ALK-rearranged pulmonary adenocarcinoma in Thai Patients: From diagnosis to treatment efficacy

Abstract

BackgroundAnaplastic lymphoma kinase (ALK) gene rearrangement is detected in 3 % to 13 % of non-small cell lung carcinoma patients, and these patients benefit from ALK inhibitors. The aim of this study was to determine the prevalence, the clinical and histological characteristics and the treatment outcomes of ALK-rearranged lung adenocarcinoma using immunohistochemistry (IHC) IHC, reverse transcription polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH) methodologies.MethodsA total of 268 pulmonary adenocarcinoma patients were screened for ALK expression by ALK IHC, which was confirmed by FISH and/or RT-PCR for ALK gene rearrangement. The treatment outcomes of ALK-rearranged patients were retrospectively reviewed.ResultsALK gene rearrangement was identified in 26 cases (9.7 %) with no EGFR co-mutation, and it showed significant associations with younger age, female sex and non-smoker status (p < 0.05). A cribriform growth pattern was identified as the dominant histologic feature, and a solid signet ring cell component was focally present in a minority of the cases. Among 12 ALK-rearranged patients with conventional treatment, seven cases in the early stage of disease were cured and alive, and five patients in the late stage of the disease progressed and died, with a median overall survival (OS) at 14 months. Of the 14 patients receiving crizotinib, all of them had clinical benefit from crizotinib treatment, with one patient having a complete response (CR), 12 patients having a partial response (PR) and one patient having stable disease (SD). On the cutoff date, six of 14 patients were continuing crizotinib treatment with a median time of response of 7.5 (3–13) months, while eight patients had disease progression, and five of them died with a median OS at 8 months.ConclusionALK gene rearrangement tended to occur in younger, non-smoking, female patients. ALK IHC is a reliable screening method to detect ALK gene rearrangement. Crizotinib therapy provided treatment benefit in ALK-rearranged adenocarcinoma patients especially in advanced stages of the disease.

Detection of anaplastic lymphoma kinase gene re-arrangement in non-small cell lung carcinoma in the indian population: comparison of techniques and immunohistochemistry clones

“…In this Comprehensive histological analysis in cases with ALK mutation confirmed that these tumours show histologic features distinct from the wild type cancers. Most of these tumours harbour a mixed morphological pattern (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28).…”

Lung adenocarcinoma: from molecular basis to genome-guided therapy and immunotherapy

“…This fusion is created by an inversion of the short arm of chromosome 2 that binds exons 1-13 of EML4 (encoding echinoderm microtubule associated protein like 4) to exons 20-29 of ALK, resulting in the synthesis of a chimerical protein with constitutive ALK activity (86)(87)(88). Patients with ALK-rearranged ADC are usually young, never-smokers and women, showing moderately or poorly differentiated peripheral tumors (89,90). In general, ALK alterations are mutually exclusive with KRAS-EGFR mutations, having prognosis implications due to the impact of guidedtherapies (91).…”

The Prevalence of the EML4-ALK Fusion Gene in Cytology Specimens from Patients with Lung Adenocarcinoma

“…Furthermore, with high sensitivity and specificity and rapid turnaround time and ease of analysis, qRT-PCR can detect as few as 1% of ALK-driven NSCLC cells [ 27 ]. Previous studies have shown that qRT-PCR is an effective method for detecting ALK rearrangement using cytology samples from patients with primary lung cancer [ 16 , 28 – 30 ]. The concordance level between different methods ranges from 99 to 100% in these studies.…”