NET G3 vs NEC: p53 and Rb1 Immunolabeling in High-grade Gastrointestinal Neuroendocrine Neoplasms - Is It Enough for the Differential Diagnosis?
High-grade gastrointestinal neuroendocrine neoplasms (GI-NENs) are divided into well-differentiated G3 neuroendocrine tumors (NETs G3) and neuroendocrine carcinomas (NECs), having identical cut-offs of proliferation, but different biomolecular origins. This translates in distinct treatment choices....
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| Veröffentlicht in: | Journal of gastrointestinal and liver diseases : JGLD 2023-06, Vol.32 (2), p.162-169 |
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| creator | Dinu, Alexandra Aschie, Mariana Cozaru, Georgeta Camelia Mitroi, Anca Florentina Grasa, Catalin Nicolae Iordache, Ionut Eduard Deacu, Mariana Orasanu, Cristian Ionut Nicolau, Antonela-Anca Baltatescu, Gabriela Izabela |
| description | High-grade gastrointestinal neuroendocrine neoplasms (GI-NENs) are divided into well-differentiated G3 neuroendocrine tumors (NETs G3) and neuroendocrine carcinomas (NECs), having identical cut-offs of proliferation, but different biomolecular origins. This translates in distinct treatment choices. Our aim was to establish if p53/Rb1 immunohistochemical status in GI-NENs with Ki67 index >20% can predict the histopathological diagnosis.
p53/Rb1 immunolabelling was performed on 42 cases of high-grade GI-NENs, diagnosed as NET G3, NEC and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) with NEC component. Immunolabeled slides were digitally scanned, with automatic quantification of p53 and Rb1, blind to the diagnosis.
The p53 positive percentage was stratified; two cut-offs were selected, naming the intervals as N (null, 20%). The Rb1 expression loss in >90% of neoplastic cells was considered mutational. NETs G3 mainly showed the T status (14/16, 87.5%), followed by N (1/16, 6.25%) and C (1/16, 6.25%); NECs and NEC components in MiNENs predominantly expressed the C status (19/26, 73.08%), followed by N (5/26, 19.23%) and T (2/26, 7.69%) (p |
| doi_str_mv | 10.15403/jgld-4654 |
| format | Article |
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p53/Rb1 immunolabelling was performed on 42 cases of high-grade GI-NENs, diagnosed as NET G3, NEC and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) with NEC component. Immunolabeled slides were digitally scanned, with automatic quantification of p53 and Rb1, blind to the diagnosis.
The p53 positive percentage was stratified; two cut-offs were selected, naming the intervals as N (null, <1%), T (tumor, 1%-20%) and C (carcinoma, >20%). The Rb1 expression loss in >90% of neoplastic cells was considered mutational. NETs G3 mainly showed the T status (14/16, 87.5%), followed by N (1/16, 6.25%) and C (1/16, 6.25%); NECs and NEC components in MiNENs predominantly expressed the C status (19/26, 73.08%), followed by N (5/26, 19.23%) and T (2/26, 7.69%) (p<0.001, χ 2 =27.017). NET G3s showed positive expression for Rb1; 73.08% of NECs expressed negative Rb1 (p<0.001, χ 2 =21.351). NECs and NEC components in MiNENs showed Rb1 mutational status in 13 C cases (13/19, 68.42%), 4 N cases (4/5, 80%) and in both the T cases (p=0.002, χ 2 =11.187).
Our results highlight the correlations between the p53/Rb1 immunostainings and the histopathological diagnosis of high-grade GI-NENs. NECs and NEC components in MiNENs showed a p53 mutational status (0% or 21-100%) and predominantly negative Rb1 expression. NETs G3 showed a p53 wild-type status (1-20%) and retained Rb1 expression. These findings suggest that the differential diagnosis of high-grade GI-NENs may benefit from p53/Rb1 immunohistochemical tests in everyday practice.</description><identifier>ISSN: 1841-8724</identifier><identifier>EISSN: 1842-1121</identifier><identifier>DOI: 10.15403/jgld-4654</identifier><identifier>PMID: 37345605</identifier><language>eng</language><publisher>Romania</publisher><subject>Carcinoma, Neuroendocrine - diagnosis ; Carcinoma, Neuroendocrine - genetics ; Carcinoma, Neuroendocrine - pathology ; Diagnosis, Differential ; Gastrointestinal Neoplasms - diagnosis ; Gastrointestinal Neoplasms - genetics ; Humans ; Neuroendocrine Tumors - diagnosis ; Neuroendocrine Tumors - genetics ; Neuroendocrine Tumors - metabolism ; Pancreatic Neoplasms - pathology ; Tumor Suppressor Protein p53 - genetics</subject><ispartof>Journal of gastrointestinal and liver diseases : JGLD, 2023-06, Vol.32 (2), p.162-169</ispartof><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c287t-e1810b75fb2c0322354f682b3fb80e2d0a028da384875ab2846caefd79777e123</citedby><orcidid>0000-0003-0202-5933 ; 0000-0001-8039-3200 ; 0000-0001-7857-0562 ; 0000-0002-8998-2332 ; 0000-0002-0569-4289 ; 0000-0002-4255-586X ; 0000-0002-9251-3297 ; 0000-0002-3391-8200 ; 0000-0003-1910-9797</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37345605$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dinu, Alexandra</creatorcontrib><creatorcontrib>Aschie, Mariana</creatorcontrib><creatorcontrib>Cozaru, Georgeta Camelia</creatorcontrib><creatorcontrib>Mitroi, Anca Florentina</creatorcontrib><creatorcontrib>Grasa, Catalin Nicolae</creatorcontrib><creatorcontrib>Iordache, Ionut Eduard</creatorcontrib><creatorcontrib>Deacu, Mariana</creatorcontrib><creatorcontrib>Orasanu, Cristian Ionut</creatorcontrib><creatorcontrib>Nicolau, Antonela-Anca</creatorcontrib><creatorcontrib>Baltatescu, Gabriela Izabela</creatorcontrib><title>NET G3 vs NEC: p53 and Rb1 Immunolabeling in High-grade Gastrointestinal Neuroendocrine Neoplasms - Is It Enough for the Differential Diagnosis?</title><title>Journal of gastrointestinal and liver diseases : JGLD</title><addtitle>J Gastrointestin Liver Dis</addtitle><description>High-grade gastrointestinal neuroendocrine neoplasms (GI-NENs) are divided into well-differentiated G3 neuroendocrine tumors (NETs G3) and neuroendocrine carcinomas (NECs), having identical cut-offs of proliferation, but different biomolecular origins. This translates in distinct treatment choices. Our aim was to establish if p53/Rb1 immunohistochemical status in GI-NENs with Ki67 index >20% can predict the histopathological diagnosis.
p53/Rb1 immunolabelling was performed on 42 cases of high-grade GI-NENs, diagnosed as NET G3, NEC and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) with NEC component. Immunolabeled slides were digitally scanned, with automatic quantification of p53 and Rb1, blind to the diagnosis.
The p53 positive percentage was stratified; two cut-offs were selected, naming the intervals as N (null, <1%), T (tumor, 1%-20%) and C (carcinoma, >20%). The Rb1 expression loss in >90% of neoplastic cells was considered mutational. NETs G3 mainly showed the T status (14/16, 87.5%), followed by N (1/16, 6.25%) and C (1/16, 6.25%); NECs and NEC components in MiNENs predominantly expressed the C status (19/26, 73.08%), followed by N (5/26, 19.23%) and T (2/26, 7.69%) (p<0.001, χ 2 =27.017). NET G3s showed positive expression for Rb1; 73.08% of NECs expressed negative Rb1 (p<0.001, χ 2 =21.351). NECs and NEC components in MiNENs showed Rb1 mutational status in 13 C cases (13/19, 68.42%), 4 N cases (4/5, 80%) and in both the T cases (p=0.002, χ 2 =11.187).
Our results highlight the correlations between the p53/Rb1 immunostainings and the histopathological diagnosis of high-grade GI-NENs. NECs and NEC components in MiNENs showed a p53 mutational status (0% or 21-100%) and predominantly negative Rb1 expression. NETs G3 showed a p53 wild-type status (1-20%) and retained Rb1 expression. These findings suggest that the differential diagnosis of high-grade GI-NENs may benefit from p53/Rb1 immunohistochemical tests in everyday practice.</description><subject>Carcinoma, Neuroendocrine - diagnosis</subject><subject>Carcinoma, Neuroendocrine - genetics</subject><subject>Carcinoma, Neuroendocrine - pathology</subject><subject>Diagnosis, Differential</subject><subject>Gastrointestinal Neoplasms - diagnosis</subject><subject>Gastrointestinal Neoplasms - genetics</subject><subject>Humans</subject><subject>Neuroendocrine Tumors - diagnosis</subject><subject>Neuroendocrine Tumors - genetics</subject><subject>Neuroendocrine Tumors - metabolism</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><issn>1841-8724</issn><issn>1842-1121</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kM1KAzEUhYMotlY3PoDctTCav5lENyJtbQulgtT1kJlJpikzSUlmBN_CR7atP6t7LnznLD6Ergm-IynH7H5bN1XCs5SfoCGRnCaEUHJ6zCSRgvIBuohxi3GWYSHO0YAJxtMMp0P0tZquYcbgI8JqOn6EXcpAuQreCgKLtu2db1ShG-tqsA7mtt4kdVCVhpmKXfDWdTp21qkGVroPXrvKl8E6vX_9rlGxjZDAIsKig6nzfb0B4wN0Gw0Ta4wO2nV2X55YVTsfbXy6RGdGNVFf_d4Ren-ZrsfzZPk6W4yfl0lJpegSTSTBhUhNQUvMKGUpN5mkBTOFxJpWWGEqK8UklyJVBZU8K5U2lXgQQmhC2Qjd_uyWwccYtMl3wbYqfOYE50et-UFrftC6h29-4F1ftLr6R_88sm_BSXLG</recordid><startdate>20230622</startdate><enddate>20230622</enddate><creator>Dinu, Alexandra</creator><creator>Aschie, Mariana</creator><creator>Cozaru, Georgeta Camelia</creator><creator>Mitroi, Anca Florentina</creator><creator>Grasa, Catalin Nicolae</creator><creator>Iordache, Ionut Eduard</creator><creator>Deacu, Mariana</creator><creator>Orasanu, Cristian Ionut</creator><creator>Nicolau, Antonela-Anca</creator><creator>Baltatescu, Gabriela Izabela</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0003-0202-5933</orcidid><orcidid>https://orcid.org/0000-0001-8039-3200</orcidid><orcidid>https://orcid.org/0000-0001-7857-0562</orcidid><orcidid>https://orcid.org/0000-0002-8998-2332</orcidid><orcidid>https://orcid.org/0000-0002-0569-4289</orcidid><orcidid>https://orcid.org/0000-0002-4255-586X</orcidid><orcidid>https://orcid.org/0000-0002-9251-3297</orcidid><orcidid>https://orcid.org/0000-0002-3391-8200</orcidid><orcidid>https://orcid.org/0000-0003-1910-9797</orcidid></search><sort><creationdate>20230622</creationdate><title>NET G3 vs NEC: p53 and Rb1 Immunolabeling in High-grade Gastrointestinal Neuroendocrine Neoplasms - Is It Enough for the Differential Diagnosis?</title><author>Dinu, Alexandra ; Aschie, Mariana ; Cozaru, Georgeta Camelia ; Mitroi, Anca Florentina ; Grasa, Catalin Nicolae ; Iordache, Ionut Eduard ; Deacu, Mariana ; Orasanu, Cristian Ionut ; Nicolau, Antonela-Anca ; Baltatescu, Gabriela Izabela</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c287t-e1810b75fb2c0322354f682b3fb80e2d0a028da384875ab2846caefd79777e123</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Carcinoma, Neuroendocrine - diagnosis</topic><topic>Carcinoma, Neuroendocrine - genetics</topic><topic>Carcinoma, Neuroendocrine - pathology</topic><topic>Diagnosis, Differential</topic><topic>Gastrointestinal Neoplasms - diagnosis</topic><topic>Gastrointestinal Neoplasms - genetics</topic><topic>Humans</topic><topic>Neuroendocrine Tumors - diagnosis</topic><topic>Neuroendocrine Tumors - genetics</topic><topic>Neuroendocrine Tumors - metabolism</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><toplevel>online_resources</toplevel><creatorcontrib>Dinu, Alexandra</creatorcontrib><creatorcontrib>Aschie, Mariana</creatorcontrib><creatorcontrib>Cozaru, Georgeta Camelia</creatorcontrib><creatorcontrib>Mitroi, Anca Florentina</creatorcontrib><creatorcontrib>Grasa, Catalin Nicolae</creatorcontrib><creatorcontrib>Iordache, Ionut Eduard</creatorcontrib><creatorcontrib>Deacu, Mariana</creatorcontrib><creatorcontrib>Orasanu, Cristian Ionut</creatorcontrib><creatorcontrib>Nicolau, Antonela-Anca</creatorcontrib><creatorcontrib>Baltatescu, Gabriela Izabela</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of gastrointestinal and liver diseases : JGLD</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dinu, Alexandra</au><au>Aschie, Mariana</au><au>Cozaru, Georgeta Camelia</au><au>Mitroi, Anca Florentina</au><au>Grasa, Catalin Nicolae</au><au>Iordache, Ionut Eduard</au><au>Deacu, Mariana</au><au>Orasanu, Cristian Ionut</au><au>Nicolau, Antonela-Anca</au><au>Baltatescu, Gabriela Izabela</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>NET G3 vs NEC: p53 and Rb1 Immunolabeling in High-grade Gastrointestinal Neuroendocrine Neoplasms - Is It Enough for the Differential Diagnosis?</atitle><jtitle>Journal of gastrointestinal and liver diseases : JGLD</jtitle><addtitle>J Gastrointestin Liver Dis</addtitle><date>2023-06-22</date><risdate>2023</risdate><volume>32</volume><issue>2</issue><spage>162</spage><epage>169</epage><pages>162-169</pages><issn>1841-8724</issn><eissn>1842-1121</eissn><abstract>High-grade gastrointestinal neuroendocrine neoplasms (GI-NENs) are divided into well-differentiated G3 neuroendocrine tumors (NETs G3) and neuroendocrine carcinomas (NECs), having identical cut-offs of proliferation, but different biomolecular origins. This translates in distinct treatment choices. Our aim was to establish if p53/Rb1 immunohistochemical status in GI-NENs with Ki67 index >20% can predict the histopathological diagnosis.
p53/Rb1 immunolabelling was performed on 42 cases of high-grade GI-NENs, diagnosed as NET G3, NEC and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) with NEC component. Immunolabeled slides were digitally scanned, with automatic quantification of p53 and Rb1, blind to the diagnosis.
The p53 positive percentage was stratified; two cut-offs were selected, naming the intervals as N (null, <1%), T (tumor, 1%-20%) and C (carcinoma, >20%). The Rb1 expression loss in >90% of neoplastic cells was considered mutational. NETs G3 mainly showed the T status (14/16, 87.5%), followed by N (1/16, 6.25%) and C (1/16, 6.25%); NECs and NEC components in MiNENs predominantly expressed the C status (19/26, 73.08%), followed by N (5/26, 19.23%) and T (2/26, 7.69%) (p<0.001, χ 2 =27.017). NET G3s showed positive expression for Rb1; 73.08% of NECs expressed negative Rb1 (p<0.001, χ 2 =21.351). NECs and NEC components in MiNENs showed Rb1 mutational status in 13 C cases (13/19, 68.42%), 4 N cases (4/5, 80%) and in both the T cases (p=0.002, χ 2 =11.187).
Our results highlight the correlations between the p53/Rb1 immunostainings and the histopathological diagnosis of high-grade GI-NENs. NECs and NEC components in MiNENs showed a p53 mutational status (0% or 21-100%) and predominantly negative Rb1 expression. NETs G3 showed a p53 wild-type status (1-20%) and retained Rb1 expression. These findings suggest that the differential diagnosis of high-grade GI-NENs may benefit from p53/Rb1 immunohistochemical tests in everyday practice.</abstract><cop>Romania</cop><pmid>37345605</pmid><doi>10.15403/jgld-4654</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-0202-5933</orcidid><orcidid>https://orcid.org/0000-0001-8039-3200</orcidid><orcidid>https://orcid.org/0000-0001-7857-0562</orcidid><orcidid>https://orcid.org/0000-0002-8998-2332</orcidid><orcidid>https://orcid.org/0000-0002-0569-4289</orcidid><orcidid>https://orcid.org/0000-0002-4255-586X</orcidid><orcidid>https://orcid.org/0000-0002-9251-3297</orcidid><orcidid>https://orcid.org/0000-0002-3391-8200</orcidid><orcidid>https://orcid.org/0000-0003-1910-9797</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Carcinoma, Neuroendocrine - diagnosis Carcinoma, Neuroendocrine - genetics Carcinoma, Neuroendocrine - pathology Diagnosis, Differential Gastrointestinal Neoplasms - diagnosis Gastrointestinal Neoplasms - genetics Humans Neuroendocrine Tumors - diagnosis Neuroendocrine Tumors - genetics Neuroendocrine Tumors - metabolism Pancreatic Neoplasms - pathology Tumor Suppressor Protein p53 - genetics |
| title | NET G3 vs NEC: p53 and Rb1 Immunolabeling in High-grade Gastrointestinal Neuroendocrine Neoplasms - Is It Enough for the Differential Diagnosis? |
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