title: Nuclear DNA content, an adjunct to p53 and Ki-67 as a marker of resistance to radiation therapy in oral cavity and pharyngeal squamous cell carcinoma.
abstract: Factors of prognosis and radioresistance in oral cavity and pharyngeal squamous cell carcinoma (OCPSCC) are limited. In the present study, the usefulness of tumor DNA content in predicting radioresistance in patients with OCPSCC has been investigated. Radioresistance has been defined as local recurrence or tumor persistence after radiation therapy. DNA-ploidy analysis was performed by static cytometry on smears of cell suspensions obtained from formalin-fixed paraffin-embedded material and stained with Feulgen. DNA-ploidy was correlated with the proliferation rate (Ki-67) and p53 protein accumulation obtained by immunohistochemistry. The follow-up of patients ranged from 8 to 62 months. Radioresistance was more common in non-diploid tumors; 14/28 (50%) non-diploid tumors recurred, whereas only 3 (10.7%) out of 28 diploid tumors had local failure (P=0.0019). Proliferation rate and p53 accumulation, evaluated by immunohistochemistry, also added prognostic information. Twelve out of 14 failures were from non-diploid tumors with a low proliferation rate (Ki-67<20%), whereas none of 20 p53-negative diploid tumors developed recurrences. This study showed that non-diploid tumors responded poorly to radiotherapy. DNA content appeared, therefore, as a significant prognostic marker for the evaluation of OCPSCC in patients receiving radiation therapy. This study also showed that DNA content adds information to p53 accumulation and the proliferation rate (Ki-67) for the purposes of determining patient management.
authors.affiliation: Laboratoire de Pathobiologie Orale, Nice, France. raybaud@unice.fr
authors.forename: H
authors.initials: H
authors.lastname: Raybaud
authors.forename: A
authors.initials: A
authors.lastname: Fortin
authors.forename: I
authors.initials: I
authors.lastname: Bairati
authors.forename: R
authors.initials: R
authors.lastname: Morency
authors.forename: R A
authors.initials: RA
authors.lastname: Monteil
authors.forename: B
authors.initials: B
authors.lastname: Têtu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001918:Brachytherapy; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D002455:Cell Division; D004396:Coloring Agents; D004273:DNA, Neoplasm / Q000032:analysis*; D004171:Diploidy; D005260:Female; D005500:Follow-Up Studies; D005544:Forecasting; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009367:Neoplasm Staging; D010610:Pharyngeal Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D011003:Ploidies; D011379:Prognosis; D011836:Radiation Tolerance; D011879:Radiotherapy Dosage; D012394:Rosaniline Dyes; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D004396:Coloring Agents; D004273:DNA, Neoplasm; C007722:Feulgen stain; D019394:Ki-67 Antigen; D012394:Rosaniline Dyes; D016159:Tumor Suppressor Protein p53