Abstract
BackgroundA number of biomarkers have the potential of differentiating between primary lung tumours and secondary lung tumours from the gastrointestinal tract, however, a standardised panel for that purpose does not exist yet. We aimed to identify the smallest panel that is most sensitive and specific at differentiating between primary lung tumours and secondary lung tumours from the gastrointestinal tract.MethodsA total of 170 samples were collected, including 140 primary and 30 non-primary lung tumours and staining for CK7, Napsin-A, TTF1, CK20, CDX2, and SATB2 was performed via tissue microarray. The data was then analysed using univariate regression models and a combination of multivariate regression models and Receiver Operating Characteristic (ROC) curves.ResultsUnivariate regression models confirmed the 6 biomarkers’ ability to independently predict the primary outcome (p < 0.001). Multivariate models of 2-biomarker combinations identified 11 combinations with statistically significant odds ratios (ORs) (p < 0.05), of which TTF1/CDX2 had the highest area under the curve (AUC) (0.983, 0.960–1.000 95% CI). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 75.7, 100, 100, and 37.5% respectively. Multivariate models of 3-biomarker combinations identified 4 combinations with statistically significant ORs (p < 0.05), of which CK7/CK20/SATB2 had the highest AUC (0.965, 0.930–1.000 95% CI). The sensitivity, specificity, PPV, and NPV were 85.1, 100, 100, and 41.7% respectively. Multivariate models of 4-biomarker combinations did not identify any combinations with statistically significant ORs (p < 0.05).ConclusionsThe analysis identified the combination of CK7/CK20/SATB2 to be the smallest panel with the highest sensitivity (85.1%) and specificity (100%) for predicting tumour origin with an ROC AUC of 0.965 (p < 0.001; SE: 0.018, 0.930–1.000 95% CI).
Highlights
A number of biomarkers have the potential of differentiating between primary lung tumours and secondary lung tumours from the gastrointestinal tract, a standardised panel for that purpose does not exist yet
Accurate classification falls on the shoulders of the anatomical pathologist and depends on a number of factors including the quality of the biopsy, the experience of the pathologist, and the extent of tumour differentiation
Secondary tumours not originating from the gastrointestinal tract (GIT) were excluded as their biomarker staining pattern is different to that of GIT tumours
Summary
A number of biomarkers have the potential of differentiating between primary lung tumours and secondary lung tumours from the gastrointestinal tract, a standardised panel for that purpose does not exist yet. The 6 main types are epithelial, neuroendocrine, mesenchymal, lymphohistocytic, tumours of ectopic origin, and metastatic tumours, while the most important subtypes include adenocarcinoma and squamous, small, and large-cell carcinomas [3]. Another method of classification looks at the neoplastic cells’ site of origin and classifies tumours as either primary (arising directly from the lungs), or secondary (metastasising to the lung from a distant site). Differentiated tumours on the other hand do not have a clear histopathological pattern and their classification was traditionally highly dependent on the pathologist’s level of expertise This introduced inconsistencies in diagnosis, classification, and patient management. Some biomarkers are preferentially expressed in certain types of tissue but not in others, offering a method of objectively identifying the histological subtype of a tumour even if it exhibits poor differentiation
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