The major protein isoform of p63 expressed in SCC is ΔNp63α, an N-terminally truncated form which functions as a key SCC cell survival factor by mechanisms that are unclear.
Remarkably, a similar spectrum of phenotypic alterations is observed in human syndromes resulting from Tp63 gene mutations. p63 is an important hub in the transcriptional and signaling networks of epithelial cells; thus, it is not surprising that dysregulation of this transcription factor is associated with squamous cell carcinoma.
These data identify a new transcriptional programme mediated by p63 regulation of the Basonuclin 1 transcription factor in squamous cell carcinomas and provide a novel link of p63 with the regulation of ribosomal biogenesis in epithelial cancer.
Spatial proximity between bronchus and ALK-rearranged tumors and frequent solid histologic subtype with p63 expression may cause diagnostic difficulties to differentiate squamous cell carcinoma in the small biopsy, whereas p40 was rarely expressed in ALK-rearranged adenocarcinoma.
The identification of the SCC-associated interaction between SOX2 and p63 will enable deeper characterization the downstream targets of this interaction in SCC and normal squamous epithelial physiology.
In the SCCA versus SCC differential diagnosis, p40 and K903 are each marginally more sensitive (92%) than p63 (88%), whereas CK5/6 boasts the greatest specificity (98%). p63's poor specificity (66%) can be improved to 94%, if an H-score ≥150 is used as the cutoff for a positive result.
To improve segregation between ADC and SqCC in small samples, the classification of lung cancer was updated in 2011, adding immunohistochemistry (IHC) for p63 and TTF-1 to the diagnostic algorithm.
Finally, analysis of samples from patients with squamous cell carcinoma (SCC), basal cell carcinoma and precursors to invasive SCC demonstrated a significant correlation between p63 and VDR levels when compared with healthy normal skin control samples.
The transcription factor p63 belongs to the p53/p63/p73 family and plays key functional roles during normal epithelial development and differentiation and in pathological states such as squamous cell carcinomas.
Squamous cell carcinomas were confirmed using both histological examination by pathologists and immunohistochemistry analysis with positive staining of P63 and CK5/6 combined with negative CK7 and TTF-1 staining.
These results demonstrate that some SCC cell lines are deficient in global nucleotide excision repair and support a role for p63 as a regulator of nucleotide excision repair in SCCs.
Ber EP4 and MOC 31 immunostains were positive in most cases when performed, and the most specific immunostains for SCC were p63 and p40.Negative mucin stains were helpful.