p40: A p63 Isoform Useful for Lung Cancer Diagnosis – A Review of the Physiological and Pathological Role of p63

Abstract

At present, p63, TTF-1, and Napsin-A are the main immunochemical markers used to distinguish squamous cell carcinoma (SCC) from lung adenocarcinoma (ADC). However, studies using antibodies against p63 have demonstrated false-positive results with positivity in some ADC. In contrast, the expression of one of the p63 isoforms (ΔNp63), detected by the antibody p40, is highly specific for SCC. Since most cases of lung cancer are diagnosed in small specimens (cytology/biopsies) and saving material for molecular analysis is mandatory, we recommended the use of p40 (in adjunct with TTF-1 and/or Napsin-A) as the best approach to discriminate SCC and lung ADC. In this paper, we review the physiological and pathological role of p63 isoforms as well as their use as diagnostic markers in lung SCC.

Utilization of p40 (ΔNp63) with p63 and Cytokeratin 5/6 Immunohistochemistry in Non-Small Cell Lung Carcinoma Fine-Needle Aspiration Biopsy

“…These have centered on subtyping AdCA and SCCA, with different individual and combinations/panels of antibodies advocated. More recently, p40 (ΔNp63) has been described as being specific for SCCA [5]. To our knowledge, the concomitant use of p40 and p63/CK5/6 in FNA biopsy material has not been previously described.…”

“…Nobre et al [5], in a review article, discuss the physiologic role of p63 isoforms and their use as diagnostic markers in lung SCCA, and they recommend the use of p40 in discriminating SCCA and AdCA. p63, the more commonly used antibody, has shown good sensitivity for SCCA [2,8,9,10,11,12], yet it has been shown to have reactivity in non-squamous cell carcinoma, including large cell lymphoma and lung AdCA [9,13,14,15,16].…”

p40 is a more specific marker than p63 for cutaneous poorly differentiated squamous cell carcinoma

“…22 In normal epidermis, both p63 and p40 stain the basal layer, and nuclear staining for p63 can also be seen in suprabasal keratinocytes. 23 One of the common uses of p63 in neoplastic tissue takes advantage of its sensitivity for SCC in several organs, especially in the lung, esophagus and head and neck tumors. 7,13,22,24,25 Importantly, in these organs, p40 has shown superior specificity while maintaining a comparable level of sensitivity.…”

The expression of TTF-1 and Napsin A in early-stage lung adenocarcinoma correlates with the results of surgical treatment

“…Immunohistochemical staining is an important technique in the accurate classification of lung cancer. Commonly used ADCspecific identification markers are thyroid transcription factor 1 (TTF-1), Napsin A, and CK7, which have been used as diagnostic indicators as suggested in several reliable studies [1,5,6]. If these good diagnostic indicators can also be used to determine prognosis, then the clinical significance of these markers will be broadened and they will become even more important.…”