Clinicopathological significance of claspin overexpression and its efficacy as a novel biomarker for the diagnosis of urothelial carcinoma
We previously reported that claspin is a key regulator in the progression of gastric cancer and renal cell carcinoma. However, the clinicopathological significance of claspin in urothelial carcinoma (UC) has not been investigated. We analyzed the expression and distribution of claspin in UC cases by...
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| Veröffentlicht in: | Virchows Archiv : an international journal of pathology 2022-03, Vol.480 (3), p.621-633 |
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| creator | Kobayashi, Go Hayashi, Tetsutaro Sentani, Kazuhiro Babasaki, Takashi Sekino, Yohei Inoue, Shogo Uraoka, Naohiro Hanamoto, Masanori Nose, Hiroyuki Teishima, Jun Oue, Naohide Matsubara, Akio Sasaki, Naomi Yasui, Wataru |
| description | We previously reported that claspin is a key regulator in the progression of gastric cancer and renal cell carcinoma. However, the clinicopathological significance of claspin in urothelial carcinoma (UC) has not been investigated. We analyzed the expression and distribution of claspin in UC cases by immunohistochemistry. In the non-neoplastic urothelium, the expression of claspin was either weak or absent, whereas UC tissues showed nuclear staining. The expression of claspin was detected in 58 (42%) of a total of 138 upper tract UC cases treated by radical nephroureterectomy without neoadjuvant chemotherapy. Claspin-positive UC cases were associated with nodular/flat morphology, variant histology, high tumor grade, high pathological T grade, and lymphatic and venous invasion. The expression of claspin was significantly associated with decreased progression-free survival and cancer-specific survival. In addition, claspin was co-expressed with Ki-67, PD-L1, HER2, EGFR, and p53 in consecutive tumor sections of UC. An immunohistochemical analysis of claspin in biopsy specimens revealed that strong to moderate claspin staining was more frequently observed in carcinoma in situ in comparison to dysplasia or the benign urothelium. Furthermore, immunocytochemistry for claspin on urine cytology slides demonstrated that the proportion of claspin-positive cells was significantly greater in high-grade UC than in benign cases. These results suggest that claspin may be a novel prognostic marker and a possible therapeutic target molecule for UC. Moreover, claspin could be a useful diagnostic biomarker of urothelial neoplasia. |
| doi_str_mv | 10.1007/s00428-021-03239-7 |
| format | Article |
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However, the clinicopathological significance of claspin in urothelial carcinoma (UC) has not been investigated. We analyzed the expression and distribution of claspin in UC cases by immunohistochemistry. In the non-neoplastic urothelium, the expression of claspin was either weak or absent, whereas UC tissues showed nuclear staining. The expression of claspin was detected in 58 (42%) of a total of 138 upper tract UC cases treated by radical nephroureterectomy without neoadjuvant chemotherapy. Claspin-positive UC cases were associated with nodular/flat morphology, variant histology, high tumor grade, high pathological T grade, and lymphatic and venous invasion. The expression of claspin was significantly associated with decreased progression-free survival and cancer-specific survival. In addition, claspin was co-expressed with Ki-67, PD-L1, HER2, EGFR, and p53 in consecutive tumor sections of UC. An immunohistochemical analysis of claspin in biopsy specimens revealed that strong to moderate claspin staining was more frequently observed in carcinoma in situ in comparison to dysplasia or the benign urothelium. Furthermore, immunocytochemistry for claspin on urine cytology slides demonstrated that the proportion of claspin-positive cells was significantly greater in high-grade UC than in benign cases. These results suggest that claspin may be a novel prognostic marker and a possible therapeutic target molecule for UC. Moreover, claspin could be a useful diagnostic biomarker of urothelial neoplasia.</description><identifier>ISSN: 0945-6317</identifier><identifier>EISSN: 1432-2307</identifier><identifier>DOI: 10.1007/s00428-021-03239-7</identifier><identifier>PMID: 34842980</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Biomarkers ; Biomarkers - analysis ; Biomarkers, Tumor - analysis ; Biopsy ; Bladder cancer ; Cancer ; Carcinoma, Transitional Cell - pathology ; Chemotherapy ; Cytology ; Dysplasia ; ErbB-2 protein ; Gastric cancer ; Histology ; Humans ; Immunocytochemistry ; Immunohistochemistry ; Kidney cancer ; Kidney Neoplasms - pathology ; Medical diagnosis ; Medicine ; Medicine & Public Health ; Original Article ; Pathology ; PD-L1 protein ; Renal cell carcinoma ; Staining ; Survival ; Therapeutic targets ; Tumors ; Urinary Bladder Neoplasms - pathology ; Urothelial carcinoma ; Urothelium ; Urothelium - pathology</subject><ispartof>Virchows Archiv : an international journal of pathology, 2022-03, Vol.480 (3), p.621-633</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021</rights><rights>2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c441t-78057806088c9a6a7bb42e2724f7790b7e7a9ee00f97314487251baec657a1663</citedby><cites>FETCH-LOGICAL-c441t-78057806088c9a6a7bb42e2724f7790b7e7a9ee00f97314487251baec657a1663</cites><orcidid>0000-0002-8987-5414</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00428-021-03239-7$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00428-021-03239-7$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34842980$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kobayashi, Go</creatorcontrib><creatorcontrib>Hayashi, Tetsutaro</creatorcontrib><creatorcontrib>Sentani, Kazuhiro</creatorcontrib><creatorcontrib>Babasaki, Takashi</creatorcontrib><creatorcontrib>Sekino, Yohei</creatorcontrib><creatorcontrib>Inoue, Shogo</creatorcontrib><creatorcontrib>Uraoka, Naohiro</creatorcontrib><creatorcontrib>Hanamoto, Masanori</creatorcontrib><creatorcontrib>Nose, Hiroyuki</creatorcontrib><creatorcontrib>Teishima, Jun</creatorcontrib><creatorcontrib>Oue, Naohide</creatorcontrib><creatorcontrib>Matsubara, Akio</creatorcontrib><creatorcontrib>Sasaki, Naomi</creatorcontrib><creatorcontrib>Yasui, Wataru</creatorcontrib><title>Clinicopathological significance of claspin overexpression and its efficacy as a novel biomarker for the diagnosis of urothelial carcinoma</title><title>Virchows Archiv : an international journal of pathology</title><addtitle>Virchows Arch</addtitle><addtitle>Virchows Arch</addtitle><description>We previously reported that claspin is a key regulator in the progression of gastric cancer and renal cell carcinoma. However, the clinicopathological significance of claspin in urothelial carcinoma (UC) has not been investigated. We analyzed the expression and distribution of claspin in UC cases by immunohistochemistry. In the non-neoplastic urothelium, the expression of claspin was either weak or absent, whereas UC tissues showed nuclear staining. The expression of claspin was detected in 58 (42%) of a total of 138 upper tract UC cases treated by radical nephroureterectomy without neoadjuvant chemotherapy. Claspin-positive UC cases were associated with nodular/flat morphology, variant histology, high tumor grade, high pathological T grade, and lymphatic and venous invasion. The expression of claspin was significantly associated with decreased progression-free survival and cancer-specific survival. In addition, claspin was co-expressed with Ki-67, PD-L1, HER2, EGFR, and p53 in consecutive tumor sections of UC. An immunohistochemical analysis of claspin in biopsy specimens revealed that strong to moderate claspin staining was more frequently observed in carcinoma in situ in comparison to dysplasia or the benign urothelium. Furthermore, immunocytochemistry for claspin on urine cytology slides demonstrated that the proportion of claspin-positive cells was significantly greater in high-grade UC than in benign cases. These results suggest that claspin may be a novel prognostic marker and a possible therapeutic target molecule for UC. Moreover, claspin could be a useful diagnostic biomarker of urothelial neoplasia.</description><subject>Biomarkers</subject><subject>Biomarkers - analysis</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Biopsy</subject><subject>Bladder cancer</subject><subject>Cancer</subject><subject>Carcinoma, Transitional Cell - pathology</subject><subject>Chemotherapy</subject><subject>Cytology</subject><subject>Dysplasia</subject><subject>ErbB-2 protein</subject><subject>Gastric cancer</subject><subject>Histology</subject><subject>Humans</subject><subject>Immunocytochemistry</subject><subject>Immunohistochemistry</subject><subject>Kidney cancer</subject><subject>Kidney Neoplasms - pathology</subject><subject>Medical diagnosis</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Original Article</subject><subject>Pathology</subject><subject>PD-L1 protein</subject><subject>Renal cell carcinoma</subject><subject>Staining</subject><subject>Survival</subject><subject>Therapeutic targets</subject><subject>Tumors</subject><subject>Urinary Bladder Neoplasms - 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However, the clinicopathological significance of claspin in urothelial carcinoma (UC) has not been investigated. We analyzed the expression and distribution of claspin in UC cases by immunohistochemistry. In the non-neoplastic urothelium, the expression of claspin was either weak or absent, whereas UC tissues showed nuclear staining. The expression of claspin was detected in 58 (42%) of a total of 138 upper tract UC cases treated by radical nephroureterectomy without neoadjuvant chemotherapy. Claspin-positive UC cases were associated with nodular/flat morphology, variant histology, high tumor grade, high pathological T grade, and lymphatic and venous invasion. The expression of claspin was significantly associated with decreased progression-free survival and cancer-specific survival. In addition, claspin was co-expressed with Ki-67, PD-L1, HER2, EGFR, and p53 in consecutive tumor sections of UC. An immunohistochemical analysis of claspin in biopsy specimens revealed that strong to moderate claspin staining was more frequently observed in carcinoma in situ in comparison to dysplasia or the benign urothelium. Furthermore, immunocytochemistry for claspin on urine cytology slides demonstrated that the proportion of claspin-positive cells was significantly greater in high-grade UC than in benign cases. These results suggest that claspin may be a novel prognostic marker and a possible therapeutic target molecule for UC. Moreover, claspin could be a useful diagnostic biomarker of urothelial neoplasia.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>34842980</pmid><doi>10.1007/s00428-021-03239-7</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-8987-5414</orcidid></addata></record> |
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| subjects | Biomarkers Biomarkers - analysis Biomarkers, Tumor - analysis Biopsy Bladder cancer Cancer Carcinoma, Transitional Cell - pathology Chemotherapy Cytology Dysplasia ErbB-2 protein Gastric cancer Histology Humans Immunocytochemistry Immunohistochemistry Kidney cancer Kidney Neoplasms - pathology Medical diagnosis Medicine Medicine & Public Health Original Article Pathology PD-L1 protein Renal cell carcinoma Staining Survival Therapeutic targets Tumors Urinary Bladder Neoplasms - pathology Urothelial carcinoma Urothelium Urothelium - pathology |
| title | Clinicopathological significance of claspin overexpression and its efficacy as a novel biomarker for the diagnosis of urothelial carcinoma |
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