Which immunohistochemical marker pair is most characteristic of squamous differentiation?

• A. p63/p40
• B. Synaptophysin & chromogranin
• C. TTF-1 & Napsin A
• D. HMB45 & Melanin A

Answer: (A)

Squamous differentiation is best identified by markers that are characteristic of squamous epithelium, particularly in basal and mature squamous cells. p63 is a nuclear transcription factor expressed in the basal layer of stratified squamous epithelium and in squamous cell carcinomas, so it shows strong nuclear staining in these cells. p40, an isoform of p63, is more specific for squamous differentiation and is often used alongside p63 because it helps distinguish squamous lineage from other non-squamous tumors. Together, positivity for p63 and p40 provides strong evidence of squamous differentiation, which is why this pair is the best choice.

Markers like Synaptophysin and chromogranin highlight neuroendocrine features and are not characteristic of squamous cells. TTF-1 and Napsin A are commonly associated with lung adenocarcinoma. HMB45 and Melan-A mark melanocytic lineage.