Clinicopathological Characterization and Prognostic Implication of SMAD4 Expression in Colorectal Carcinoma
Background SMAD family member 4 (SMAD4) has gained attention as a promising prognostic factor of colorectal cancer (CRC) as well as a key molecule to understand the tumorigenesis and progression of CRC. Methods We retrospectively analyzed 1,281 CRC cases immunohistochemically for their expression st...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Korean Society of Pathologists & the Korean Society for Cytopathology
2019-09-01
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| Series: | Journal of Pathology and Translational Medicine |
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| Online Access: | http://www.jpatholtm.org/upload/pdf/jptm-2019-06-07.pdf |
| _version_ | 1818598473639919616 |
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| author | Seung-Yeon Yoo Ji-Ae Lee Yunjoo Shin Nam-Yun Cho Jeong Mo Bae Gyeong Hoon Kang |
| author_facet | Seung-Yeon Yoo Ji-Ae Lee Yunjoo Shin Nam-Yun Cho Jeong Mo Bae Gyeong Hoon Kang |
| author_sort | Seung-Yeon Yoo |
| collection | DOAJ |
| description | Background SMAD family member 4 (SMAD4) has gained attention as a promising prognostic factor of colorectal cancer (CRC) as well as a key molecule to understand the tumorigenesis and progression of CRC. Methods We retrospectively analyzed 1,281 CRC cases immunohistochemically for their expression status of SMAD4, and correlated this status with clinicopathologic and molecular features of CRCs. Results A loss of nuclear SMAD4 was significantly associated with frequent lymphovascular and perineural invasion, tumor budding, fewer tumor-infiltrating lymphocytes, higher pT and pN category, and frequent distant metastasis. In contrast, tumors overexpressing SMAD4 showed a significant association with sporadic microsatellite instability. After adjustment for TNM stage, tumor differentiation, adjuvant chemotherapy, and lymphovascular invasion, the loss of SMAD4 was found to be an independent prognostic factor for worse 5-year progression-free survival (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.01 to 1.60; p=.042) and 7-year cancer-specific survival (HR, 1.45; 95% CI, 1.06 to 1.99; p=.022). Conclusions We confirmed the value of determining the loss of SMAD4 immunohistochemically as an independent prognostic factor for CRC in general. In addition, we identified some histologic and molecular features that might be clues to elucidate the role of SMAD4 in colorectal tumorigenesis and progression. |
| first_indexed | 2024-12-16T12:04:16Z |
| format | Article |
| id | doaj.art-3add61b7f3db4b73aa1511906451374d |
| institution | Directory Open Access Journal |
| issn | 2383-7837 2383-7845 |
| language | English |
| last_indexed | 2024-12-16T12:04:16Z |
| publishDate | 2019-09-01 |
| publisher | Korean Society of Pathologists & the Korean Society for Cytopathology |
| record_format | Article |
| series | Journal of Pathology and Translational Medicine |
| spelling | doaj.art-3add61b7f3db4b73aa1511906451374d2022-12-21T22:32:21ZengKorean Society of Pathologists & the Korean Society for CytopathologyJournal of Pathology and Translational Medicine2383-78372383-78452019-09-0153528929710.4132/jptm.2019.06.0716853Clinicopathological Characterization and Prognostic Implication of SMAD4 Expression in Colorectal CarcinomaSeung-Yeon Yoo0Ji-Ae Lee1Yunjoo Shin2Nam-Yun Cho3Jeong Mo Bae4Gyeong Hoon Kang5 Department of Pathology, Seoul National University Hospital, Seoul, Korea Department of Pathology, Seoul National University Hospital, Seoul, Korea Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea Department of Pathology, Seoul National University Hospital, Seoul, Korea Department of Pathology, Seoul National University Hospital, Seoul, KoreaBackground SMAD family member 4 (SMAD4) has gained attention as a promising prognostic factor of colorectal cancer (CRC) as well as a key molecule to understand the tumorigenesis and progression of CRC. Methods We retrospectively analyzed 1,281 CRC cases immunohistochemically for their expression status of SMAD4, and correlated this status with clinicopathologic and molecular features of CRCs. Results A loss of nuclear SMAD4 was significantly associated with frequent lymphovascular and perineural invasion, tumor budding, fewer tumor-infiltrating lymphocytes, higher pT and pN category, and frequent distant metastasis. In contrast, tumors overexpressing SMAD4 showed a significant association with sporadic microsatellite instability. After adjustment for TNM stage, tumor differentiation, adjuvant chemotherapy, and lymphovascular invasion, the loss of SMAD4 was found to be an independent prognostic factor for worse 5-year progression-free survival (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.01 to 1.60; p=.042) and 7-year cancer-specific survival (HR, 1.45; 95% CI, 1.06 to 1.99; p=.022). Conclusions We confirmed the value of determining the loss of SMAD4 immunohistochemically as an independent prognostic factor for CRC in general. In addition, we identified some histologic and molecular features that might be clues to elucidate the role of SMAD4 in colorectal tumorigenesis and progression.http://www.jpatholtm.org/upload/pdf/jptm-2019-06-07.pdfBiomarkerSMAD4Colorectal neoplasmsPrognosis |
| spellingShingle | Seung-Yeon Yoo Ji-Ae Lee Yunjoo Shin Nam-Yun Cho Jeong Mo Bae Gyeong Hoon Kang Clinicopathological Characterization and Prognostic Implication of SMAD4 Expression in Colorectal Carcinoma Journal of Pathology and Translational Medicine Biomarker SMAD4 Colorectal neoplasms Prognosis |
| title | Clinicopathological Characterization and Prognostic Implication of SMAD4 Expression in Colorectal Carcinoma |
| title_full | Clinicopathological Characterization and Prognostic Implication of SMAD4 Expression in Colorectal Carcinoma |
| title_fullStr | Clinicopathological Characterization and Prognostic Implication of SMAD4 Expression in Colorectal Carcinoma |
| title_full_unstemmed | Clinicopathological Characterization and Prognostic Implication of SMAD4 Expression in Colorectal Carcinoma |
| title_short | Clinicopathological Characterization and Prognostic Implication of SMAD4 Expression in Colorectal Carcinoma |
| title_sort | clinicopathological characterization and prognostic implication of smad4 expression in colorectal carcinoma |
| topic | Biomarker SMAD4 Colorectal neoplasms Prognosis |
| url | http://www.jpatholtm.org/upload/pdf/jptm-2019-06-07.pdf |
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