Value of p63 and cytokeratin 5/6 as immunohistochemical markers for the differential diagnosis of poorly differentiated and undifferentiated carcinomas

Our plain-English summary of Value of p63 and cytokeratin 5/6 as immunohistochemical markers for the differential diagnosis of poorly differentiated and undifferentiated carcinomas, by O. Kaufmann, E. Fietze, J. Mengs, et al (American Journal of Clinical Pathology, 2001).

The study

• Authors: O. Kaufmann, E. Fietze, J. Mengs, M. Dietel
• Journal: American Journal of Clinical Pathology
• Published: 2001;116(6):823-30
• Cited by: 226 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

In plain English

This study tested whether two tissue stains, p63 and cytokeratin 5/6 (CK5/6), identify squamous cell carcinomas among poorly differentiated or undifferentiated carcinomas. The authors used archived samples from Charité University Hospital, Berlin: 73 squamous cell, 141 non–squamous cell and 20 urothelial carcinomas, and 14 malignant mesotheliomas. Asbestos exposure was not studied. A case counted as positive when at least moderate staining appeared in more than 10% of tumor cells. p63 stained 59 of 73 squamous cell carcinomas (81%) and 20 of 141 non–squamous cell carcinomas (14.2%). No mesothelioma was p63-positive; all 14 were CK5/6-positive. Both stains were positive in 56 of 73 squamous cell carcinomas (sensitivity 0.77) and in 5 of 141 non–squamous cell carcinomas (specificity 0.96). This comparison excluded urothelial carcinomas and mesotheliomas. With both stains required in more than 50% of cells, sensitivity was 0.66 (48 of 73) and specificity 0.99 (1 of 141 non–squamous cell carcinomas positive). The authors concluded that p63 can distinguish pleural or peritoneal metastases of nonkeratinizing squamous cell carcinomas from primary solid malignant mesotheliomas. They did not test rarer tumors that also express p63.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Diagnostic immunohistochemistry study of archived pathology specimens
• Who was studied: Archived tumor samples from the surgical pathology files of Charité University Hospital, Berlin, Germany. The samples were 73 poorly differentiated squamous cell carcinomas, 141 non–squamous cell carcinomas, 20 urothelial carcinomas and 14 malignant mesotheliomas. The mesotheliomas were 13 primary tumors and 1 metastasis; 10 were pleural, 1 pericardial and 3 peritoneal; 10 were epithelioid and 4 biphasic. Study years were not stated.
• Exposure: No asbestos or fiber exposure was studied. The study tested immunostaining with antibody 4A4 against p63 and antibody D5/16B4 against CK5/6. A positive reaction required at least moderate staining intensity in more than 10% of tumor cells.
• Main results:
  • p63 was positive in 59 of 73 squamous cell carcinomas (81%).
  • p63 was positive in 20 of 141 non–squamous cell carcinomas (14%). This gave a specificity for squamous cell carcinoma of 0.86, calculated against non–squamous cell carcinomas excluding urothelial carcinomas.
  • Urothelial carcinoma was the only other carcinoma type in which most cases were p63-positive: 14 of 20 (70%).
  • None of the 14 malignant mesotheliomas was positive for p63.
  • CK5/6 had a sensitivity of 0.84 for squamous cell carcinomas. It was positive in 30 of 141 non–squamous cell carcinomas (21.3%), giving a specificity of 0.79.
  • Breast carcinomas were CK5/6-positive in 17 of 28 cases (61%) but p63-positive in only 3 of 28 (11%).
  • All 14 malignant mesotheliomas and 7 of 20 urothelial carcinomas (35%) were positive for CK5/6.
  • Both markers were positive in more than 10% of tumor cells in 56 of 73 squamous cell carcinomas (sensitivity 0.77) and in 5 of 141 non–squamous cell carcinomas (specificity 0.96). Specificity was calculated against non–squamous cell carcinomas, excluding urothelial carcinomas.
  • Both markers were positive in more than 50% of tumor cells in 48 of 73 squamous cell carcinomas (sensitivity 0.66) and in 1 of 141 non–squamous cell carcinomas (specificity 0.99).
  • Sensitivity and specificity were calculated for squamous cell carcinomas versus non–squamous cell carcinomas, excluding urothelial carcinomas.
• The authors' conclusion: The authors concluded that p63 and CK5/6 used together could identify about 70% to 80% of poorly differentiated squamous cell carcinomas with a specificity above 0.95. They also concluded that p63 can be used to distinguish pleural or peritoneal metastases of nonkeratinizing squamous cell carcinomas from primary solid malignant mesotheliomas.
• Limitations the authors state:
  • The authors did not study rarer carcinomas that also express p63, such as carcinomas with myoepithelial differentiation or sebaceous carcinomas.
  • Because many urothelial carcinomas are also positive for p63 and CK5/6, the authors stated that other markers are needed to tell urothelial and squamous cell carcinomas apart.
  • Intercellular bridges, the feature that defines squamous cell carcinoma, are hard to verify in poorly differentiated metastases. The authors therefore grouped grade 3 squamous cell carcinomas and grade 4 carcinomas of the same primary sites together.

Topics

Medical terms in this study, explained in our Lexicon: Cytokeratin 5/6, Differential Diagnosis, Carcinoma, Squamous Cell Carcinoma, Mesothelioma.

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