TTF-1 and Napsin a Double Staining in Diagnosing Lung Adenocarcinoma

Abstract

Pulmonary cancer is the most commonly diagnosed cancer worldwide, and is the leading cause of cancer mortality in men [1]. Lung cancer is divided into small cell cancer and Non-Small Cell Cancer (NSCLC). NSCLC accounts for 80% of all lung cancers and is comprised of Adenocarcinoma (ADC), Squamous Cell Carcinoma (SqCCA) and large cell carcinoma [2]. In addition, 60% of NSCLCs present with locally advanced disease at the time of initial diagnosis [3]. Traditionally, the pathologic lung cancer differential diagnosis was between small cell carcinoma and NSCLC, as sub-typing NSCLC had not been shown to predict differences in patient outcomes. Recent advances in molecular biology have led to an increase in target-specific chemotherapeutic therapies that require the sub-categorization of NSCLCs. The International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society has outlined a new classification of lung ADCs based on a multidisciplinary approach. They have outlined the importance of further classifying NSCLCs as either ADCs or SqCCAs, since ADCs should be tested for Epidermal Growth Factor Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK) fusion gene mutations, as targeted chemotherapeutic agents can be used with greater efficacy [4]. Lung ADCs are often associated with EGFR mutations, and can be effectively treated with tyrosine kinase inhibitors such as gefitinib [5,6]. In addition, ADC have been shown to have improved outcomes when compared to SqCCAs when treated with pemetrexed therapy, which inhibits specific enzymes in purine and pyrimidine synthesis. Finally, the distinction between ADC and SqCCA can avoid potentially hazardous outcomes, as life-threatening hemorrhages have been rarely reported when patients with SqCCAs are treated with bevacizumab, a vascular endothelial growth factor inhibitor [7]. If the classification of NSCLCs cannot be achieved with cytologic/histologic criteria alone, Immunohistochemistry (IHC) staining should be employed. Thyroid Transcription Factor 1 (TTF-1) and Napsin A are both stains that have been proven to stain a majority of lung ADCs. TTF-1 is a nuclear stain that has been reported in 87% lung ADCs and 2% of SqCCAs [8]. Napsin A is a cytoplasmic stain that is relatively specific for ADC of the lung and reportedly stains 80% of cases [9]. A combined TTF-1 and Napsin A double stain has also been shown to be useful in the diagnosis of ADC in cell blocks from fine needle aspirates (FNAs) [10].