The utility of a novel triple marker (combination of TTF1, napsin A, and p40) in the subclassification of non–small cell lung cancer

Abstract

Summary In lung cancer, targeted therapies depend on accurate histological subclassification of the tumor. The majority of lung cancers can be subclassified based on hematoxylin and eosin staining; however, classification may be difficult in small biopsies. In this study, we investigated the utility of a newly developed triple marker (combination of TTF1/Napsin A/p40) and compared the sensitivity and specificity of this novel marker with individual markers in the subclassification of non–small cell lung carcinomas. Lung cancer tissue microarrays were constructed using surgical resection material from the Johns Hopkins Hospital. They included 77 adenocarcinomas (ADCs), 77 squamous cell carcinomas (SqCCs), and 46 cases of metastatic lung ADCs. Immunostaining patterns of all markers were scored semi-quantitatively and compared. In ADCs, the sensitivity and specificity of the triple marker were 93.5% and 77.5%, respectively. The sensitivity and specificity of TTF1 and Napsin A were 85.7% and 75.0%, and 89.6% and 90.0%. In SqCCs, the sensitivity and specificity of the triple marker were 88.3% and 92.5%, while the p40, p63 and CK5/6 showed 80.5% and 90.0%; 93.5% and 80.0%; and 89.6% and 80.0%. In addition, the sensitivity and specificity of the triple marker in metastatic ADCs showed 71.7% and 73.5%, respectively. Our triple marker (combination of TTF1/Napsin A/p40) showed a similar sensitivity and specificity for the subclassification of NSCLC when compared to individual markers. Our study not only demonstrates a useful combination of immunomarkers but also optimally conserves tissue for molecular marker testing.

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

“…It is also used for the identification of primary lung ADC and metastatic lung ADC outside the thyroid [11,12]. The sensitivity and specificity of TTF-1 in lung ADC diagnosis are reported to be 60-89 and 75-98 %, respectively [6,13,14]. In this study, the sensitivity and specificity of TTF-1 in the identification of lung ADC among lung SQCC were 87.0 and 90.4 %, respectively.…”

“…IHC staining has shown that Napsin A is expressed in the cytoplasm. The sensitivity and specificity of Napsin A for detecting lung ADC are reported to be 83-90 and 90-98 %, respectively [6,14,18], which are higher than those for TTF-1. In this study, the sensitivity and specificity of Napsin A for identifying lung ADC among lung SQCC were 72.2 and 90.4 %, respectively.…”

Biomarkers in the Accurate Subclassification of Non-Small-Cell Lung Carcinoma for Targeted Therapy: Issues and Prospects

“…In our study, the triple marker demonstrates a similar sensitivity and specificity as the individual IHC biomarkers. It has demonstrated a sensitivity of 86.0% and a specificity of 100% in lung ADCs, and a sensitivity of 100% and a specificity of 97.1% in lung SqCCs [9,10]. Our practice also indicates that the utility of a combined IHC approach is a cost-effective method of subclassifying lung cancer in daily practice.…”

The role of Napsin-A and Desmocollin-3 in classifying poorly differentiating non-small cell lung carcinoma

“…In the literature, the sensitivity of Napsin-A for lung adenocarcinoma ranged from 58% to 90%, and specificity from 90.7% to 100% [7,[13][14][15][16][17][18][19].…”