title: p16 expression differentiates high-risk gastrointestinal stromal tumor and predicts poor outcome.
abstract: 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."
authors.affiliation: Clinic of General, Visceral and Transplantation Surgery, University Hospital Ulm, Ulm, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schmieder
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wolf
authors.forename: Bettina
authors.initials: B
authors.lastname: Danner
authors.forename: Susanne
authors.initials: S
authors.lastname: Stoehr
authors.forename: Markus S
authors.initials: MS
authors.lastname: Juchems
authors.forename: Peter
authors.initials: P
authors.lastname: Wuerl
authors.forename: Doris
authors.initials: D
authors.lastname: Henne-Bruns
authors.forename: Uwe
authors.initials: U
authors.lastname: Knippschild
authors.forename: Cornelia
authors.initials: C
authors.lastname: Hasel
authors.forename: Klaus
authors.initials: K
authors.lastname: Kramer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003937:Diagnosis, Differential; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D019942:Genes, p16; D006801:Humans; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D009362:Neoplasm Metastasis; D011237:Predictive Value of Tests; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors; D055815:Young Adult