Alterations in the Expression of p53, KLF4, and p21 in Neuroendocrine Lung Tumors

Context.-Neuroendocrine lung neoplasms are a heterogeneous group of tumors with different clinical behavior and prognosis. Objectives.-To evaluate the expression of p53, KLF4, and p21 in neuroendocrine lung neoplasms and to analyze the influence that expression has on the prognosis of those tumors. Design.-All neuroendocrine lung neoplasms (N = 109) resected in our institution were reviewed, with the collection of histologic slides and paraffin blocks of 47 typical carcinoids (43%), 9 atypical carcinoids (8%), 35 large cell neuroendocrine carcinomas (32%), and 18 small cell lung carcinomas (17%), as well as 10 tumorlets (100%). Four tissue microarrays were performed. Followup was assessed in all cases (119 of 119; 100%). Results.-p53 protein immunostaining results were negative in both the tumorlets and typical carcinoids and were overexpressed in 11% (1 of 9) of the atypical carcinoids and in 68% (36 of 53) of the carcinomas. KLF4 results were positive in all tumorlets (10 of 10; 100%), 32% (15 of 47) of the typical carcinoids, 44% (4 of 9) of the atypical carcinoids, and 62% (33 of 53) of the carcinomas. p21 expression did not differ among the groups. The lack of KLF4 and p21 expression was associated with an accumulation of aggressive features in typical carcinoids (P = .04 and P = .004, respectively, Fisher exact test). Conclusions.-p53, KLF4, and p21 showed altered expression patterns in pulmonary neuroendocrine neoplasms. Lack of KLF4 and p21 expression was associated with accumulation of aggressive features in typical carcinoids.