Analysis of Molecular Pretreated Tumor Profiles as Predictive Biomarkers of Therapeutic Response and Survival Outcomes after Neoadjuvant Therapy for Rectal Cancer in Moroccan Population
Pathologic features depending on tumor response to preoperative chemoradiotherapy are important to determine the outcomes in patients with rectal cancer. Evaluating the potential predictive roles of biomarker expression and their prognostic impact is a promising challenge. We reported here the immun...
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| Veröffentlicht in: | Disease markers 2020, Vol.2020, p.8459303-11 |
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| creator | El Otmani, Ihsane El Agy, Fatima El Baradai, Sanae Bouguenouch, Laila Lahmidani, Nada El Abkari, Mohammed Benajah, Dafr Allah Toughrai, Imane El Bouhaddouti, Hicham Mouaqit, Ouadii Ibn Majdoub Hassani, Karim Mazaz, Khalid Benjelloun, El Bachir Ousadden, Abdelmalek El Rhazi, Karima Bouhafa, Touria Benbrahim, Zineb Ouldim, Karim Ibrahimi, Sidi Adil Ait Taleb, Khalid Chbani, Laila |
| description | Pathologic features depending on tumor response to preoperative chemoradiotherapy are important to determine the outcomes in patients with rectal cancer. Evaluating the potential predictive roles of biomarker expression and their prognostic impact is a promising challenge. We reported here the immunohistochemical staining of a panel marker of mismatch repair protein (MMR), Ki67, HER-2, and p53. Additionally, identification of somatic mutations of KRAS, NRAS, and BRAF genes were performed by direct sequencing and pyrosequencing in pretreated biopsy tissues from 57 patients diagnosed for rectal cancer. Clinical features and pathological criteria for postneoadjuvant treatment surgical resection specimen’s data were collected. Immunohistochemical expression and mutational status were correlated with therapeutic response, overall survival, and disease progression. The mean age of patients was 56 years. Seven (12.3%) out of 57 patients had a complete therapeutic response. Our analysis showed that when using complete therapeutic response (Dworak 4) and incomplete therapeutic response (Dworak 3, 2, and 1) as grouping factor, high p53 expression at the pretreatment biopsy was significantly associated to an incomplete response (p=0.002). For 20 and 2 out of 57, KRAS and NRAS mutations were detected, respectively. The majority of these mutations affected codon 12. KRAS mutations detected at codon 146 (A146T, A146V) was associated with the appearance of recurrence and distant metastasis (p=0.019). A high expression of HER-2 corresponding to score 3+ was observed in 3 pretreatment biopsy specimens. This class was significantly associated with a short relapse-free survival (p=0.002). Furthermore, the high expression of Ki67 was moderately correlated with an older age (p=0.016, r=0.319). In addition, this shows that high p53 expression in the pretreatment biopsy was associated with an incomplete response in surgical resection specimens after neoadjuvant treatment, and a HER-2 score 3+ can be a predictive factor of distant metastasis and local recurrence. Larger, prospective, and more studies are needed. |
| doi_str_mv | 10.1155/2020/8459303 |
| format | Article |
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Evaluating the potential predictive roles of biomarker expression and their prognostic impact is a promising challenge. We reported here the immunohistochemical staining of a panel marker of mismatch repair protein (MMR), Ki67, HER-2, and p53. Additionally, identification of somatic mutations of KRAS, NRAS, and BRAF genes were performed by direct sequencing and pyrosequencing in pretreated biopsy tissues from 57 patients diagnosed for rectal cancer. Clinical features and pathological criteria for postneoadjuvant treatment surgical resection specimen’s data were collected. Immunohistochemical expression and mutational status were correlated with therapeutic response, overall survival, and disease progression. The mean age of patients was 56 years. Seven (12.3%) out of 57 patients had a complete therapeutic response. Our analysis showed that when using complete therapeutic response (Dworak 4) and incomplete therapeutic response (Dworak 3, 2, and 1) as grouping factor, high p53 expression at the pretreatment biopsy was significantly associated to an incomplete response (p=0.002). For 20 and 2 out of 57, KRAS and NRAS mutations were detected, respectively. The majority of these mutations affected codon 12. KRAS mutations detected at codon 146 (A146T, A146V) was associated with the appearance of recurrence and distant metastasis (p=0.019). A high expression of HER-2 corresponding to score 3+ was observed in 3 pretreatment biopsy specimens. This class was significantly associated with a short relapse-free survival (p=0.002). Furthermore, the high expression of Ki67 was moderately correlated with an older age (p=0.016, r=0.319). In addition, this shows that high p53 expression in the pretreatment biopsy was associated with an incomplete response in surgical resection specimens after neoadjuvant treatment, and a HER-2 score 3+ can be a predictive factor of distant metastasis and local recurrence. Larger, prospective, and more studies are needed.</description><identifier>ISSN: 0278-0240</identifier><identifier>ISSN: 1875-8630</identifier><identifier>EISSN: 1875-8630</identifier><identifier>DOI: 10.1155/2020/8459303</identifier><identifier>PMID: 31998419</identifier><language>eng</language><publisher>United States: Hindawi</publisher><subject>Adjuvant treatment ; Adult ; Aged ; Analysis ; Biomarkers ; Biopsy ; Cancer ; Cancer patients ; Cancer therapies ; Carcinoma - genetics ; Carcinoma - metabolism ; Carcinoma - pathology ; Carcinoma - therapy ; Chemoradiotherapy ; Cloning ; Codon ; Colorectal cancer ; Deoxyribonucleic acid ; DNA ; ErbB-2 protein ; Female ; Gene sequencing ; GTP Phosphohydrolases - genetics ; GTP Phosphohydrolases - metabolism ; Hassan II, King of Morocco ; HER protein ; Humans ; Immunoglobulins ; Immunohistochemistry ; K-Ras protein ; Ki-67 Antigen - genetics ; Ki-67 Antigen - metabolism ; Male ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Metastases ; Middle Aged ; Mismatch repair ; Mutation ; Neoadjuvant Therapy ; p53 Protein ; Patient outcomes ; Patients ; Proteins ; Proto-Oncogene Proteins B-raf - genetics ; Proto-Oncogene Proteins B-raf - metabolism ; Proto-Oncogene Proteins p21(ras) - genetics ; Proto-Oncogene Proteins p21(ras) - metabolism ; Radiation therapy ; Receptor, ErbB-2 - genetics ; Receptor, ErbB-2 - metabolism ; Rectal Neoplasms - genetics ; Rectal Neoplasms - metabolism ; Rectal Neoplasms - pathology ; Rectal Neoplasms - therapy ; Rectum ; Statistical analysis ; Survival ; Treatment Outcome ; Tumor proteins ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Protein p53 - metabolism ; Tumors</subject><ispartof>Disease markers, 2020, Vol.2020, p.8459303-11</ispartof><rights>Copyright © 2020 Ihsane El Otmani et al.</rights><rights>COPYRIGHT 2020 John Wiley & Sons, Inc.</rights><rights>Copyright © 2020 Ihsane El Otmani et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. http://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2020 Ihsane El Otmani et al. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c476t-1de107d8629a171417c79777c60ff1a35ea709c7ccc12d1af6bd67bbb4fd86903</citedby><cites>FETCH-LOGICAL-c476t-1de107d8629a171417c79777c60ff1a35ea709c7ccc12d1af6bd67bbb4fd86903</cites><orcidid>0000-0002-2031-3640 ; 0000-0001-8473-9432 ; 0000-0002-4467-4555</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977322/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977322/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,4014,27914,27915,27916,53782,53784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31998419$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Bamonti, Fabrizia</contributor><contributor>Fabrizia Bamonti</contributor><creatorcontrib>El Otmani, Ihsane</creatorcontrib><creatorcontrib>El Agy, Fatima</creatorcontrib><creatorcontrib>El Baradai, Sanae</creatorcontrib><creatorcontrib>Bouguenouch, Laila</creatorcontrib><creatorcontrib>Lahmidani, Nada</creatorcontrib><creatorcontrib>El Abkari, Mohammed</creatorcontrib><creatorcontrib>Benajah, Dafr Allah</creatorcontrib><creatorcontrib>Toughrai, Imane</creatorcontrib><creatorcontrib>El Bouhaddouti, Hicham</creatorcontrib><creatorcontrib>Mouaqit, Ouadii</creatorcontrib><creatorcontrib>Ibn Majdoub Hassani, Karim</creatorcontrib><creatorcontrib>Mazaz, Khalid</creatorcontrib><creatorcontrib>Benjelloun, El Bachir</creatorcontrib><creatorcontrib>Ousadden, Abdelmalek</creatorcontrib><creatorcontrib>El Rhazi, Karima</creatorcontrib><creatorcontrib>Bouhafa, Touria</creatorcontrib><creatorcontrib>Benbrahim, Zineb</creatorcontrib><creatorcontrib>Ouldim, Karim</creatorcontrib><creatorcontrib>Ibrahimi, Sidi Adil</creatorcontrib><creatorcontrib>Ait Taleb, Khalid</creatorcontrib><creatorcontrib>Chbani, Laila</creatorcontrib><title>Analysis of Molecular Pretreated Tumor Profiles as Predictive Biomarkers of Therapeutic Response and Survival Outcomes after Neoadjuvant Therapy for Rectal Cancer in Moroccan Population</title><title>Disease markers</title><addtitle>Dis Markers</addtitle><description>Pathologic features depending on tumor response to preoperative chemoradiotherapy are important to determine the outcomes in patients with rectal cancer. Evaluating the potential predictive roles of biomarker expression and their prognostic impact is a promising challenge. We reported here the immunohistochemical staining of a panel marker of mismatch repair protein (MMR), Ki67, HER-2, and p53. Additionally, identification of somatic mutations of KRAS, NRAS, and BRAF genes were performed by direct sequencing and pyrosequencing in pretreated biopsy tissues from 57 patients diagnosed for rectal cancer. Clinical features and pathological criteria for postneoadjuvant treatment surgical resection specimen’s data were collected. Immunohistochemical expression and mutational status were correlated with therapeutic response, overall survival, and disease progression. The mean age of patients was 56 years. Seven (12.3%) out of 57 patients had a complete therapeutic response. Our analysis showed that when using complete therapeutic response (Dworak 4) and incomplete therapeutic response (Dworak 3, 2, and 1) as grouping factor, high p53 expression at the pretreatment biopsy was significantly associated to an incomplete response (p=0.002). For 20 and 2 out of 57, KRAS and NRAS mutations were detected, respectively. The majority of these mutations affected codon 12. KRAS mutations detected at codon 146 (A146T, A146V) was associated with the appearance of recurrence and distant metastasis (p=0.019). A high expression of HER-2 corresponding to score 3+ was observed in 3 pretreatment biopsy specimens. This class was significantly associated with a short relapse-free survival (p=0.002). Furthermore, the high expression of Ki67 was moderately correlated with an older age (p=0.016, r=0.319). In addition, this shows that high p53 expression in the pretreatment biopsy was associated with an incomplete response in surgical resection specimens after neoadjuvant treatment, and a HER-2 score 3+ can be a predictive factor of distant metastasis and local recurrence. Larger, prospective, and more studies are needed.</description><subject>Adjuvant treatment</subject><subject>Adult</subject><subject>Aged</subject><subject>Analysis</subject><subject>Biomarkers</subject><subject>Biopsy</subject><subject>Cancer</subject><subject>Cancer patients</subject><subject>Cancer therapies</subject><subject>Carcinoma - genetics</subject><subject>Carcinoma - metabolism</subject><subject>Carcinoma - pathology</subject><subject>Carcinoma - therapy</subject><subject>Chemoradiotherapy</subject><subject>Cloning</subject><subject>Codon</subject><subject>Colorectal cancer</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>ErbB-2 protein</subject><subject>Female</subject><subject>Gene sequencing</subject><subject>GTP Phosphohydrolases - genetics</subject><subject>GTP Phosphohydrolases - metabolism</subject><subject>Hassan II, King of Morocco</subject><subject>HER protein</subject><subject>Humans</subject><subject>Immunoglobulins</subject><subject>Immunohistochemistry</subject><subject>K-Ras protein</subject><subject>Ki-67 Antigen - genetics</subject><subject>Ki-67 Antigen - metabolism</subject><subject>Male</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Metastases</subject><subject>Middle Aged</subject><subject>Mismatch repair</subject><subject>Mutation</subject><subject>Neoadjuvant Therapy</subject><subject>p53 Protein</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins B-raf - genetics</subject><subject>Proto-Oncogene Proteins B-raf - metabolism</subject><subject>Proto-Oncogene Proteins p21(ras) - genetics</subject><subject>Proto-Oncogene Proteins p21(ras) - metabolism</subject><subject>Radiation therapy</subject><subject>Receptor, ErbB-2 - genetics</subject><subject>Receptor, ErbB-2 - metabolism</subject><subject>Rectal Neoplasms - genetics</subject><subject>Rectal Neoplasms - metabolism</subject><subject>Rectal Neoplasms - pathology</subject><subject>Rectal Neoplasms - therapy</subject><subject>Rectum</subject><subject>Statistical analysis</subject><subject>Survival</subject><subject>Treatment Outcome</subject><subject>Tumor proteins</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Tumors</subject><issn>0278-0240</issn><issn>1875-8630</issn><issn>1875-8630</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>EIF</sourceid><recordid>eNp9kk1vEzEQhlcIREvhxhlZ4oIEobb3w-sLUoj4kgqtSjhbE--4cdjYwfYG5afx7_AmoXwcOFnyPPPOO5q3KB4z-pKxuj7nlNPztqplScs7xSlrRT1pm5LeLU4pF-2E8oqeFA9iXFHKuKzk_eKkZFK2FZOnxY-pg34XbSTekI--Rz30EMhVwBQQEnZkPqz9-OGN7TESiGOxszrZLZLX1q8hfMWw758vMcAGh2Q1uca48S4iAdeRz0PY2i305HJI2q9HGZMwkE_ooVsNW3Dp2LwjJk-7Rp0yPQOnM2Vddha81uDIld9kg8l697C4Z6CP-Oj4nhVf3r6Zz95PLi7ffZhNLya6Ek2asA4ZFV3bcAlMsIoJLaQQQjfUGAZljSCo1EJrzXjHwDSLrhGLxaIyuUnS8qx4ddDdDIs1dhpdCtCrTbB5853yYNXfFWeX6sZvVZPHlJxngWdHgeC_DRiTWtuose_BoR-i4mXVtlSwtsro03_QlR9CvtCeYlVZc0F_UzfQo7LO-DxXj6Jq2jDJM7f3_eJA6eBjDGhuLTOqxuSoMTnqmJyMP_lzzVv4V1Qy8PwALK3r4Lv9v9xPs-TOtA</recordid><startdate>2020</startdate><enddate>2020</enddate><creator>El Otmani, Ihsane</creator><creator>El Agy, Fatima</creator><creator>El Baradai, Sanae</creator><creator>Bouguenouch, Laila</creator><creator>Lahmidani, Nada</creator><creator>El Abkari, Mohammed</creator><creator>Benajah, Dafr Allah</creator><creator>Toughrai, Imane</creator><creator>El Bouhaddouti, Hicham</creator><creator>Mouaqit, Ouadii</creator><creator>Ibn Majdoub Hassani, Karim</creator><creator>Mazaz, Khalid</creator><creator>Benjelloun, El Bachir</creator><creator>Ousadden, Abdelmalek</creator><creator>El Rhazi, Karima</creator><creator>Bouhafa, Touria</creator><creator>Benbrahim, Zineb</creator><creator>Ouldim, Karim</creator><creator>Ibrahimi, Sidi Adil</creator><creator>Ait Taleb, Khalid</creator><creator>Chbani, Laila</creator><general>Hindawi</general><general>John Wiley & Sons, Inc</general><general>Hindawi Limited</general><scope>RHU</scope><scope>RHW</scope><scope>RHX</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>7QL</scope><scope>7QO</scope><scope>7TK</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2031-3640</orcidid><orcidid>https://orcid.org/0000-0001-8473-9432</orcidid><orcidid>https://orcid.org/0000-0002-4467-4555</orcidid></search><sort><creationdate>2020</creationdate><title>Analysis of Molecular Pretreated Tumor Profiles as Predictive Biomarkers of Therapeutic Response and Survival Outcomes after Neoadjuvant Therapy for Rectal Cancer in Moroccan Population</title><author>El Otmani, Ihsane ; El Agy, Fatima ; El Baradai, Sanae ; Bouguenouch, Laila ; Lahmidani, Nada ; El Abkari, Mohammed ; Benajah, Dafr Allah ; Toughrai, Imane ; El Bouhaddouti, Hicham ; Mouaqit, Ouadii ; Ibn Majdoub Hassani, Karim ; Mazaz, Khalid ; Benjelloun, El Bachir ; Ousadden, Abdelmalek ; El Rhazi, Karima ; Bouhafa, Touria ; Benbrahim, Zineb ; Ouldim, Karim ; Ibrahimi, Sidi Adil ; Ait Taleb, Khalid ; Chbani, Laila</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c476t-1de107d8629a171417c79777c60ff1a35ea709c7ccc12d1af6bd67bbb4fd86903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adjuvant treatment</topic><topic>Adult</topic><topic>Aged</topic><topic>Analysis</topic><topic>Biomarkers</topic><topic>Biopsy</topic><topic>Cancer</topic><topic>Cancer patients</topic><topic>Cancer therapies</topic><topic>Carcinoma - genetics</topic><topic>Carcinoma - metabolism</topic><topic>Carcinoma - pathology</topic><topic>Carcinoma - therapy</topic><topic>Chemoradiotherapy</topic><topic>Cloning</topic><topic>Codon</topic><topic>Colorectal cancer</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>ErbB-2 protein</topic><topic>Female</topic><topic>Gene sequencing</topic><topic>GTP Phosphohydrolases - genetics</topic><topic>GTP Phosphohydrolases - metabolism</topic><topic>Hassan II, King of Morocco</topic><topic>HER protein</topic><topic>Humans</topic><topic>Immunoglobulins</topic><topic>Immunohistochemistry</topic><topic>K-Ras protein</topic><topic>Ki-67 Antigen - genetics</topic><topic>Ki-67 Antigen - metabolism</topic><topic>Male</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Metastases</topic><topic>Middle Aged</topic><topic>Mismatch repair</topic><topic>Mutation</topic><topic>Neoadjuvant Therapy</topic><topic>p53 Protein</topic><topic>Patient outcomes</topic><topic>Patients</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins B-raf - genetics</topic><topic>Proto-Oncogene Proteins B-raf - metabolism</topic><topic>Proto-Oncogene Proteins p21(ras) - genetics</topic><topic>Proto-Oncogene Proteins p21(ras) - metabolism</topic><topic>Radiation therapy</topic><topic>Receptor, ErbB-2 - genetics</topic><topic>Receptor, ErbB-2 - metabolism</topic><topic>Rectal Neoplasms - genetics</topic><topic>Rectal Neoplasms - metabolism</topic><topic>Rectal Neoplasms - pathology</topic><topic>Rectal Neoplasms - therapy</topic><topic>Rectum</topic><topic>Statistical analysis</topic><topic>Survival</topic><topic>Treatment Outcome</topic><topic>Tumor proteins</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>El Otmani, Ihsane</creatorcontrib><creatorcontrib>El Agy, Fatima</creatorcontrib><creatorcontrib>El Baradai, Sanae</creatorcontrib><creatorcontrib>Bouguenouch, Laila</creatorcontrib><creatorcontrib>Lahmidani, Nada</creatorcontrib><creatorcontrib>El Abkari, Mohammed</creatorcontrib><creatorcontrib>Benajah, Dafr Allah</creatorcontrib><creatorcontrib>Toughrai, Imane</creatorcontrib><creatorcontrib>El Bouhaddouti, Hicham</creatorcontrib><creatorcontrib>Mouaqit, Ouadii</creatorcontrib><creatorcontrib>Ibn Majdoub Hassani, Karim</creatorcontrib><creatorcontrib>Mazaz, Khalid</creatorcontrib><creatorcontrib>Benjelloun, El Bachir</creatorcontrib><creatorcontrib>Ousadden, Abdelmalek</creatorcontrib><creatorcontrib>El Rhazi, Karima</creatorcontrib><creatorcontrib>Bouhafa, Touria</creatorcontrib><creatorcontrib>Benbrahim, Zineb</creatorcontrib><creatorcontrib>Ouldim, Karim</creatorcontrib><creatorcontrib>Ibrahimi, Sidi Adil</creatorcontrib><creatorcontrib>Ait Taleb, Khalid</creatorcontrib><creatorcontrib>Chbani, Laila</creatorcontrib><collection>Hindawi Publishing Complete</collection><collection>Hindawi Publishing Subscription Journals</collection><collection>Hindawi Publishing Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Disease markers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>El Otmani, Ihsane</au><au>El Agy, Fatima</au><au>El Baradai, Sanae</au><au>Bouguenouch, Laila</au><au>Lahmidani, Nada</au><au>El Abkari, Mohammed</au><au>Benajah, Dafr Allah</au><au>Toughrai, Imane</au><au>El Bouhaddouti, Hicham</au><au>Mouaqit, Ouadii</au><au>Ibn Majdoub Hassani, Karim</au><au>Mazaz, Khalid</au><au>Benjelloun, El Bachir</au><au>Ousadden, Abdelmalek</au><au>El Rhazi, Karima</au><au>Bouhafa, Touria</au><au>Benbrahim, Zineb</au><au>Ouldim, Karim</au><au>Ibrahimi, Sidi Adil</au><au>Ait Taleb, Khalid</au><au>Chbani, Laila</au><au>Bamonti, Fabrizia</au><au>Fabrizia Bamonti</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Analysis of Molecular Pretreated Tumor Profiles as Predictive Biomarkers of Therapeutic Response and Survival Outcomes after Neoadjuvant Therapy for Rectal Cancer in Moroccan Population</atitle><jtitle>Disease markers</jtitle><addtitle>Dis Markers</addtitle><date>2020</date><risdate>2020</risdate><volume>2020</volume><spage>8459303</spage><epage>11</epage><pages>8459303-11</pages><issn>0278-0240</issn><issn>1875-8630</issn><eissn>1875-8630</eissn><abstract>Pathologic features depending on tumor response to preoperative chemoradiotherapy are important to determine the outcomes in patients with rectal cancer. Evaluating the potential predictive roles of biomarker expression and their prognostic impact is a promising challenge. We reported here the immunohistochemical staining of a panel marker of mismatch repair protein (MMR), Ki67, HER-2, and p53. Additionally, identification of somatic mutations of KRAS, NRAS, and BRAF genes were performed by direct sequencing and pyrosequencing in pretreated biopsy tissues from 57 patients diagnosed for rectal cancer. Clinical features and pathological criteria for postneoadjuvant treatment surgical resection specimen’s data were collected. Immunohistochemical expression and mutational status were correlated with therapeutic response, overall survival, and disease progression. The mean age of patients was 56 years. Seven (12.3%) out of 57 patients had a complete therapeutic response. Our analysis showed that when using complete therapeutic response (Dworak 4) and incomplete therapeutic response (Dworak 3, 2, and 1) as grouping factor, high p53 expression at the pretreatment biopsy was significantly associated to an incomplete response (p=0.002). For 20 and 2 out of 57, KRAS and NRAS mutations were detected, respectively. The majority of these mutations affected codon 12. KRAS mutations detected at codon 146 (A146T, A146V) was associated with the appearance of recurrence and distant metastasis (p=0.019). A high expression of HER-2 corresponding to score 3+ was observed in 3 pretreatment biopsy specimens. This class was significantly associated with a short relapse-free survival (p=0.002). Furthermore, the high expression of Ki67 was moderately correlated with an older age (p=0.016, r=0.319). In addition, this shows that high p53 expression in the pretreatment biopsy was associated with an incomplete response in surgical resection specimens after neoadjuvant treatment, and a HER-2 score 3+ can be a predictive factor of distant metastasis and local recurrence. Larger, prospective, and more studies are needed.</abstract><cop>United States</cop><pub>Hindawi</pub><pmid>31998419</pmid><doi>10.1155/2020/8459303</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-2031-3640</orcidid><orcidid>https://orcid.org/0000-0001-8473-9432</orcidid><orcidid>https://orcid.org/0000-0002-4467-4555</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0278-0240 |
| ispartof | Disease markers, 2020, Vol.2020, p.8459303-11 |
| issn | 0278-0240 1875-8630 1875-8630 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6977322 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Wiley-Blackwell Open Access Titles; PubMed Central; Alma/SFX Local Collection |
| subjects | Adjuvant treatment Adult Aged Analysis Biomarkers Biopsy Cancer Cancer patients Cancer therapies Carcinoma - genetics Carcinoma - metabolism Carcinoma - pathology Carcinoma - therapy Chemoradiotherapy Cloning Codon Colorectal cancer Deoxyribonucleic acid DNA ErbB-2 protein Female Gene sequencing GTP Phosphohydrolases - genetics GTP Phosphohydrolases - metabolism Hassan II, King of Morocco HER protein Humans Immunoglobulins Immunohistochemistry K-Ras protein Ki-67 Antigen - genetics Ki-67 Antigen - metabolism Male Membrane Proteins - genetics Membrane Proteins - metabolism Metastases Middle Aged Mismatch repair Mutation Neoadjuvant Therapy p53 Protein Patient outcomes Patients Proteins Proto-Oncogene Proteins B-raf - genetics Proto-Oncogene Proteins B-raf - metabolism Proto-Oncogene Proteins p21(ras) - genetics Proto-Oncogene Proteins p21(ras) - metabolism Radiation therapy Receptor, ErbB-2 - genetics Receptor, ErbB-2 - metabolism Rectal Neoplasms - genetics Rectal Neoplasms - metabolism Rectal Neoplasms - pathology Rectal Neoplasms - therapy Rectum Statistical analysis Survival Treatment Outcome Tumor proteins Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism Tumors |
| title | Analysis of Molecular Pretreated Tumor Profiles as Predictive Biomarkers of Therapeutic Response and Survival Outcomes after Neoadjuvant Therapy for Rectal Cancer in Moroccan Population |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-15T03%3A51%3A56IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Analysis%20of%20Molecular%20Pretreated%20Tumor%20Profiles%20as%20Predictive%20Biomarkers%20of%20Therapeutic%20Response%20and%20Survival%20Outcomes%20after%20Neoadjuvant%20Therapy%20for%20Rectal%20Cancer%20in%20Moroccan%20Population&rft.jtitle=Disease%20markers&rft.au=El%20Otmani,%20Ihsane&rft.date=2020&rft.volume=2020&rft.spage=8459303&rft.epage=11&rft.pages=8459303-11&rft.issn=0278-0240&rft.eissn=1875-8630&rft_id=info:doi/10.1155/2020/8459303&rft_dat=%3Cgale_pubme%3EA619214390%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2341435270&rft_id=info:pmid/31998419&rft_galeid=A619214390&rfr_iscdi=true |