Discrepancies Between Morphological and Immunohistochemical Classifications Are Associated With Prognoses and Subtypes of Lung Cancer

Background/Aim: Immunohistochemical (IHC) staining has been routinely used to distinguish adenocarcinoma (ADC) and squamous cell carcinoma (SCC) of the lungs; however, it is challenging to obtain an accurate diagnosis, especially for cases with discrepancies between IHC and hematoxylin and eosin (H&E) staining results. This study aimed to clarify the clinicopathological characteristics of these discrepant cases. Patients and Methods: Tissue microarray specimens from 321 patients with ADC and SCC were used for H&E and IHC staining of thyroid transcription factor 1 (TTF1), Napsin A, cytokeratin 5/6 (CK5/6), p40, and p63. The pathological diagnosis was made based on (1) H&E, (2) IHC, and (3) both H&E and IHC results. Discrepant cases were defined as those with different diagnoses based on the H&E and IHC results. Results: A total of 32 (10%) discrepant cases were identified. ADC (3.9%) showed fewer discrepant cases than SCC (51%). Discrepant cases of ADC had a significantly higher proportion of poorly differentiated tumors and subtypes of solid and invasive mucinous ADC, and they also had shorter overall and disease-free survival than concordant cases. Solid and invasive mucinous ADC cases showed low positivity for TTF-1 (84% and 40%, respectively) and Napsin A (88% and 80%, respectively), and invasive mucinous ADC cases showed high positivity for CK5/6 (80%). The sensitivity and specificity of TTF-1+Napsin A for ADC were 91% and 83%, respectively, whereas those of CK5/6+p40 for SCC cases were 90% and 96%, respectively. Conclusion: Discrepant cases of ADC are associated with solid and invasive mucinous subtypes and shorter survival.