Clinicopathological Profile of Anaplastic Lymphoma Kinase-positive Nonsmall Cell Lung Cancer: An Indian Perspective

Abstract

Background: A novel fusion gene of echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) has been identified in a subset of non-small-cell lung cancers (NSCLCs). Patients with the ALK-EML4 fusion gene demonstrate unique clinicopathological and physiological characteristics. Here we present an analysis of clinicopathological profile of patients of metastatic adenocarcinoma harboring the ALK-EML4 fusion gene. Methods: A retrospective analysis of advanced ALK positive NSCLC, who presented at this tertiary care hospital of armed forces from September 2014 to December 2016 was conducted. The primary goal was to evaluate demographic and clinicopathological profile of ALK positive advanced NSCLC. Detection of ALK fusion was done by IHC on formalin fixed paraffin embedded cell blocks. Results: Out of 270 patients of NSCLC, 15 (7.4%) tested positive for ALK-EML4 fusion. Rate of positivity was higher in females (13.7%) than in males (5%). The correlation of the ALK-EML4 fusion gene and clinicopathological characteristics of NSCLC patients demonstrated a significant difference in smoking status, histological types, stage, and metastatic pattern. Conclusion: Our analysis indicated that ALK-EML4 positive NSCLC comprised a unique subgroup of adenocarcinomas with distinct clinicopathological and radiological characteristics. Incidence of ALK positivity was found to be higher in females and never smokers. These patients have distinct pathological and radiological characteristics.

Keywords

Adenocarcinoma - anaplastic lymphoma kinase-echinoderm microtubule-associated protein-like 4 - fluorescent in situ hybridization - immunohistochemistry - metastasis - nonsmall cell lung cancer

Publikationsverlauf

Artikel online veröffentlicht:
23. Juni 2021

• References

• 1 Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S. et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007; 448: 561-6
• 2 Bunning K, Smith C, Kennedy P, Greenham C. Examination of the communication interface between students with severe to profound and multiple intellectual disability and educational staff during structured teaching sessions. J Intellect Disabil Res 2013; 57: 39-52
• 3 Horn L, Pao W. EML4-ALK: Honing in on a new target in non-small-cell lung cancer. J Clin Oncol 2009; 27: 4232-5
• 4 Takahashi T, Sonobe M, Kobayashi M, Yoshizawa A, Menju T, Nakayama E. et al. Clinicopathologic features of non-small-cell lung cancer with EML4-ALK fusion gene. Ann Surg Oncol 2010; 17: 889-97
• 5 Gainor JF, Varghese AM, Ou SH, Kabraji S, Awad MM, Katayama R. et al. ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS: An analysis of 1,683 patients with non-small cell lung cancer. Clin Cancer Res 2013; 19: 4273-81
• 6 Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. et al. Global cancer statistics. CA Cancer J Clin 2011; 61: 69-90
• 7 Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C. et al. Cancer statistics, 2006. CA Cancer J Clin 2006; 56: 106-30
• 8 Ettinger DS, Bepler G, Bueno R, Chang A, Chang JY, Chirieac LR. et al. Non-small cell lung cancer clinical practice guidelines in oncology. J Natl Compr Canc Netw 2006; 4: 548-82
• 9 Miller VA, Kris MG, Shah N, Patel J, Azzoli C, Gomez J. et al. Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small-cell lung cancer. J Clin Oncol 2004; 22: 1103-9
• 10 Tiseo M, Gelsomino F, Boggiani D, Bortesi B, Bartolotti M, Bozzetti C. et al. EGFR and EML4-ALK gene mutations in NSCLC: A case report of erlotinib-resistant patient with both concomitant mutations. Lung Cancer 2011; 71: 241-3
• 11 Takeuchi K, Choi YL, Soda M, Inamura K, Togashi Y, Hatano S. et al. Multiplex reverse transcription-PCR screening for EML4-ALK fusion transcripts. Clin Cancer Res 2018; 14: 6618-24
• 12 Shaw AT, Yeap BY, Mino-Kenudson M, Digumarthy SR, Costa DB, Heist RS. et al. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol 2009; 27: 4247-53
• 13 Shaw AT, Solomon B. Targeting anaplastic lymphoma kinase in lung cancer. Clin Cancer Res 2011; 17: 2081-6
• 14 Corner J, Hopkinson J, Fitzsimmons D, Barclay S, Muers M. Is late diagnosis of lung cancer inevitable? Interview study of patients' recollections of symptoms before diagnosis. Thorax 2005; 60: 314-9
• 15 Rodig SJ, Mino-Kenudson M, Dacic S, Yeap BY, Shaw A, Barletta JA. et al. Unique clinicopathologic features characterize ALK-rearranged lung adenocarcinoma in the Western population. Clin Cancer Res 2009; 15: 5216-23
• 16 Yoshida A, Tsuta K, Watanabe S, Sekine I, Fukayama M, Tsuda H. et al. Frequent ALK rearrangement and TTF-1/p63 co-expression in lung adenocarcinoma with signet-ring cell component. Lung Cancer 2011; 72: 309-15
• 17 Wong DW, Leung EL, So KK, Tam IY, Sihoe AD, Cheng LC. et al. The EML4-ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRAS. Cancer 2009; 115: 1723-33
• 18 Yang P, Kulig K, Boland JM, Erickson-Johnson MR, Oliveira AM, Wampfler J. et al. Worse disease-free survival in never-smokers with ALK+ lung adenocarcinoma. J Thorac Oncol 2012; 7: 90-7