Prognostic and Clinicopathological Correlations of Cell Cycle Marker Expressions before and after the Primary Systemic Therapy of Breast Cancer
We aimed to analyze the expression of cell-cycle regulation markers – minichromosome maintenance protein 2 (MCM2), Ki-67, Cyclin-A and phosphohistone-H3 (PHH3) − in pre-treatment core-biopsy samples of breast carcinomas in correlation with known predictive and prognostic factors. Totally 52 core bio...
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| creator | Tőkés, Tímea Tőkés, Anna-Mária Szentmártoni, Gyöngyvér Kiszner, Gergő Mühl, Dorottya Molnár, Béla Ákos Kulka, Janina Krenács, Tibor Dank, Magdolna |
| description | We aimed to analyze the expression of cell-cycle regulation markers – minichromosome maintenance protein 2 (MCM2), Ki-67, Cyclin-A and phosphohistone-H3 (PHH3) − in pre-treatment core-biopsy samples of breast carcinomas in correlation with known predictive and prognostic factors. Totally 52 core biopsy samples obtained prior to neoadjuvant therapy were analyzed. Immunohistochemistry was performed to analyze the expression of MCM2, Ki-67, Cyclin A and PHH3, which were correlated with the following clinicopathological parameters: clinical TNM, tumor grade, biological subtype, the presence of tumor infiltrating lymphocytes (TIL), pathological tumor response rate to the neoadjuvant therapy and patient survival. All investigated markers showed higher expression in high grade and in triple negative tumors (
p
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| doi_str_mv | 10.1007/s12253-019-00726-w |
| format | Article |
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p
< 0.01 and
p
< 0.05, respectively). Hormone receptor negative tumors showed significantly higher expression of Ki-67 (p < 0.01), MCM2 (p < 0.01) and Cyclin A (p < 0.01) than hormone receptor positive ones. Tumors with increased TIL showed significantly higher Ki-67 expression (
p
= 0.04). Pattern analysis suggested that novel cell-cycle marker-based subgrouping reveals predictive and prognostic potential. Tumors with high MCM2, Cyclin A or PHH3 expression showed significantly higher rate of pathological complete remission. Tumors with early relapse (progression-free survival ≤2 years) and shortened overall survival also show a higher rate of proliferation. Our cell cycle marker (Ki-67, MCM2, Cyclin A, PHH3) based testing could identify tumors with worse prognosis, but with a favorable response to primary systemic therapy. The pattern of cell-cycle activity could also be useful for predicting early relapse, but our findings need to be further substantiated in larger patient cohorts.</description><identifier>ISSN: 1219-4956</identifier><identifier>EISSN: 1532-2807</identifier><identifier>DOI: 10.1007/s12253-019-00726-w</identifier><identifier>PMID: 31446607</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Adult ; Aged ; Antineoplastic Agents - therapeutic use ; Biomarkers, Tumor - analysis ; Biomedical and Life Sciences ; Biomedicine ; Biopsy ; Breast cancer ; Breast carcinoma ; Breast Neoplasms - drug therapy ; Breast Neoplasms - pathology ; Cancer Research ; Cell cycle ; Cell Cycle - drug effects ; Cell Cycle Proteins - analysis ; Cell Cycle Proteins - drug effects ; Cell Cycle Proteins - metabolism ; Cyclin A ; Female ; Humans ; Immunohistochemistry ; Immunology ; Life Sciences & Biomedicine ; Lymphocytes ; Lymphocytes, Tumor-Infiltrating - drug effects ; Lymphocytes, Tumor-Infiltrating - pathology ; Medical prognosis ; Middle Aged ; Oncology ; Original ; Original Article ; Pathology ; Patients ; Prognosis ; Remission ; Science & Technology ; Survival ; Tumors</subject><ispartof>Pathology oncology research, 2020-07, Vol.26 (3), p.1499-1510</ispartof><rights>The Author(s) 2019</rights><rights>Pathology & Oncology Research is a copyright of Springer, (2019). All Rights Reserved. © 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2019. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>8</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000540615800017</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c502t-7fccebe7a1978a6e38f6289867d53d283c6a51d441c1f9775d250afaed26811a3</citedby><cites>FETCH-LOGICAL-c502t-7fccebe7a1978a6e38f6289867d53d283c6a51d441c1f9775d250afaed26811a3</cites><orcidid>0000-0002-5456-1706</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/s12253-019-00726-w$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12253-019-00726-w$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,315,781,785,886,27929,27930,28253,41493,42562,51324</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31446607$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tőkés, Tímea</creatorcontrib><creatorcontrib>Tőkés, Anna-Mária</creatorcontrib><creatorcontrib>Szentmártoni, Gyöngyvér</creatorcontrib><creatorcontrib>Kiszner, Gergő</creatorcontrib><creatorcontrib>Mühl, Dorottya</creatorcontrib><creatorcontrib>Molnár, Béla Ákos</creatorcontrib><creatorcontrib>Kulka, Janina</creatorcontrib><creatorcontrib>Krenács, Tibor</creatorcontrib><creatorcontrib>Dank, Magdolna</creatorcontrib><title>Prognostic and Clinicopathological Correlations of Cell Cycle Marker Expressions before and after the Primary Systemic Therapy of Breast Cancer</title><title>Pathology oncology research</title><addtitle>Pathol. Oncol. Res</addtitle><addtitle>PATHOL ONCOL RES</addtitle><addtitle>Pathol Oncol Res</addtitle><description>We aimed to analyze the expression of cell-cycle regulation markers – minichromosome maintenance protein 2 (MCM2), Ki-67, Cyclin-A and phosphohistone-H3 (PHH3) − in pre-treatment core-biopsy samples of breast carcinomas in correlation with known predictive and prognostic factors. Totally 52 core biopsy samples obtained prior to neoadjuvant therapy were analyzed. Immunohistochemistry was performed to analyze the expression of MCM2, Ki-67, Cyclin A and PHH3, which were correlated with the following clinicopathological parameters: clinical TNM, tumor grade, biological subtype, the presence of tumor infiltrating lymphocytes (TIL), pathological tumor response rate to the neoadjuvant therapy and patient survival. All investigated markers showed higher expression in high grade and in triple negative tumors (
p
< 0.01 and
p
< 0.05, respectively). Hormone receptor negative tumors showed significantly higher expression of Ki-67 (p < 0.01), MCM2 (p < 0.01) and Cyclin A (p < 0.01) than hormone receptor positive ones. Tumors with increased TIL showed significantly higher Ki-67 expression (
p
= 0.04). Pattern analysis suggested that novel cell-cycle marker-based subgrouping reveals predictive and prognostic potential. Tumors with high MCM2, Cyclin A or PHH3 expression showed significantly higher rate of pathological complete remission. Tumors with early relapse (progression-free survival ≤2 years) and shortened overall survival also show a higher rate of proliferation. Our cell cycle marker (Ki-67, MCM2, Cyclin A, PHH3) based testing could identify tumors with worse prognosis, but with a favorable response to primary systemic therapy. 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Tőkés, Anna-Mária ; Szentmártoni, Gyöngyvér ; Kiszner, Gergő ; Mühl, Dorottya ; Molnár, Béla Ákos ; Kulka, Janina ; Krenács, Tibor ; Dank, Magdolna</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c502t-7fccebe7a1978a6e38f6289867d53d283c6a51d441c1f9775d250afaed26811a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Biopsy</topic><topic>Breast cancer</topic><topic>Breast carcinoma</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - pathology</topic><topic>Cancer Research</topic><topic>Cell cycle</topic><topic>Cell Cycle - drug effects</topic><topic>Cell Cycle Proteins - analysis</topic><topic>Cell Cycle Proteins - drug effects</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Cyclin A</topic><topic>Female</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Immunology</topic><topic>Life Sciences & Biomedicine</topic><topic>Lymphocytes</topic><topic>Lymphocytes, Tumor-Infiltrating - drug effects</topic><topic>Lymphocytes, Tumor-Infiltrating - pathology</topic><topic>Medical prognosis</topic><topic>Middle Aged</topic><topic>Oncology</topic><topic>Original</topic><topic>Original Article</topic><topic>Pathology</topic><topic>Patients</topic><topic>Prognosis</topic><topic>Remission</topic><topic>Science & Technology</topic><topic>Survival</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tőkés, Tímea</creatorcontrib><creatorcontrib>Tőkés, Anna-Mária</creatorcontrib><creatorcontrib>Szentmártoni, Gyöngyvér</creatorcontrib><creatorcontrib>Kiszner, Gergő</creatorcontrib><creatorcontrib>Mühl, Dorottya</creatorcontrib><creatorcontrib>Molnár, Béla Ákos</creatorcontrib><creatorcontrib>Kulka, Janina</creatorcontrib><creatorcontrib>Krenács, Tibor</creatorcontrib><creatorcontrib>Dank, Magdolna</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Pathology oncology research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tőkés, Tímea</au><au>Tőkés, Anna-Mária</au><au>Szentmártoni, Gyöngyvér</au><au>Kiszner, Gergő</au><au>Mühl, Dorottya</au><au>Molnár, Béla Ákos</au><au>Kulka, Janina</au><au>Krenács, Tibor</au><au>Dank, Magdolna</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prognostic and Clinicopathological Correlations of Cell Cycle Marker Expressions before and after the Primary Systemic Therapy of Breast Cancer</atitle><jtitle>Pathology oncology research</jtitle><stitle>Pathol. Oncol. Res</stitle><stitle>PATHOL ONCOL RES</stitle><addtitle>Pathol Oncol Res</addtitle><date>2020-07-01</date><risdate>2020</risdate><volume>26</volume><issue>3</issue><spage>1499</spage><epage>1510</epage><pages>1499-1510</pages><issn>1219-4956</issn><eissn>1532-2807</eissn><abstract>We aimed to analyze the expression of cell-cycle regulation markers – minichromosome maintenance protein 2 (MCM2), Ki-67, Cyclin-A and phosphohistone-H3 (PHH3) − in pre-treatment core-biopsy samples of breast carcinomas in correlation with known predictive and prognostic factors. Totally 52 core biopsy samples obtained prior to neoadjuvant therapy were analyzed. Immunohistochemistry was performed to analyze the expression of MCM2, Ki-67, Cyclin A and PHH3, which were correlated with the following clinicopathological parameters: clinical TNM, tumor grade, biological subtype, the presence of tumor infiltrating lymphocytes (TIL), pathological tumor response rate to the neoadjuvant therapy and patient survival. All investigated markers showed higher expression in high grade and in triple negative tumors (
p
< 0.01 and
p
< 0.05, respectively). Hormone receptor negative tumors showed significantly higher expression of Ki-67 (p < 0.01), MCM2 (p < 0.01) and Cyclin A (p < 0.01) than hormone receptor positive ones. Tumors with increased TIL showed significantly higher Ki-67 expression (
p
= 0.04). Pattern analysis suggested that novel cell-cycle marker-based subgrouping reveals predictive and prognostic potential. Tumors with high MCM2, Cyclin A or PHH3 expression showed significantly higher rate of pathological complete remission. Tumors with early relapse (progression-free survival ≤2 years) and shortened overall survival also show a higher rate of proliferation. Our cell cycle marker (Ki-67, MCM2, Cyclin A, PHH3) based testing could identify tumors with worse prognosis, but with a favorable response to primary systemic therapy. The pattern of cell-cycle activity could also be useful for predicting early relapse, but our findings need to be further substantiated in larger patient cohorts.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>31446607</pmid><doi>10.1007/s12253-019-00726-w</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-5456-1706</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Antineoplastic Agents - therapeutic use Biomarkers, Tumor - analysis Biomedical and Life Sciences Biomedicine Biopsy Breast cancer Breast carcinoma Breast Neoplasms - drug therapy Breast Neoplasms - pathology Cancer Research Cell cycle Cell Cycle - drug effects Cell Cycle Proteins - analysis Cell Cycle Proteins - drug effects Cell Cycle Proteins - metabolism Cyclin A Female Humans Immunohistochemistry Immunology Life Sciences & Biomedicine Lymphocytes Lymphocytes, Tumor-Infiltrating - drug effects Lymphocytes, Tumor-Infiltrating - pathology Medical prognosis Middle Aged Oncology Original Original Article Pathology Patients Prognosis Remission Science & Technology Survival Tumors |
| title | Prognostic and Clinicopathological Correlations of Cell Cycle Marker Expressions before and after the Primary Systemic Therapy of Breast Cancer |
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