Validation of the prognostic value of histopathological grading or c-kit mutation in canine cutaneous mast cell tumours: A retrospective cohort study
The objective of this retrospective cohort study was to validate the prognostic value of histological grading of canine cutaneous mast cell tumours (MCTs) according to the Patnaik (grades I–III) and Kiupel (low, high) grading systems, and to confirm the prognostic significance of internal tandem dup...
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Veröffentlicht in: | The veterinary journal (1997) 2013-06, Vol.196 (3), p.492-498 |
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creator | Takeuchi, Yoshinori Fujino, Yasuhito Watanabe, Manabu Takahashi, Masashi Nakagawa, Takayuki Takeuchi, Ayano Bonkobara, Makoto Kobayashi, Tetsuya Ohno, Koichi Uchida, Kazuyuki Asano, Kazushi Nishimura, Ryohei Nakayama, Hiroyuki Sugano, Sumio Ohashi, Yasuo Tsujimoto, Hajime |
description | The objective of this retrospective cohort study was to validate the prognostic value of histological grading of canine cutaneous mast cell tumours (MCTs) according to the Patnaik (grades I–III) and Kiupel (low, high) grading systems, and to confirm the prognostic significance of internal tandem duplications (ITDs) within exon 11 of the c-kit gene (ITD-Exon11). The baseline characteristics and outcome data from 47 dogs diagnosed with cutaneous MCTs were collected and reviewed. Tumours were graded according to both grading systems and the nucleotide sequence of c-kit was evaluated. Results were analyzed to evaluate predictive factors for overall survival (OS) and progression-free survival (PFS).
Log-rank tests indicated that dogs with Patnaik grade III MCTs had significantly reduced OS and PFS compared to those with either grade I or II tumours. However, no significant difference in OS or PFS was observed between grade I and II tumours. The dogs with Kiupel high-grade MCTs had significantly shorter OS and PFS than dogs with low-grade MCTs. The presence of ITD-Exon11 was significantly associated with shorter PFS. The result of Cox regression analysis showed that the Kiupel grading system for OS and PFS, and lymph node metastasis for OS, independently predicted prognosis. Kappa statistics confirmed a significantly higher inter-observer consistency for the Kiupel compared to the Patnaik grading system. These findings demonstrate that the Kiupel grading system is a useful prognostic tool for canine cutaneous MCTs in predicting OS and PFS, while the occurrence of ITD-Exon11 appeared to be a useful predictor for PFS. |
doi_str_mv | 10.1016/j.tvjl.2012.11.018 |
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Log-rank tests indicated that dogs with Patnaik grade III MCTs had significantly reduced OS and PFS compared to those with either grade I or II tumours. However, no significant difference in OS or PFS was observed between grade I and II tumours. The dogs with Kiupel high-grade MCTs had significantly shorter OS and PFS than dogs with low-grade MCTs. The presence of ITD-Exon11 was significantly associated with shorter PFS. The result of Cox regression analysis showed that the Kiupel grading system for OS and PFS, and lymph node metastasis for OS, independently predicted prognosis. Kappa statistics confirmed a significantly higher inter-observer consistency for the Kiupel compared to the Patnaik grading system. These findings demonstrate that the Kiupel grading system is a useful prognostic tool for canine cutaneous MCTs in predicting OS and PFS, while the occurrence of ITD-Exon11 appeared to be a useful predictor for PFS.</description><identifier>ISSN: 1090-0233</identifier><identifier>EISSN: 1532-2971</identifier><identifier>DOI: 10.1016/j.tvjl.2012.11.018</identifier><identifier>PMID: 23384436</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Cohort Studies ; Dog ; Dog Diseases - metabolism ; Dogs ; exons ; Female ; genes ; histopathology ; Indexing in process ; lymph nodes ; Male ; Mast cell tumour ; Mastocytoma - genetics ; Mastocytoma - metabolism ; Mastocytoma - veterinary ; metastasis ; mutation ; neoplasms ; Oncology ; prediction ; Predictive Value of Tests ; prognosis ; Prognostic factor ; Proto-Oncogene Proteins c-kit - genetics ; Proto-Oncogene Proteins c-kit - metabolism ; regression analysis ; Reproducibility of Results ; Retrospective Studies ; Skin Neoplasms - genetics ; Skin Neoplasms - metabolism ; Skin Neoplasms - veterinary ; Survival analysis</subject><ispartof>The veterinary journal (1997), 2013-06, Vol.196 (3), p.492-498</ispartof><rights>2012</rights><rights>Copyright © 2012. Published by Elsevier Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c413t-bcdbe1e5c7f4cb3922692e41b21cf32cdfe6cb735319d2c6831e960e9c021053</citedby><cites>FETCH-LOGICAL-c413t-bcdbe1e5c7f4cb3922692e41b21cf32cdfe6cb735319d2c6831e960e9c021053</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.tvjl.2012.11.018$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,778,782,3539,27907,27908,45978</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23384436$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Takeuchi, Yoshinori</creatorcontrib><creatorcontrib>Fujino, Yasuhito</creatorcontrib><creatorcontrib>Watanabe, Manabu</creatorcontrib><creatorcontrib>Takahashi, Masashi</creatorcontrib><creatorcontrib>Nakagawa, Takayuki</creatorcontrib><creatorcontrib>Takeuchi, Ayano</creatorcontrib><creatorcontrib>Bonkobara, Makoto</creatorcontrib><creatorcontrib>Kobayashi, Tetsuya</creatorcontrib><creatorcontrib>Ohno, Koichi</creatorcontrib><creatorcontrib>Uchida, Kazuyuki</creatorcontrib><creatorcontrib>Asano, Kazushi</creatorcontrib><creatorcontrib>Nishimura, Ryohei</creatorcontrib><creatorcontrib>Nakayama, Hiroyuki</creatorcontrib><creatorcontrib>Sugano, Sumio</creatorcontrib><creatorcontrib>Ohashi, Yasuo</creatorcontrib><creatorcontrib>Tsujimoto, Hajime</creatorcontrib><title>Validation of the prognostic value of histopathological grading or c-kit mutation in canine cutaneous mast cell tumours: A retrospective cohort study</title><title>The veterinary journal (1997)</title><addtitle>Vet J</addtitle><description>The objective of this retrospective cohort study was to validate the prognostic value of histological grading of canine cutaneous mast cell tumours (MCTs) according to the Patnaik (grades I–III) and Kiupel (low, high) grading systems, and to confirm the prognostic significance of internal tandem duplications (ITDs) within exon 11 of the c-kit gene (ITD-Exon11). The baseline characteristics and outcome data from 47 dogs diagnosed with cutaneous MCTs were collected and reviewed. Tumours were graded according to both grading systems and the nucleotide sequence of c-kit was evaluated. Results were analyzed to evaluate predictive factors for overall survival (OS) and progression-free survival (PFS).
Log-rank tests indicated that dogs with Patnaik grade III MCTs had significantly reduced OS and PFS compared to those with either grade I or II tumours. However, no significant difference in OS or PFS was observed between grade I and II tumours. The dogs with Kiupel high-grade MCTs had significantly shorter OS and PFS than dogs with low-grade MCTs. The presence of ITD-Exon11 was significantly associated with shorter PFS. The result of Cox regression analysis showed that the Kiupel grading system for OS and PFS, and lymph node metastasis for OS, independently predicted prognosis. Kappa statistics confirmed a significantly higher inter-observer consistency for the Kiupel compared to the Patnaik grading system. These findings demonstrate that the Kiupel grading system is a useful prognostic tool for canine cutaneous MCTs in predicting OS and PFS, while the occurrence of ITD-Exon11 appeared to be a useful predictor for PFS.</description><subject>Animals</subject><subject>Cohort Studies</subject><subject>Dog</subject><subject>Dog Diseases - metabolism</subject><subject>Dogs</subject><subject>exons</subject><subject>Female</subject><subject>genes</subject><subject>histopathology</subject><subject>Indexing in process</subject><subject>lymph nodes</subject><subject>Male</subject><subject>Mast cell tumour</subject><subject>Mastocytoma - genetics</subject><subject>Mastocytoma - metabolism</subject><subject>Mastocytoma - veterinary</subject><subject>metastasis</subject><subject>mutation</subject><subject>neoplasms</subject><subject>Oncology</subject><subject>prediction</subject><subject>Predictive Value of Tests</subject><subject>prognosis</subject><subject>Prognostic factor</subject><subject>Proto-Oncogene Proteins c-kit - genetics</subject><subject>Proto-Oncogene Proteins c-kit - metabolism</subject><subject>regression analysis</subject><subject>Reproducibility of Results</subject><subject>Retrospective Studies</subject><subject>Skin Neoplasms - genetics</subject><subject>Skin Neoplasms - metabolism</subject><subject>Skin Neoplasms - veterinary</subject><subject>Survival analysis</subject><issn>1090-0233</issn><issn>1532-2971</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1u1TAQhSMEoj_wAizAy24SPHZ-rhGbqqKAVIkFha3lTCa5viTxxXau1AfhfXGUwhKxsMYafXN0Zk6WvQJeAIf67aGIp8NYCA6iACg47J5k51BJkQvVwNP054rnXEh5ll2EcOCcq7IUz7Oz1NqVpazPs1_fzWg7E62bmetZ3BM7ejfMLkSL7GTGhdb-3obojibu3egGi2ZkgzednQfmPMP8h41sWuImY2eGZrYzMUytmdwS2GRCZEjjyOIyucWHd-yaeYrehSNhtKcEu73zkYW4dA8vsme9GQO9fKyX2f3th_ubT_ndl4-fb67vcixBxrzFriWgCpu-xFYqIWolqIRWAPZSYNdTjW0jKwmqE1jvJJCqOSnkAnglL7OrTTat_HOhEPVkw-pyc62hVKKugP8PKpsUQ80rnlCxoZi2C556ffR2Mv5BA9drcPqg1-D0GpwG0Cm4NPT6UX9pJ-r-jvxJKgFvNqA3TpvB26C_fU0KFU9PNLVKxPuNoHSxkyWvA1qakTrr04115-y_HPwGJxG2Fw</recordid><startdate>20130601</startdate><enddate>20130601</enddate><creator>Takeuchi, Yoshinori</creator><creator>Fujino, Yasuhito</creator><creator>Watanabe, Manabu</creator><creator>Takahashi, Masashi</creator><creator>Nakagawa, Takayuki</creator><creator>Takeuchi, Ayano</creator><creator>Bonkobara, Makoto</creator><creator>Kobayashi, Tetsuya</creator><creator>Ohno, Koichi</creator><creator>Uchida, Kazuyuki</creator><creator>Asano, Kazushi</creator><creator>Nishimura, Ryohei</creator><creator>Nakayama, Hiroyuki</creator><creator>Sugano, Sumio</creator><creator>Ohashi, Yasuo</creator><creator>Tsujimoto, Hajime</creator><general>Elsevier Ltd</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>F1W</scope><scope>H95</scope><scope>H98</scope><scope>L.G</scope></search><sort><creationdate>20130601</creationdate><title>Validation of the prognostic value of histopathological grading or c-kit mutation in canine cutaneous mast cell tumours: A retrospective cohort study</title><author>Takeuchi, Yoshinori ; Fujino, Yasuhito ; Watanabe, Manabu ; Takahashi, Masashi ; Nakagawa, Takayuki ; Takeuchi, Ayano ; Bonkobara, Makoto ; Kobayashi, Tetsuya ; Ohno, Koichi ; Uchida, Kazuyuki ; Asano, Kazushi ; Nishimura, Ryohei ; Nakayama, Hiroyuki ; Sugano, Sumio ; Ohashi, Yasuo ; Tsujimoto, Hajime</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c413t-bcdbe1e5c7f4cb3922692e41b21cf32cdfe6cb735319d2c6831e960e9c021053</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Cohort Studies</topic><topic>Dog</topic><topic>Dog Diseases - metabolism</topic><topic>Dogs</topic><topic>exons</topic><topic>Female</topic><topic>genes</topic><topic>histopathology</topic><topic>Indexing in process</topic><topic>lymph nodes</topic><topic>Male</topic><topic>Mast cell tumour</topic><topic>Mastocytoma - genetics</topic><topic>Mastocytoma - metabolism</topic><topic>Mastocytoma - veterinary</topic><topic>metastasis</topic><topic>mutation</topic><topic>neoplasms</topic><topic>Oncology</topic><topic>prediction</topic><topic>Predictive Value of Tests</topic><topic>prognosis</topic><topic>Prognostic factor</topic><topic>Proto-Oncogene Proteins c-kit - genetics</topic><topic>Proto-Oncogene Proteins c-kit - metabolism</topic><topic>regression analysis</topic><topic>Reproducibility of Results</topic><topic>Retrospective Studies</topic><topic>Skin Neoplasms - genetics</topic><topic>Skin Neoplasms - metabolism</topic><topic>Skin Neoplasms - veterinary</topic><topic>Survival analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Takeuchi, Yoshinori</creatorcontrib><creatorcontrib>Fujino, Yasuhito</creatorcontrib><creatorcontrib>Watanabe, Manabu</creatorcontrib><creatorcontrib>Takahashi, Masashi</creatorcontrib><creatorcontrib>Nakagawa, Takayuki</creatorcontrib><creatorcontrib>Takeuchi, Ayano</creatorcontrib><creatorcontrib>Bonkobara, Makoto</creatorcontrib><creatorcontrib>Kobayashi, Tetsuya</creatorcontrib><creatorcontrib>Ohno, Koichi</creatorcontrib><creatorcontrib>Uchida, Kazuyuki</creatorcontrib><creatorcontrib>Asano, Kazushi</creatorcontrib><creatorcontrib>Nishimura, Ryohei</creatorcontrib><creatorcontrib>Nakayama, Hiroyuki</creatorcontrib><creatorcontrib>Sugano, Sumio</creatorcontrib><creatorcontrib>Ohashi, Yasuo</creatorcontrib><creatorcontrib>Tsujimoto, Hajime</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Aquaculture Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><jtitle>The veterinary journal (1997)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Takeuchi, Yoshinori</au><au>Fujino, Yasuhito</au><au>Watanabe, Manabu</au><au>Takahashi, Masashi</au><au>Nakagawa, Takayuki</au><au>Takeuchi, Ayano</au><au>Bonkobara, Makoto</au><au>Kobayashi, Tetsuya</au><au>Ohno, Koichi</au><au>Uchida, Kazuyuki</au><au>Asano, Kazushi</au><au>Nishimura, Ryohei</au><au>Nakayama, Hiroyuki</au><au>Sugano, Sumio</au><au>Ohashi, Yasuo</au><au>Tsujimoto, Hajime</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Validation of the prognostic value of histopathological grading or c-kit mutation in canine cutaneous mast cell tumours: A retrospective cohort study</atitle><jtitle>The veterinary journal (1997)</jtitle><addtitle>Vet J</addtitle><date>2013-06-01</date><risdate>2013</risdate><volume>196</volume><issue>3</issue><spage>492</spage><epage>498</epage><pages>492-498</pages><issn>1090-0233</issn><eissn>1532-2971</eissn><abstract>The objective of this retrospective cohort study was to validate the prognostic value of histological grading of canine cutaneous mast cell tumours (MCTs) according to the Patnaik (grades I–III) and Kiupel (low, high) grading systems, and to confirm the prognostic significance of internal tandem duplications (ITDs) within exon 11 of the c-kit gene (ITD-Exon11). The baseline characteristics and outcome data from 47 dogs diagnosed with cutaneous MCTs were collected and reviewed. Tumours were graded according to both grading systems and the nucleotide sequence of c-kit was evaluated. Results were analyzed to evaluate predictive factors for overall survival (OS) and progression-free survival (PFS).
Log-rank tests indicated that dogs with Patnaik grade III MCTs had significantly reduced OS and PFS compared to those with either grade I or II tumours. However, no significant difference in OS or PFS was observed between grade I and II tumours. The dogs with Kiupel high-grade MCTs had significantly shorter OS and PFS than dogs with low-grade MCTs. The presence of ITD-Exon11 was significantly associated with shorter PFS. The result of Cox regression analysis showed that the Kiupel grading system for OS and PFS, and lymph node metastasis for OS, independently predicted prognosis. Kappa statistics confirmed a significantly higher inter-observer consistency for the Kiupel compared to the Patnaik grading system. These findings demonstrate that the Kiupel grading system is a useful prognostic tool for canine cutaneous MCTs in predicting OS and PFS, while the occurrence of ITD-Exon11 appeared to be a useful predictor for PFS.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>23384436</pmid><doi>10.1016/j.tvjl.2012.11.018</doi><tpages>7</tpages></addata></record> |
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subjects | Animals Cohort Studies Dog Dog Diseases - metabolism Dogs exons Female genes histopathology Indexing in process lymph nodes Male Mast cell tumour Mastocytoma - genetics Mastocytoma - metabolism Mastocytoma - veterinary metastasis mutation neoplasms Oncology prediction Predictive Value of Tests prognosis Prognostic factor Proto-Oncogene Proteins c-kit - genetics Proto-Oncogene Proteins c-kit - metabolism regression analysis Reproducibility of Results Retrospective Studies Skin Neoplasms - genetics Skin Neoplasms - metabolism Skin Neoplasms - veterinary Survival analysis |
title | Validation of the prognostic value of histopathological grading or c-kit mutation in canine cutaneous mast cell tumours: A retrospective cohort study |
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