Utility of five commonly used immunohistochemical markers TTF‐1, Napsin A, CK7, CK5/6 and P63 in primary and metastatic adenocarcinoma and squamous cell carcinoma of the lung: a retrospective study of 246 fine needle aspiration cases

Abstract

Background Fine needle aspiration (FNA) biopsy plays a critical role in the diagnosis and staging of lung primary and metastatic lung carcinoma. Accurate subclassification of adenocarcinoma (ADC) and/or squamous cell carcinoma (SqCC) is crucial for the targeted therapy. However, the distinction between ADC and SqCC may be difficult in small FNA specimens. Here, we have retrospectively evaluated the utility of TTF-1, Napsin A, CK7, P63 and CK5/6 immunohistochemical (IHC) markers in the distinguishing and subclassification of ADC and SqCC. Methods A total of 246 FNA cases were identified by a computer search over a two-year period, including 102 primary NSCLC and 144 primary NSCLC which had metastasized to other sites. The immunostaining patterns of TTF-1, Napsin A, CK7, P63 and CK5/6 were correlated with the histological diagnosis of the tumor. Results In 72 primary ADCs, TTF-1, Napsin A and CK7 showed a sensitivity and specificity of 84.5%/96.4%, 92.0%/100%, and 93.8%/50.0%. In 30 primary SqCCs, CK5/6 and P63 showed a sensitivity and specificity of 100%/77.8% and 91.7%/78.3%. In 131 metastatic ADCs, Napsin A showed the highest specificity (100%), versus TTF-1 (87.5%) and CK7 (25%) but decreased sensitivity (67.8% versus 86.9% and 100%); whereas in 13 metastatic SqCCs, CK5/6 and P63 showed a sensitivity/specificity of 100%/84.6% and 100%/68.4%. Bootstrap analysis showed that the combination of TTF-1/CK7, TTF-1/Napsin A and TTF-1/CK7/Napsin A had a sensitivity/specificity of 0.960/0.732, 0.858/0.934, 0.972/0.733 for primary lung ADCs and 0.992/0.642, 0.878/0.881, 0.993/0.618 for metastatic lung ADCs. Conclusions Our study demonstrated that IHC markers had variable sensitivity and specificity in the subclassification of primary and metastatic ADC and SqCC. Based on morphological findings, an algorithm with the combination use of markers aided in the subclassification of NSCLCs in difficult cases.

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

“…These biomarkers have different sensitivities and specificities. Our studies and others' studies have demonstrated that these markers have sensitivities and specificities ranging from approximately 70-100% for the identification of ADCs, and from approximately 60-100% for the identification of SqCCs [7,8]. Limitations of these biomarkers include: the requirement of multiple tissue sections for IHC study, which may exhaust tumor tissue, compromising the molecular characterization of the tumor in small biopsy samples; the time-consuming nature of IHC testing, which can result in prolonged turnaround times, significantly affecting the patient's clinical management; the interpretation of the IHC results may be influenced by nonspecific staining of non-neoplastic cells, such as, pulmonary alveolar macrophages and bronchial basal cells; and different clones of the same antibody may have different effects on the IHC staining pattern.…”

“…In daily clinical practice, the most commonly used IHC biomarkers are TTF-1, napsin A, mucin, CK5/6, P63 and P40 for the classification of NSLCLs [7,8].…”

Roles of CEACAM1 in cell communication and signaling of lung cancer and other diseases

“…CEACAM1 is a necessary and limiting factor in the mechanism of the angiogenesis, since the new generation of capillaries cold be hardly completed with CEACAM1 [22]. Endothelium-derived nitric oxide (NO) as a critical regulator of vascular function was over-produced by the stimulation of VEGF via PI3K/Akt-dependent endothelial NO synthase (eNOS) activation [23]. VEGF failed to mediate eNOS activation and production without the existence of CEACAM1 [24].…”

Subtyping of Non-Small Cell Lung Carcinoma in Fine Needle Aspiration Specimens: A Study of 252 Patients with Surgical Correlations

“…Nonsmall cell lung cancer, with the introduction of new treatment modalities, recognition and differential diagnosis between adenocarcinoma and squamous cell carcinoma is necessary for effective molecular target-specific treatments (2,3). Targets include epidermal growth factor receptors (EGFR), tyrosine kinase inhibitors (TKIs), and echinoderm microtubule associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion protein (4).…”