title: p16 expression predicts neoadjuvant tumor necrosis in osteosarcomas: reappraisal with a larger series using whole sections.
abstract: The presence of greater than or equal to 90% necrosis after neoadjuvant chemotherapy is a favorable prognostic factor in osteosarcomas. A recent study using tissue microarrays of 40 conventional osteosarcomas showed that p16 expression independently predicted the necrotic response to neoadjuvant chemotherapy. In this study, we investigated this finding using whole sections in a larger group of osteosarcomas. Cases of 83 patients who had pretreatment biopsies and received neoadjuvant chemotherapy and surgical resection were collected from 3 reference hospital archives. Age, sex, tumor size, tumor subtype, location, and percentage of tumor necrosis were recorded; 4-μm sections from pretreatment biopsies were stained for p16. More than 30% strong nuclear staining was regarded as positive. The median age was 17 years (5-68 years), and male/female ratio was 2.3. The mean tumor diameter was 9.9 cm (2-30 cm). Tumors were most commonly of the osteoblastic type (60%) and located at the femur (47%). p16 positivity was seen in 66% of the patients. The median pathologic necrosis was 65%, and 39% of the patients responded favorably (≥%90 necrosis) to neoadjuvant therapy. In univariate analysis, p16 expression significantly correlated with greater than or equal to 90% response (P = .022). On multivariate analysis, p16 expression (odds ratio [OR], 7.71; P = .008), female sex (OR, 8.62; P = .006), and smaller tumor size (OR, 0.86; P = .023) were independent predictors of favorable response to neoadjuvant chemotherapy. We confirmed the finding that p16 expression predicts postchemotherapy necrotic response in conventional osteosarcomas.
authors.affiliation: Department of Pathology, Hacettepe University School of Medicine, 06230 Ankara, Turkey. Electronic address: dokemal@hotmail.com.
authors.forename: Kemal
authors.initials: K
authors.lastname: Kosemehmetoglu
authors.affiliation: Department of Pathology, Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, 06200 Ankara, Turkey.
authors.forename: Fisun
authors.initials: F
authors.lastname: Ardic
authors.affiliation: Department of Pathology, Gulhane Military Medical Academy, 06010 Ankara, Turkey.
authors.forename: Yildirim
authors.initials: Y
authors.lastname: Karslioglu
authors.affiliation: Department of Pathology, Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, 06200 Ankara, Turkey.
authors.forename: Olcay
authors.initials: O
authors.lastname: Kandemir
authors.affiliation: Department of Pathology, Gulhane Military Medical Academy, 06010 Ankara, Turkey.
authors.forename: Ayhan
authors.initials: A
authors.lastname: Ozcan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D001859:Bone Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008867:Microtomy; D008875:Middle Aged; D015999:Multivariate Analysis; D009336:Necrosis; D020360:Neoadjuvant Therapy; D016017:Odds Ratio; D012516:Osteosarcoma / Q000737:chemistry* / Q000188:drug therapy* / Q000473:pathology; D011237:Predictive Value of Tests; D012307:Risk Factors; D012737:Sex Factors; D016896:Treatment Outcome; D047368:Tumor Burden; D014421:Turkey; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16
keywords: CDKN2A; Immunohistochemistry; Neoadjuvant chemotherapy; Osteogenic sarcoma; Pathologic necrosis; Prognosis