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Value of p63 and Cytokeratin 5/6 as Immunohistochemical Markers for the Differential Diagnosis of Poorly Differentiated and Undifferentiated Carcinomas

Olaf Kaufmann MD, Ellen Fietze MD, Jörg Mengs, Manfred Dietel MD
DOI: http://dx.doi.org/10.1309/21TW-2NDG-JRK4-PFJX 823-830 First published online: 1 December 2001


To facilitate the differential diagnosis of poorly differentiated metastatic carcinomas of unknown primary site, we evaluated p63 and cytokeratin (CK) 5/6 as immunohistochemical markers for squamous cell carcinomas. The study cases were as follows: squamous cell carcinoma of the lungs, head/neck, esophagus, cervix uteri, or anal canal, 73; non–squamous cell carcinomas of various primary sites, 141; and urothelial carcinoma, 20. We also tested 14 malignant mesotheliomas.

Immunoreactivity for p63 was as follows: squamous cell carcinomas, 59 (81%); urothelial carcinoma, 14 (70%), most often with diffuse staining patterns; non–squamous cell carcinomas, 20 (14.2%), resulting in a specificity of 0.86 of p63 for squamous cell carcinomas. Coexpression of p63 and CK5/6 had a sensitivity of 0.77 and a specificity of 0.96 for squamous cell carcinomas. Increasing the minimal criterion of positive immunostaining for both markers to more than 50% of immunoreactive tumor cells resulted in a specificity of 0.99, although the sensitivity diminished to 0.66. All malignant mesotheliomas were negative for p63.

Our data suggest that positive immunostaining for both p63 and CK5/6 in poorly differentiated metastatic carcinomas is highly predictive of a primary tumor of squamous epithelial origin.

Key Words:
  • p63
  • Cytokeratin 5/6
  • Poorly differentiated carcinomas
  • Immunohistochemistry