Prognostic significance of Ki-67 (MIB1), PCNA and p53 in cancer of the oropharynx and oral cavity

Up to now results concerning the prognostic value of tumor proliferation ma rkers in squamous cell head and neck carcinoma have been equivocal. Beside biological reasons, different treatment modalities are hypothetically respo nsible for contradictory findings. The aim of this study was to investigate the relationship between proliferative capacity, represented by the immuno histochemical labeling index of proliferation markers Ki-67, PCNA and p53 s tatus, and treatment failure in a matched-pair study design of recurrent an d non-recurrent carcinoma initially treated with primary surgery combined w ith curative post-operative radiation. From a group of 239 patients with T1 -T3 carcinoma of the oropharynx or oral cavity, 28 patients with recurrent disease were selected and matched with 28 patients with non-recurrent disea se regarding stage and location of tumor as well as age and therapy. All pa tients received primary surgery combined with post-operative radiation. Imm unohistochemistry determined the p53 status and the PCNA and MIBI (Ki-67) l abeling index. The Ki-67 labeling index was significantly (p = 0.032) highe r in tumors from patients suffering from treatment failure (mean = 59.1%) t han in non-failures (mean = 50.5%). Carcinoma with a Ki-67 (MIB1) labeling index above the median (53.7%) of the general study population showed a mea n time to relapse of 45 months (n = 25), whereas mean time-to-relapse was 6 1.7 months for those cases (n = 31) below the median of the general study p opulation (p = 0.029). The PCNA labeling index did not correlate significan tly with tumor recurrence (mean = 50.2% for treatment failures, 45% for non -failures, p = 0.31), nor with time-to-relapse (p = 0.26). Forty-six percen t of tumors showed p53 over-expression. However, there was no significant c orrelation between p53 over-expression and tumor recurrence or time-to-rela pse. We present the largest series of oropharyngeal and oral cavity carcino ma investigated by immunohistochemistry in a controlled study. We conclude that a high Ki-67 labeling index is an indicator for treatment failure in t hese patients. Like other investigations for different head and neck subsit es, we found no relationship between p53 or PCNA status and tumor prognosis . Our data, obtained from a group of patients treated with a combination of surgery and post-operative irradiation, show that for squamous cell carcin oma of the oropharynx and oral cavity the detection of Ki-67 is an unfavora ble prognostic factor. (C) 1999 Elsevier Science Ltd. All rights reserved.