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Analysis of Histologic Features Suspecting Anaplastic Lymphoma Kinase (ALK)-Expressing Pulmonary Adenocarcinoma

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Background: Since 2007 when anaplastic lymphoma kinase (ALK) rearrangements were discovered in non-small cell lung cancer, the ALK gene has received attention due to ALK-targeted therapy, and a notable treatment advantage has been observed in patients harboring the EML4/ALK translocation. However, using ALK-fluorescence in situ hybridization (FISH) as the standard method has demerits such as high cost, a time-consuming process, dependency on interpretation skill, and tissue preparation. We analyzed the histologic findings which could complement the limitation of ALK-FISH test for pulmonary adenocarcinoma. Methods: Two hundred five cases of ALK-positive and 101 of ALK-negative pulmonary adenocarcinoma from January 2007 to May 2013 were enrolled in this study. The histologic findings and ALK immunohistochemistry results were reviewed and compared with the results of ALK-FISH and EGFR/KRAS mutation status. Results: Acinar, cribriform, and solid growth patterns, extracellular and intracellular mucin production, and presence of signet-ring-cell element, and psammoma body were significantly more often present in ALK-positive cancer. In addition, the presence of goblet cell-like cells and presence of nuclear inclusion and groove resembling papillary thyroid carcinoma were common in the ALK-positive group. Conclusions: The above histologic parameters can be helpful in predicting ALK rearranged pulmonary adenocarcinoma, leading to rapid FISH analysis and timely treatment.

Abstract

Background: Since 2007 when anaplastic lymphoma kinase (ALK) rearrangements were discovered in non-small cell lung cancer, the ALK gene has received attention due to ALK-targeted therapy, and a notable treatment advantage has been observed in patients harboring the EML4/ALK translocation. However, using ALK-fluorescence in situ hybridization (FISH) as the standard method has demerits such as high cost, a time-consuming process, dependency on interpretation skill, and tissue preparation. We analyzed the histologic findings which could complement the limitation of ALK-FISH test for pulmonary adenocarcinoma. Methods: Two hundred five cases of ALK-positive and 101 of ALK-negative pulmonary adenocarcinoma from January 2007 to May 2013 were enrolled in this study. The histologic findings and ALK immunohistochemistry results were reviewed and compared with the results of ALK-FISH and EGFR/KRAS mutation status. Results: Acinar, cribriform, and solid growth patterns, extracellular and intracellular mucin production, and presence of signet-ring-cell element, and psammoma body were significantly more often present in ALK-positive cancer. In addition, the presence of goblet cell-like cells and presence of nuclear inclusion and groove resembling papillary thyroid carcinoma were common in the ALK-positive group. Conclusions: The above histologic parameters can be helpful in predicting ALK rearranged pulmonary adenocarcinoma, leading to rapid FISH analysis and timely treatment.

참고문헌 (11)

  1. Soda M, "Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer", Nature, 448, pp.561~566 (2007)
  2. Sun JM, "Clinical characteristics associated with ALK rearrangements in never-smokers with pulmonary adenocarcinoma", Lung Cancer, 83, pp.259~264 (2014)
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  4. Paik JH, "Screening of anaplastic lymphoma kinase rearrangement by immunohistochemistry in non-small cell lung cancer : correlation with fluorescence in situ hybridization", J Thorac Oncol, 6, pp.466~472 (2011)
  5. Yi ES, "Correlation of IHC and FISH for ALK gene rearrangement in non-small cell lung carcinoma : IHC score algorithm for FISH", J Thorac Oncol, 6, pp.459~465 (2011)
  6. Yoshida A, "Comprehensive histologic analysis of ALK-rearranged lung carcinomas", Am J Surg Pathol, 35, pp.1226~1234 (2011)
  7. Jokoji R, "Combination of morphological feature analysis and immunohistochemistry is useful for screening of EML4-ALK-positive lung adenocarcinoma", J Clin Pathol, 63, pp.1066~1070 (2010)
  8. Inamura K, "EML4-ALK fusion is linked to histological characteristics in a subset of lung cancers", J Thorac Oncol, 3, pp.13~17 (2008)
  9. Inamura K, "EML4-ALK lung cancers are characterized by rare other mutations, a TTF-1 cell lineage, an acinar histology, and young onset", Mod Pathol, 22, pp.508~515 (2009)
  10. Rodig SJ, "Unique clinicopathologic features characterize ALK-rearranged lung adenocarcinoma in the western population", Clin Cancer Res, 15, pp.5216~5223 (2009)
  11. Kim H, "A comprehensive comparative analysis of the histomorphological features of ALK-rearranged lung adenocarcinoma based on driver oncogene mutations: frequent expression of epithelial-mesenchymal transition markers than other genotype", PLoS One, 8, pp.e76999~ (2013)

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