Overview of clinicopathologic features of ALK-rearranged lung adenocarcinoma and current diagnostic testing for ALK rearrangement

Abstract

Patients with non-small cell lung cancer (NSCLC) who harbor anaplastic lymphoma kinase (ALK) gene rearrangements can derive significant clinical benefit from ALK tyrosine kinase inhibitor. Accurate patient identification is absolutely crucial for successful using ALK inhibitor treatment. However, lung cancer patients with ALK gene rearrangement after ALK inhibitor therapy eventually develop acquired resistance to treatment. In this review, the authors summarize the clinicopathologic features of ALK-rearranged NSCLC and the pros and cons of current diagnostic testing. In addition, we discuss the current diagnostic flow of ALK testing and consideration of rebiopsy sample during disease progression in patients treated by ALK inhibitors.

Keywords: Anaplastic lymphoma kinase (ALK) gene rearrangement; fluorescent in situ hybridization (FISH); histology; immunohistochemistry (IHC); non-small cell lung cancer (NSCLC).

Figure 1

Relationship of ALK-rearranged tumors with the bronchiole. (A) Tumor cells invaded the adjacent bronchiolar epithelium (magnification, 10×); (B) at higher magnification, dysplastic epithelial lesions that resembled adjacent tumor cells continued the non-neoplastic bronchial epithelium (magnification, 20×). ALK, anaplastic lymphoma kinase.

Figure 2

(A) Dual nuclear expression of TTF-1 (magnification, 40×) and (B) p63 in ALK-rearranged tumors (magnification, 40×). ALK, anaplastic lymphoma kinase.

Figure 3

(A) ALK protein expression on immunohistochemistry using 5A4 antibody (magnification, 40×) and (B) D5F3 antibody (magnification, 40×). ALK, anaplastic lymphoma kinase.