p16 Expression Differentiates High-Risk Gastrointestinal Stromal Tumor and Predicts Poor Outcome
Gastrointestinal stromal tumors (GISTs) are characterized by alterations in genes involved in cell cycle regulation. Although p16 (INK4A) have been extensively investigated in GISTs, there are still discrepancies regarding its prognostic value. Therefore, we evaluated the clinical occurrence, diagno...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2008-10-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558608801066 |
| _version_ | 1818520818534055936 |
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| author | Michael Schmieder Sebastian Wolf Bettina Danner Susanne Stoehr Markus S. Juchems Peter Wuerl Doris Henne-Bruns Uwe Knippschild Cornelia Hasel Klaus Kramer |
| author_facet | Michael Schmieder Sebastian Wolf Bettina Danner Susanne Stoehr Markus S. Juchems Peter Wuerl Doris Henne-Bruns Uwe Knippschild Cornelia Hasel Klaus Kramer |
| author_sort | Michael Schmieder |
| collection | DOAJ |
| description | Gastrointestinal stromal tumors (GISTs) are characterized by alterations in genes involved in cell cycle regulation. Although p16 (INK4A) have been extensively investigated in GISTs, there are still discrepancies regarding its prognostic value. Therefore, we evaluated the clinical occurrence, diagnostic and prognostic value of p16 staining in GIST. One hundred one patients (54 women and 47 men) with a mean age of 64.1 years (range, 17–94 years) were surgically treated for a GIST within a 10-year period. Of these patients, 28 (28%) were affected by metastases (mean follow-up, 4.5 years). In 36 patients (36%), GIST occurred coincidentally with other malignancies. Expression of c-kit was confirmed in 97 GIST patients (96%). In patients with high-risk GIST, the expression of p16 expression was highly predictive for poor prognosis, i.e., the development of recurrence or metastases (P = .006) and poor survival (P = .004). In addition, the expression of p16 was highly predictive for reduction of the survival in patients who were affected by metastases or recurrence (P = .041). The disease-specific and disease-free 1-, 3-, and 5-year survival rate was 96%, 90%, and 85% and 81%, 77%, and 72%, respectively. Primary tumor state, tumor size, and high-risk classification were confirmed as relevant predictors for unfavorable prognosis in GIST (P < .001). Our results indicate that in high-risk GIST and in patients with recurrence or metastases, the expression of p16 is highly predictive for poor outcome. Thus, in addition to high-risk classification, p16 expression might be an indicator for “very high risk GIST.” |
| first_indexed | 2024-12-11T01:42:45Z |
| format | Article |
| id | doaj.art-cee15cf9ecde45fd829142c59d73edc3 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-11T01:42:45Z |
| publishDate | 2008-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-cee15cf9ecde45fd829142c59d73edc32022-12-22T01:24:59ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022008-10-0110101154116210.1593/neo.08646p16 Expression Differentiates High-Risk Gastrointestinal Stromal Tumor and Predicts Poor OutcomeMichael Schmieder0Sebastian Wolf1Bettina Danner2Susanne Stoehr3Markus S. Juchems4Peter Wuerl5Doris Henne-Bruns6Uwe Knippschild7Cornelia Hasel8Klaus Kramer9Clinic of General, Visceral and Transplantation Surgery, University Hospital Ulm, Ulm, GermanyClinic of General, Visceral and Transplantation Surgery, University Hospital Ulm, Ulm, GermanyInstitutes of Biometrics, University Hospital Ulm, Ulm, GermanyInstitutes of Biometrics, University Hospital Ulm, Ulm, GermanyDepartment of Diagnostic Radiology, University Hospital Ulm, Ulm, GermanyClinic of General, Visceral and Transplantation Surgery, University Hospital Ulm, Ulm, GermanyClinic of General, Visceral and Transplantation Surgery, University Hospital Ulm, Ulm, GermanyClinic of General, Visceral and Transplantation Surgery, University Hospital Ulm, Ulm, GermanyDepartment of Pathology, University Hospital Ulm, Ulm, GermanyClinic of General, Visceral and Transplantation Surgery, University Hospital Ulm, Ulm, GermanyGastrointestinal stromal tumors (GISTs) are characterized by alterations in genes involved in cell cycle regulation. Although p16 (INK4A) have been extensively investigated in GISTs, there are still discrepancies regarding its prognostic value. Therefore, we evaluated the clinical occurrence, diagnostic and prognostic value of p16 staining in GIST. One hundred one patients (54 women and 47 men) with a mean age of 64.1 years (range, 17–94 years) were surgically treated for a GIST within a 10-year period. Of these patients, 28 (28%) were affected by metastases (mean follow-up, 4.5 years). In 36 patients (36%), GIST occurred coincidentally with other malignancies. Expression of c-kit was confirmed in 97 GIST patients (96%). In patients with high-risk GIST, the expression of p16 expression was highly predictive for poor prognosis, i.e., the development of recurrence or metastases (P = .006) and poor survival (P = .004). In addition, the expression of p16 was highly predictive for reduction of the survival in patients who were affected by metastases or recurrence (P = .041). The disease-specific and disease-free 1-, 3-, and 5-year survival rate was 96%, 90%, and 85% and 81%, 77%, and 72%, respectively. Primary tumor state, tumor size, and high-risk classification were confirmed as relevant predictors for unfavorable prognosis in GIST (P < .001). Our results indicate that in high-risk GIST and in patients with recurrence or metastases, the expression of p16 is highly predictive for poor outcome. Thus, in addition to high-risk classification, p16 expression might be an indicator for “very high risk GIST.”http://www.sciencedirect.com/science/article/pii/S1476558608801066 |
| spellingShingle | Michael Schmieder Sebastian Wolf Bettina Danner Susanne Stoehr Markus S. Juchems Peter Wuerl Doris Henne-Bruns Uwe Knippschild Cornelia Hasel Klaus Kramer p16 Expression Differentiates High-Risk Gastrointestinal Stromal Tumor and Predicts Poor Outcome Neoplasia: An International Journal for Oncology Research |
| title | p16 Expression Differentiates High-Risk Gastrointestinal Stromal Tumor and Predicts Poor Outcome |
| title_full | p16 Expression Differentiates High-Risk Gastrointestinal Stromal Tumor and Predicts Poor Outcome |
| title_fullStr | p16 Expression Differentiates High-Risk Gastrointestinal Stromal Tumor and Predicts Poor Outcome |
| title_full_unstemmed | p16 Expression Differentiates High-Risk Gastrointestinal Stromal Tumor and Predicts Poor Outcome |
| title_short | p16 Expression Differentiates High-Risk Gastrointestinal Stromal Tumor and Predicts Poor Outcome |
| title_sort | p16 expression differentiates high risk gastrointestinal stromal tumor and predicts poor outcome |
| url | http://www.sciencedirect.com/science/article/pii/S1476558608801066 |
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