Alterations in the expression of p53, KLF4, and p21 in neuroendocrine lung tumors

Arch Pathol Lab Med. 2014 Jul;138(7):936-42. doi: 10.5858/arpa.2013-0119-OA.

Abstract

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. Follow-up 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.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Carcinoid Tumor / metabolism
  • Carcinoid Tumor / pathology
  • Carcinoma, Neuroendocrine / metabolism
  • Carcinoma, Neuroendocrine / pathology
  • Carcinoma, Small Cell / metabolism
  • Carcinoma, Small Cell / pathology
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / metabolism*
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Neuroendocrine Tumors / metabolism*
  • Neuroendocrine Tumors / pathology
  • Prognosis
  • Tissue Array Analysis
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Biomarkers, Tumor
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • KLF4 protein, human
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • TP53 protein, human
  • Tumor Suppressor Protein p53