Heterogeneity of anaplastic lymphoma kinase gene rearrangement in non-small-cell lung carcinomas: A comparative study between small biopsy and excision samples

Hideyuki Abe, Akihiko Kawahara, Koichi Azuma, Tomoki Taira, Yorihiko Takase, Chihiro Fukumitsu, Kazuya Murata, Tomohiko Yamaguchi, Jun Akiba, Hidenobu Ishii, Isamu Okamoto, Tomoaki Hoshino, Shinzou Takamori, Masayoshi Kage

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Abstract

Introduction: The standard diagnostic method for echinoderm microtubule-associated protein-like 4-anaplastic lymphoma receptor tyrosine kinase translocation is fluorescence in situ hybridization (FISH). Recently, immunohistochemistry (IHC) has been reported as a potential method in screening for anaplastic lymphoma kinase (ALK)-positive non-small-cell lung carcinomas (NSCLC), whereas several authors have reported a discordance between FISH and IHC results. We investigated the heterogeneity of ALK gene rearrangement in excision specimens by FISH and also examined whether the FISH score of ALK gene rearrangement corresponded in excision and biopsy samples from the same patient. Methods: Twenty ALK IHC-positive patients including six patients treated with crizotinib therapy were evaluated for the presence of ALK FISH. For evaluation of heterogeneity of ALK gene rearrangement in excision specimens, we defined six to 10 observation areas in each case, and the number of ALK FISH positive observation areas (≥15% rearrangement detected) was investigated. ALK FISH score in small biopsy samples was classified as positive (≥15% rearrangement detected), equivocal (5-14% rearrangement detected), or negative (<4% rearrangement detected). Results: Of a total of 64 tumor observation areas from nine excision specimens, 50 areas were positive for ALK gene rearrangement (81.8%). In the comparison of excision and small biopsy samples, all excision specimens were ALK FISH-positive (100%; 6 of 6), whereas only three of the small biopsy samples in these patients were positive (50%; 3 of 6), two were equivocal (33%; 2 of 6), and one was negative (17%; 1 of 6). The two equivocal patients received crizotinib and showed a response. Conclusion: ALK gene rearrangement heterogeneity was observed in NSCLC specimens by FISH. Our findings suggested that IHC-positive/FISH-equivocal cases should not be considered true "false-negatives" when a small biopsy sample was used for ALK analysis.

Original languageEnglish
Pages (from-to)800-805
Number of pages6
JournalJournal of Thoracic Oncology
Volume10
Issue number5
DOIs
Publication statusPublished - May 30 2015

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Gene Rearrangement
Non-Small Cell Lung Carcinoma
Fluorescence In Situ Hybridization
Biopsy
Immunohistochemistry
Observation
anaplastic lymphoma kinase

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Heterogeneity of anaplastic lymphoma kinase gene rearrangement in non-small-cell lung carcinomas : A comparative study between small biopsy and excision samples. / Abe, Hideyuki; Kawahara, Akihiko; Azuma, Koichi; Taira, Tomoki; Takase, Yorihiko; Fukumitsu, Chihiro; Murata, Kazuya; Yamaguchi, Tomohiko; Akiba, Jun; Ishii, Hidenobu; Okamoto, Isamu; Hoshino, Tomoaki; Takamori, Shinzou; Kage, Masayoshi.

In: Journal of Thoracic Oncology, Vol. 10, No. 5, 30.05.2015, p. 800-805.

Research output: Contribution to journalArticle

Abe, H, Kawahara, A, Azuma, K, Taira, T, Takase, Y, Fukumitsu, C, Murata, K, Yamaguchi, T, Akiba, J, Ishii, H, Okamoto, I, Hoshino, T, Takamori, S & Kage, M 2015, 'Heterogeneity of anaplastic lymphoma kinase gene rearrangement in non-small-cell lung carcinomas: A comparative study between small biopsy and excision samples', Journal of Thoracic Oncology, vol. 10, no. 5, pp. 800-805. https://doi.org/10.1097/JTO.0000000000000507
Abe, Hideyuki ; Kawahara, Akihiko ; Azuma, Koichi ; Taira, Tomoki ; Takase, Yorihiko ; Fukumitsu, Chihiro ; Murata, Kazuya ; Yamaguchi, Tomohiko ; Akiba, Jun ; Ishii, Hidenobu ; Okamoto, Isamu ; Hoshino, Tomoaki ; Takamori, Shinzou ; Kage, Masayoshi. / Heterogeneity of anaplastic lymphoma kinase gene rearrangement in non-small-cell lung carcinomas : A comparative study between small biopsy and excision samples. In: Journal of Thoracic Oncology. 2015 ; Vol. 10, No. 5. pp. 800-805.
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title = "Heterogeneity of anaplastic lymphoma kinase gene rearrangement in non-small-cell lung carcinomas: A comparative study between small biopsy and excision samples",
abstract = "Introduction: The standard diagnostic method for echinoderm microtubule-associated protein-like 4-anaplastic lymphoma receptor tyrosine kinase translocation is fluorescence in situ hybridization (FISH). Recently, immunohistochemistry (IHC) has been reported as a potential method in screening for anaplastic lymphoma kinase (ALK)-positive non-small-cell lung carcinomas (NSCLC), whereas several authors have reported a discordance between FISH and IHC results. We investigated the heterogeneity of ALK gene rearrangement in excision specimens by FISH and also examined whether the FISH score of ALK gene rearrangement corresponded in excision and biopsy samples from the same patient. Methods: Twenty ALK IHC-positive patients including six patients treated with crizotinib therapy were evaluated for the presence of ALK FISH. For evaluation of heterogeneity of ALK gene rearrangement in excision specimens, we defined six to 10 observation areas in each case, and the number of ALK FISH positive observation areas (≥15{\%} rearrangement detected) was investigated. ALK FISH score in small biopsy samples was classified as positive (≥15{\%} rearrangement detected), equivocal (5-14{\%} rearrangement detected), or negative (<4{\%} rearrangement detected). Results: Of a total of 64 tumor observation areas from nine excision specimens, 50 areas were positive for ALK gene rearrangement (81.8{\%}). In the comparison of excision and small biopsy samples, all excision specimens were ALK FISH-positive (100{\%}; 6 of 6), whereas only three of the small biopsy samples in these patients were positive (50{\%}; 3 of 6), two were equivocal (33{\%}; 2 of 6), and one was negative (17{\%}; 1 of 6). The two equivocal patients received crizotinib and showed a response. Conclusion: ALK gene rearrangement heterogeneity was observed in NSCLC specimens by FISH. Our findings suggested that IHC-positive/FISH-equivocal cases should not be considered true {"}false-negatives{"} when a small biopsy sample was used for ALK analysis.",
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T1 - Heterogeneity of anaplastic lymphoma kinase gene rearrangement in non-small-cell lung carcinomas

T2 - A comparative study between small biopsy and excision samples

AU - Abe, Hideyuki

AU - Kawahara, Akihiko

AU - Azuma, Koichi

AU - Taira, Tomoki

AU - Takase, Yorihiko

AU - Fukumitsu, Chihiro

AU - Murata, Kazuya

AU - Yamaguchi, Tomohiko

AU - Akiba, Jun

AU - Ishii, Hidenobu

AU - Okamoto, Isamu

AU - Hoshino, Tomoaki

AU - Takamori, Shinzou

AU - Kage, Masayoshi

PY - 2015/5/30

Y1 - 2015/5/30

N2 - Introduction: The standard diagnostic method for echinoderm microtubule-associated protein-like 4-anaplastic lymphoma receptor tyrosine kinase translocation is fluorescence in situ hybridization (FISH). Recently, immunohistochemistry (IHC) has been reported as a potential method in screening for anaplastic lymphoma kinase (ALK)-positive non-small-cell lung carcinomas (NSCLC), whereas several authors have reported a discordance between FISH and IHC results. We investigated the heterogeneity of ALK gene rearrangement in excision specimens by FISH and also examined whether the FISH score of ALK gene rearrangement corresponded in excision and biopsy samples from the same patient. Methods: Twenty ALK IHC-positive patients including six patients treated with crizotinib therapy were evaluated for the presence of ALK FISH. For evaluation of heterogeneity of ALK gene rearrangement in excision specimens, we defined six to 10 observation areas in each case, and the number of ALK FISH positive observation areas (≥15% rearrangement detected) was investigated. ALK FISH score in small biopsy samples was classified as positive (≥15% rearrangement detected), equivocal (5-14% rearrangement detected), or negative (<4% rearrangement detected). Results: Of a total of 64 tumor observation areas from nine excision specimens, 50 areas were positive for ALK gene rearrangement (81.8%). In the comparison of excision and small biopsy samples, all excision specimens were ALK FISH-positive (100%; 6 of 6), whereas only three of the small biopsy samples in these patients were positive (50%; 3 of 6), two were equivocal (33%; 2 of 6), and one was negative (17%; 1 of 6). The two equivocal patients received crizotinib and showed a response. Conclusion: ALK gene rearrangement heterogeneity was observed in NSCLC specimens by FISH. Our findings suggested that IHC-positive/FISH-equivocal cases should not be considered true "false-negatives" when a small biopsy sample was used for ALK analysis.

AB - Introduction: The standard diagnostic method for echinoderm microtubule-associated protein-like 4-anaplastic lymphoma receptor tyrosine kinase translocation is fluorescence in situ hybridization (FISH). Recently, immunohistochemistry (IHC) has been reported as a potential method in screening for anaplastic lymphoma kinase (ALK)-positive non-small-cell lung carcinomas (NSCLC), whereas several authors have reported a discordance between FISH and IHC results. We investigated the heterogeneity of ALK gene rearrangement in excision specimens by FISH and also examined whether the FISH score of ALK gene rearrangement corresponded in excision and biopsy samples from the same patient. Methods: Twenty ALK IHC-positive patients including six patients treated with crizotinib therapy were evaluated for the presence of ALK FISH. For evaluation of heterogeneity of ALK gene rearrangement in excision specimens, we defined six to 10 observation areas in each case, and the number of ALK FISH positive observation areas (≥15% rearrangement detected) was investigated. ALK FISH score in small biopsy samples was classified as positive (≥15% rearrangement detected), equivocal (5-14% rearrangement detected), or negative (<4% rearrangement detected). Results: Of a total of 64 tumor observation areas from nine excision specimens, 50 areas were positive for ALK gene rearrangement (81.8%). In the comparison of excision and small biopsy samples, all excision specimens were ALK FISH-positive (100%; 6 of 6), whereas only three of the small biopsy samples in these patients were positive (50%; 3 of 6), two were equivocal (33%; 2 of 6), and one was negative (17%; 1 of 6). The two equivocal patients received crizotinib and showed a response. Conclusion: ALK gene rearrangement heterogeneity was observed in NSCLC specimens by FISH. Our findings suggested that IHC-positive/FISH-equivocal cases should not be considered true "false-negatives" when a small biopsy sample was used for ALK analysis.

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