–10 malignant cells to diagnose high‐grade urothelial carcinoma (HGUC) in lower and upper urinary tract specimens, respectively. These quantitation criteria are still subject to discussion, and this study specifically aims to validate the quantitation criterion of HGUC in lower urinary tract.DesignThe authors reviewed two cohorts of lower urinary tract cases. The first cohort consisted of 100 liquid‐based ThinPrep slides with the diagnosis of HGUC having positive histology on concurrent or follow‐up biopsies within 3 months. The second cohort was 36 HGUC cases with negative histology on concurrent biopsies and within 3 months. The number of high‐grade cells (HGCs) meeting the TPS qualitative criteria were counted under the light microscope driven in a grid‐like manner.ResultsThe first 100 urine samples showed five cases (5.0%) with three HGCs, three cases (3.0%) had four HGCs, five cases (5.0%) showed five HGCs, and 25 cases (25.0%) had between 6–10 HGCs. The risk of high‐grade malignancy (ROHM) in cases with five or more HGCs was 100%, whereas those with three HGCs was 60.0%. The second cohort of HGUC was considered “positive” despite a negative histology.ConclusionThis study confirms that quantitation is an essential key to diagnose HGUC. The current TPS criterion of a minimum of five malignant cells in lower tract is robust with a ROHM of 100%. Diagnosing HGUC with less than five HGCs runs the risk of lowering the ROHM.

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“…Studies conducted by Goutas et al 20 . and Yamazaki et al 21 . both reported ROHM of 95% and 97.8%, respectively 20,21 …”

Section: Discussionmentioning

confidence: 96%

Are we on track for diagnosing high‐grade urothelial carcinoma with a minimum quantity of five malignant cells in lower tract specimens? Critical analysis of The Paris System Quantitation Criteria

Folarin,

Siddiqui

2023

Cancer Cytopathology

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“…Clinically, as low grade UC has low malignant potential while high grade UC carries risk of disease progression, metastases and cause mortality, it is very important not to overlook high grade UC cases in particular [31][32][33]. Thus, there is a push to focus on diagnosing predominantly high grade UC in The Paris System [34,35].…”

Section: Discussionmentioning

confidence: 99%

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

Kobayashi

Hayashi

Sentani

et al. 2023

Preprint

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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 immunohistochemistry. Additionally, using 108 urine samples, we analyzed MCM4 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 highly 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. Immunocytochemistry (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.

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“…22,43 Although urine cytology is highly accurate for detecting HGUC, its sensitivity remains relatively low, even with TPS. 44,45 Thus, the presence of a predictive marker for HGUC, in addition to urine cytology, might be helpful in daily practice. The present study and Hinsch et al (2017) showed that the TUBB3 expression was significantly associated with HGUC.…”

Section: Discussionmentioning

confidence: 99%

“…Clinically, since HGUC can invade and cause death, there is a push to focus on diagnosing HGUC in TPS for urine cytology 22,43 . Although urine cytology is highly accurate for detecting HGUC, its sensitivity remains relatively low, even with TPS 44,45 . Thus, the presence of a predictive marker for HGUC, in addition to urine cytology, might be helpful in daily practice.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological significance of TUBB3 in upper tract urothelial carcinoma and possible application in urine cytology

Kobayashi,

Hayashi,

Sentani

et al. 2023

Pathology International

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AbstractβIII‐Tubulin, encoded by the TUBB3 gene, is a microtubule protein. We previously reported that TUBB3 is overexpressed in renal cell carcinoma. We investigated the clinicopathological significance of TUBB3 in upper tract urothelial carcinoma (UTUC) by immunohistochemistry. In normal tissue, TUBB3 expression was weak or absent. In contrast, TUBB3 overexpression was observed in urothelial carcinoma (UC) tissues in 51 (49%) of 103 UTUC cases. TUBB3 overexpression was associated with nodular/flat morphology, high‐grade disease, high T stage, and a poor prognosis. Similar results were obtained in The Cancer Genome Atlas bladder cancer cohort. TUBB3 expression was also associated with high Ki‐67 labeling index, CD44v9, HER2, EGFR, and p53 expression in UTUC. Among representative cancer‐related molecules, TUBB3 was an independent predictor of progression‐free survival and high‐grade UC. Finally, using urine cytology samples, we analyzed TUBB3 expression by immunocytochemistry. TUBB3 expression was more frequently found in UC cells than in nonneoplastic cells. The diagnostic accuracy of urine cytology was improved when combined with TUBB3 immunostaining. The findings suggest the importance of TUBB3 in tumor progression and its potential application as a biomarker for high‐grade disease and the prognosis of UC. Moreover, combination with TUBB3 immunostaining might improve the diagnostic accuracy of urine cytology.

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The Paris System for reporting urinary cytology improves the negative predictive value of high-grade urothelial carcinoma

Cited by 16 publications

References 18 publications

Are we on track for diagnosing high‐grade urothelial carcinoma with a minimum quantity of five malignant cells in lower tract specimens? Critical analysis of The Paris System Quantitation Criteria

Are we on track for diagnosing high‐grade urothelial carcinoma with a minimum quantity of five malignant cells in lower tract specimens? Critical analysis of The Paris System Quantitation Criteria

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

Clinicopathological significance of TUBB3 in upper tract urothelial carcinoma and possible application in urine cytology

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