p40 and MAdL: excellent new markers for lung carcinomas
Lung cancer is one of the most common cancers worldwide. The many existing subtypes are treated with therapies which differ substantially. In general, physicians discriminate between small-cell lung cancer (SCLC) and non small-cell lung cancer. Subtypes of these are adenocarcinomas, squamous cell carcinomas or different types of large-cell carcinomas. For selecting the optimal therapy it is extremely important to detect and discriminate these subtypes during the diagnosis of the tissue.
Recently, Zytomed Systems launched two new antibodies which help to diagnose the lung cancer subtypes more clearly. Compared with other commonly used antibodies they show higher specificity and/or sensitivity to their target protein. Thus, they are helpful new tools for improving the investigation of lung carcinomas.
Anti-p40 is a promising new antibody that may be a valuable marker in cases where anti-p63 traditionally has been used. In the moment p63 is the most commonly used antibody for detecting lung squamous cell carcinomas. It shows a high sensitivity but often also detects adenocarcinomas; according to Au et al. in up to 30% of all cases.
The p40 protein, an N-terminal truncated form of p63 protein (?Np63), seems to be more strictly associated with squamous cell carcinomas than p63. Recent studies (Bishop et al. and Nonaka) show that p40 staining is equivalent to p63 in sensitivity for squamous cell carcinoma but shows a considerably higher specificity. In the large study of Bishop et al. the sensitivity of p40 for lung squamous cell carcinomas is 100% and the specificity 98% whereas p63 only shows a specificity of 60% for this tumour entity.
Both groups conclude that p40 is superior to p63 when detecting squamous cell carcinomas of the lung, especially when it is important to differentiate them from adenocarcinomas of the lung.
MAdL (Marker for Adenocarcinomas of the Lung) is a new specific marker for lung adenocarcinomas as described by Schultz et al. Its outstanding specificity of >99% and sensitivity of 76.5% for lung adenocarcinomas makes anti-MAdL a very useful tool for sub-differentiation of lung tumours. Compared with TTF-1, which is the most commonly used lung adenocarcinoma marker, MAdL shows a higher specificity. TTF-1 detects lung adenocarcinomas but also some small-cell lung carcinomas, carcinoids and large-cell endocrine tumours whereas MAdL is not expressed in small-cell lung carcinomas and carcinoids. Also Napsin A shows less specificity than MAdL. The expression of MAdL remains constant with increasing malignity of the tumour. This distinguishes MAdL from other markers like Surfactant Protein A and B. Extensive testing has shown that MAdL immunohistochemistry on formalin-fixed tissue works best after proteolytic digestion. We recommend using Pepsin for the pre-treatment.
 Nonaka D. "A study of ?Np63 expression in lung Non-Small Cell Carcinomas" Am J Surg Pathol 36:895-899, 2012
 Bishop JA et al. "p40 (?Np63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma" Mod Pathol 25:405-415, 2012
 Pelosi G et al. "?Np63 (p40) and thyroid transcription factor-1 immunoreactivity on small biopsies or cellblocks for typing non-small cell lung cancer: a novel two-hit, sparing-material approach" J Thorac Oncol 7:281-290, 2012
 Au NH et al. "p63 expression in lung carcinoma: a tissue microarray study of 408 cases" Appl Immunohistochem Mol Morphol 12:240-247, 2004
 Schultz H et al. „Generation and evaluation of a monoclonal antibody, designated MAdL, as a new specific marker for adenocarcinomas of the lung" Brit J Cancer 105:673-681, 2011
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