Prognostic significance of mitotic and apoptotic index and the DNA cytometry in head and neck cancer.
The lack of suitable criteria to predict the response to chemo- and or radiotherapy for individual patients with squamous cell carcinoma of the head and neck (HNSCC) remains still a major problem. This study was conducted to analyze prognostic significance of mitotic and apoptotic index and the DNA flow cytometric analysis of HNSCC to the recurrence-free survival time and to the overall survival. The analysis was carried out in a set of 56 patients suffering from carcinoma of the pharynx and supraglottis. Most patients (96.7%) underwent neoadjuvant chemotherapy, followed by surgery and postoperative irradiation. Besides routine examinations, flow cytometric analysis was performed, as well as p53 and Ki-67 markers and mitotic and apoptotic index were established by means of immunohistochemistry. Event-free survival (EFS) and overall survival (OS) were accepted as primary endpoints for the prognostic analyses. All the examined potential markers entered standard Kaplan-Meier survival analysis and Cox regression modeling. Statistical significance of prognostic factors was first examined in univariate models and all the parameters subsequently entered multivariate models. The analyses revealed significant prognostic position of advanced clinical stage (III+IV) and increased proliferative activity as primary risk factors (p<0.01) that typically positively correlate with increased mitotic activity and G2/M cell fraction. Better survival results obtained for grade 3-4 as compared to grade 1-2 were caused by molecular parameters that make these samples similar to less risk cases. Cytokinetic parameters and proliferation activity were found as important predictors of the second level (after recognizing stage, grade and DNA status of the tumor). Multivariate combination of these markers contributed namely to the prognosis of early risk event: a ratio S phase cell fraction/G2M cell fraction was found to be the key prognostic factor (p<0.01). Early risk events are associated with increased mitotic activity, decreased apoptic rate, decreased S phase cell fraction and significantly increased G2/M fraction.
Smilek
P
P
Faculty of Medicine, Masaryk University Hospital, Clinic of Otorhinolaryngology and Head and Neck Surgery, 63500 Brno, Czech Republik. smilek@med.muni.cz
Dusek
L
L
Veselý
K
K
Rottenberg
J
J
Kostrica
R
R
D000328:Adult; D000368:Aged; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D004247:DNA / Q000032:analysis*; D018572:Disease-Free Survival; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D011003:Ploidies; D011379:Prognosis; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D004247:DNA