ALK rearrangement in specific subtypes of lung adenocarcinoma: immunophenotypic and morphological features

Abstract

Lung adenocarcinomas are characterized by a variety of genetic and epigenetic changes that lead to activation of specific signaling pathways. This allowed the classification of lung adenocarcinomas according to genetic alterations and the clinical development of novel anticancer agents that affect the activity of specific oncoproteins. In such a context, chromosomal rearrangements that cause constitutive activation of ALK gene define a category of lung adenocarcinomas that is amenable to targeted therapy with ALK inhibitors. Thus, a major issue of current research is to define the morphological and immunophenotypic features of lung ALK-rearranged adenocarcinomas to improve the selection of tumors suitable for molecular genotyping. ALK status was determined, by immunohistochemistry and fluorescence in situ hybridization, in 94 surgically resected lung adenocarcinomas and correlated with histomorphological parameters. Indeed, ALK rearrangement was observed in 10/94 (11%) lung adenocarcinomas and enriched in tumors with a predominant mucinous (46%; p < 0.05) and solid (29%; p < 0.05) pattern. By contrast, it was lacking or sporadically observed in lung adenocarcinomas with predominant acinar, papillary or lepidic pattern. Moreover, the presence of signet-ring cells was predominantly observed in ALK-rearranged tumors (47%; p < 0.05). These data suggest that ALK rearrangement is associated with specific and distinct clinical-pathological characters compared to other genotypes. Thus, the knowledge of these characteristics can improve the diagnostic accuracy and lead to a better understanding of the behavior of ALK-rearranged NSCLC.

Feasibility and Safety of Neoadjuvant Alectinib in Pulmonary Invasive Mucinous Adenocarcinoma with ALK Rearrangement: Case Report and Literature Review

“… 26 Furthermore, morphologically, ALK rearrangement is abundant in adenocarcinoma with signet ring cells. 27 In terms of reality, the ALK-rearranged IMA has acinar and solid growth tumor foci, and is rich in signet ring cells, which was consistent with the findings of our case.…”

Targeted Sequencing Analysis of Predominant Histological Subtypes in Resected Stage I Invasive Lung Adenocarcinoma

“…Micropapillary componentpositive patients with EGFR mutations can benefit from EGFR-TKIs [31,32]; while solid predominant subtype is a negative response predictor for EGFR-TKI [33]. ALK rearrangements were significantly associated with solid predominant subtype and component of signet-ring cells [34][35][36][37][38]. KRAS mutations were more commonly occurred in invasive mucinous adenocarcinoma [21] and solid predominant tumors [22,39].…”

Worse disease-free, tumor-specific, and overall survival in surgically-resected lung adenocarcinoma patients with ALK rearrangement

“…We found that the prevalence was 7.9%, which is consistent with other studies. ALK rearrangement has previously been shown to be more common in light smokers or never-smokers [ 22 – 30 ], females [ 23 – 25 , 28 ], the solid predominant with mucin production adenocarcinoma subtype [ 37 – 39 ], and young patients [ 22 , 24 , 26 , 28 , 30 , 31 ]. However, ALK rearrangement has been reported in males ( P = 0.039) [ 22 ] and some studies have observed no sex difference [ 23 , 26 , 29 – 31 ].…”