Ki‐67 (MIB1), p53, and Lewis‐X (LeuM1) as Prognostic Factors of Recurrence in T1 and T2 Laryngeal Carcinoma

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Abstract
Objectives Recently published data suggest a prognostic value of immunohistochemical proliferation markers for limited laryngeal carcinoma. Previous studies have reported contrasting findings on this issue. In this context, different treatment modalities may be responsible for contradictory findings. To study the relationship between proliferative activity—expressed by the immunohistochemical labeling index of proliferation-associated markers Ki-67 (MIB1), Lewis-X (LeuM1), and proliferating cell nuclear antigen (PCNA) and by p53 status—and treatment failure in a matched-pair study on recurrent and nonrecurrent T1 and T2 glottic carcinoma having received primary transoral laser surgery. Methods Twenty-one patients with tumor recurrence were randomly selected and matched with 26 patients with nonrecurrent disease regarding histopathological grading and age. MIB1 staining was used to determine the Ki-67 labeling inde-, and LeuM1 staining for detecting the Lewis-X antigen; immunohistochemistry determined the p53 status and PCNA labeling inde-. Results The Ki-67 labeling index was significantly (P = .001) higher in tumors from patients who had treatment failure (mean = 20.02%) than in patients who did not fail treatment (“nonfailures”) (mean = 9.95%). Carcinoma with a Ki-67 (MIB1) labeling index above the median (15%) of the general study population showed a mean time to relapse of 23 months (n = 21), compared with 50 months for cases (n = 26) below the median (P = .016). PCNA labeling index correlated less impressively with tumor recurrence (mean = 28.59% for treatment failures, mean = 21.75% for nonfailures, P = .022). Positive detection of the Lewis-X antigen was significantly associated with recurrence (P = .015) and time to relapse (P = .006). Status of p53 was not a significant prognostic factor. Conclusion The Ki-67 (MIB1) labeling index may be associated with early relapse of limited laryngeal carcinoma treated with transoral laser surgery. Since the prognostic relevance of Ki-67 seems to be different for radiological and surgical concepts of treatment, Ki-67 might become useful as criterion of therapy selection. The Lewis-X antigen, for the first time used on laryngeal carcinoma, seems to be a strong prognostic marker deserving further investigations.