Automated Quantitative Analysis of p53, Cyclin D1, Ki67 and pERK Expression in Breast Carcinoma Does Not Differ from Expert Pathologist Scoring and Correlates with Clinico-Pathological Characteristics
There is critical need for improved biomarker assessment platforms which integrate traditional pathological parameters (TNM stage, grade and ER/PR/HER2 status) with molecular profiling, to better define prognostic subgroups or systemic treatment response. One roadblock is the lack of semi-quantitati...
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| Format: | Article |
| Language: | English |
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MDPI AG
2012-07-01
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| Series: | Cancers |
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| Online Access: | http://www.mdpi.com/2072-6694/4/3/725 |
| _version_ | 1797715405519716352 |
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| author | Yolanda Madarnas Sandip K. SenGupta Bruce E. Elliott Jeremy Squire Leda H. Raptis Ashish B. Rajput Andrew G. Day Waheed Sangrar Sonal Varma Jamaica D. Cass |
| author_facet | Yolanda Madarnas Sandip K. SenGupta Bruce E. Elliott Jeremy Squire Leda H. Raptis Ashish B. Rajput Andrew G. Day Waheed Sangrar Sonal Varma Jamaica D. Cass |
| author_sort | Yolanda Madarnas |
| collection | DOAJ |
| description | There is critical need for improved biomarker assessment platforms which integrate traditional pathological parameters (TNM stage, grade and ER/PR/HER2 status) with molecular profiling, to better define prognostic subgroups or systemic treatment response. One roadblock is the lack of semi-quantitative methods which reliably measure biomarker expression. Our study assesses reliability of automated immunohistochemistry (IHC) scoring compared to manual scoring of five selected biomarkers in a tissue microarray (TMA) of 63 human breast cancer cases, and correlates these markers with clinico-pathological data. TMA slides were scanned into an Ariol Imaging System, and histologic (H) scores (% positive tumor area x staining intensity 0–3) were calculated using trained algorithms. H scores for all five biomarkers concurred with pathologists’ scores, based on Pearson correlation coefficients (0.80–0.90) for continuous data and Kappa statistics (0.55–0.92) for positive vs. negative stain. Using continuous data, significant association of pERK expression with absence of LVI (<em>p</em> = 0.005) and lymph node negativity (<em>p</em> = 0.002) was observed. p53 over-expression, characteristic of dysfunctional p53 in cancer, and Ki67 were associated with high grade (<em>p</em> = 0.032 and 0.0007, respectively). Cyclin D1 correlated inversely with ER/PR/HER2-ve (triple negative) tumors (<em>p</em> = 0.0002). Thus automated quantitation of immunostaining concurs with pathologists’ scoring, and provides meaningful associations with clinico-pathological data. |
| first_indexed | 2024-03-12T08:06:17Z |
| format | Article |
| id | doaj.art-dbb494e1d0e54f59b0f7f51dbd67775c |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T08:06:17Z |
| publishDate | 2012-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-dbb494e1d0e54f59b0f7f51dbd67775c2023-09-02T19:29:29ZengMDPI AGCancers2072-66942012-07-014372574210.3390/cancers4030725Automated Quantitative Analysis of p53, Cyclin D1, Ki67 and pERK Expression in Breast Carcinoma Does Not Differ from Expert Pathologist Scoring and Correlates with Clinico-Pathological CharacteristicsYolanda MadarnasSandip K. SenGuptaBruce E. ElliottJeremy SquireLeda H. RaptisAshish B. RajputAndrew G. DayWaheed SangrarSonal VarmaJamaica D. CassThere is critical need for improved biomarker assessment platforms which integrate traditional pathological parameters (TNM stage, grade and ER/PR/HER2 status) with molecular profiling, to better define prognostic subgroups or systemic treatment response. One roadblock is the lack of semi-quantitative methods which reliably measure biomarker expression. Our study assesses reliability of automated immunohistochemistry (IHC) scoring compared to manual scoring of five selected biomarkers in a tissue microarray (TMA) of 63 human breast cancer cases, and correlates these markers with clinico-pathological data. TMA slides were scanned into an Ariol Imaging System, and histologic (H) scores (% positive tumor area x staining intensity 0–3) were calculated using trained algorithms. H scores for all five biomarkers concurred with pathologists’ scores, based on Pearson correlation coefficients (0.80–0.90) for continuous data and Kappa statistics (0.55–0.92) for positive vs. negative stain. Using continuous data, significant association of pERK expression with absence of LVI (<em>p</em> = 0.005) and lymph node negativity (<em>p</em> = 0.002) was observed. p53 over-expression, characteristic of dysfunctional p53 in cancer, and Ki67 were associated with high grade (<em>p</em> = 0.032 and 0.0007, respectively). Cyclin D1 correlated inversely with ER/PR/HER2-ve (triple negative) tumors (<em>p</em> = 0.0002). Thus automated quantitation of immunostaining concurs with pathologists’ scoring, and provides meaningful associations with clinico-pathological data.http://www.mdpi.com/2072-6694/4/3/725breast cancerp53/cyclin D1/Ki67/pERKtissue microarrayautomated image analysisclinico-pathological parameters |
| spellingShingle | Yolanda Madarnas Sandip K. SenGupta Bruce E. Elliott Jeremy Squire Leda H. Raptis Ashish B. Rajput Andrew G. Day Waheed Sangrar Sonal Varma Jamaica D. Cass Automated Quantitative Analysis of p53, Cyclin D1, Ki67 and pERK Expression in Breast Carcinoma Does Not Differ from Expert Pathologist Scoring and Correlates with Clinico-Pathological Characteristics Cancers breast cancer p53/cyclin D1/Ki67/pERK tissue microarray automated image analysis clinico-pathological parameters |
| title | Automated Quantitative Analysis of p53, Cyclin D1, Ki67 and pERK Expression in Breast Carcinoma Does Not Differ from Expert Pathologist Scoring and Correlates with Clinico-Pathological Characteristics |
| title_full | Automated Quantitative Analysis of p53, Cyclin D1, Ki67 and pERK Expression in Breast Carcinoma Does Not Differ from Expert Pathologist Scoring and Correlates with Clinico-Pathological Characteristics |
| title_fullStr | Automated Quantitative Analysis of p53, Cyclin D1, Ki67 and pERK Expression in Breast Carcinoma Does Not Differ from Expert Pathologist Scoring and Correlates with Clinico-Pathological Characteristics |
| title_full_unstemmed | Automated Quantitative Analysis of p53, Cyclin D1, Ki67 and pERK Expression in Breast Carcinoma Does Not Differ from Expert Pathologist Scoring and Correlates with Clinico-Pathological Characteristics |
| title_short | Automated Quantitative Analysis of p53, Cyclin D1, Ki67 and pERK Expression in Breast Carcinoma Does Not Differ from Expert Pathologist Scoring and Correlates with Clinico-Pathological Characteristics |
| title_sort | automated quantitative analysis of p53 cyclin d1 ki67 and perk expression in breast carcinoma does not differ from expert pathologist scoring and correlates with clinico pathological characteristics |
| topic | breast cancer p53/cyclin D1/Ki67/pERK tissue microarray automated image analysis clinico-pathological parameters |
| url | http://www.mdpi.com/2072-6694/4/3/725 |
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