The diagnostic utility of p40 immunohistochemistry in pulmonary squamous cell carcinoma

Abstract

Accurate histological diagnosis of the two main sub-types of non-small cell lung carcinoma (NSCLC), namely squamous cell carcinoma (SCC) and adenocarcinoma (ADC) is fundamental due to the different therapeutic strategies available. One of the current immunostains used for the diagnosis of SCC is protein 63 (p63), which is highly sensitive. However, p63 has low specificity since it shows positivity in some lung ADCs and in several other tumours which can present as lung metastasis. The gene p63 encodes two opposing isomers, that vary in the structure of the N-terminal domain: transactive protein 63 (TAp63), acting as a tumour suppressor and deltaNp63 (∆Np63), acting as an oncogene. In lung SCC, the ∆Np63 isoform is predominantly expressed. Recently, protein 40 (p40) was proposed as a highly sensitive and specific marker for lung SCC as it only detects the ∆Np63 isoform, while p63 antibody detects both isomers. One hundred thirty retrospective lung tumours consisting of resection specimens and biopsies of SCC, ADC and metastatic lung tumours from January 2008 to July 2018 were retrieved. An optimised protocol for the novel marker p40 was determined. All cases were stained with p63 and p40 and assessed using the H-score. Two cases which originally were classified as SCC were reclassified as ADC due to negative p40 staining, and another case was excluded from the study as it could not be determined whether the tumour was primary or metastatic. All the 47 lung SCCs expressed p63 and p40. In ADC, p63 was expressed in 31 cases (60%) while p40 was expressed in 7 cases (13%). The sensitivity of both p63 and p40 was 100% for lung SCC. A specificity of 40.4% was obtained for p63 while the specificity of p40 was 86.5%. At a cut-off of equal to or more than 5% tumour positivity, the specificity of p63 was 46.2% while of p40 was 88.5%. The immunomarker p40 is an excellent pulmonary squamous marker to distinguish between lung SCC and ADC and should replace p63 in the routine diagnosis of NSCLC.