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

TLDR

The study evaluated p63 and CK5/6 as immunohistochemical markers to differentiate poorly differentiated metastatic carcinomas of unknown primary site. The authors examined 73 squamous cell carcinomas from lung, head/neck, esophagus, cervix, and anal canal, 141 non‑squamous carcinomas, 20 urothelial carcinomas, and 14 malignant mesotheliomas for p63 and CK5/6 expression. Positive coexpression of p63 and CK5/6 was highly specific (up to 99%) for squamous cell carcinomas, with a sensitivity of 77% (66% when requiring >50% positive cells), and all mesotheliomas were negative, indicating that dual positivity strongly predicts a squamous epithelial primary.

Abstract

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.