RET-rearranged non-small-cell lung carcinoma

A clinicopathological and molecular analysis

K. Tsuta, T. Kohno, A. Yoshida, Y. Shimada, Hisao Asamura, K. Furuta, R. Kushima

Research output: Contribution to journalArticle

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Abstract

Background: To elucidate clinicopathological characteristics of non-small-cell lung carcinoma (NSCLC) cases carrying RET rearrangements causing oncogenic fusions to identify responders to therapy with RET tyrosine kinase inhibitors. Methods: We investigated 1874 patients with carcinomas, including 1620 adenocarcinomas (ADCs), 203 squamous cell carcinomas (SCCs), 8 large cell carcinomas, and 43 sarcomatoid carcinomas (SACs). Fluorescence in situ hybridisation (FISH) and/or reverse transcription-PCR (RT-PCR) were performed to detect RET gene rearrangement. Results: In all, 22 cases (1.2%) showed RET rearrangements; all cases were of ADC histology. Of the 22 patients, 19 possessed KIF5B-RET fusion genes, whereas 3 possessed CCDC6-RET fusion genes. The RET-rearranged tumours were significantly more common in younger patients (P=0.038) and tended to occur in patients with no history of smoking (P=0.051). In addition, RET rearrangements were not associated with gender, occupational history (particularly radioactive exposure), tumour size, lymph node status, tumour stage, or patient survival. The predominant growth pattern in RET-rearranged ADCs was lepidic in 6 cases, papillary in 9 cases, acinar in 2 cases, micropapillary in 1 case, and solid in 4 cases. Cells with cytoplasmic mucin production were at least focally present in 12 of the 22 (54.5%) RET-rearranged ADC cases. Among the 21 analysed RET-rearranged tumours, RET immunopositivity was observed in 15 cases (71.4%), and was significantly associated with RET rearrangement (P<0.001). Conclusions: The RET rearrangements were observed in 1.2% of NSCLCs. All cases of RET rearrangement were ADCs. The RET rearrangements were more likely to be observed in younger patients. Although cytoplasmic mucin production was at least focally present in 54.5% of RET-rearranged ADCs, specific histological features were not detected.

Original languageEnglish
Pages (from-to)1571-1578
Number of pages8
JournalBritish Journal of Cancer
Volume110
Issue number6
DOIs
Publication statusPublished - 2014 Mar 18
Externally publishedYes

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Non-Small Cell Lung Carcinoma
Adenocarcinoma
Gene Fusion
Mucins
Neoplasms
Carcinoma
Large Cell Carcinoma
Gene Rearrangement
Fluorescence In Situ Hybridization
Protein-Tyrosine Kinases
Reverse Transcription
Squamous Cell Carcinoma
Histology
Lymph Nodes
Smoking
Polymerase Chain Reaction
Survival
Growth

Keywords

  • adenocarcinoma
  • fluorescence in situ hybridisation
  • immunohistochemistry
  • lung carcinoma
  • RET gene rearrangement

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

RET-rearranged non-small-cell lung carcinoma : A clinicopathological and molecular analysis. / Tsuta, K.; Kohno, T.; Yoshida, A.; Shimada, Y.; Asamura, Hisao; Furuta, K.; Kushima, R.

In: British Journal of Cancer, Vol. 110, No. 6, 18.03.2014, p. 1571-1578.

Research output: Contribution to journalArticle

Tsuta, K, Kohno, T, Yoshida, A, Shimada, Y, Asamura, H, Furuta, K & Kushima, R 2014, 'RET-rearranged non-small-cell lung carcinoma: A clinicopathological and molecular analysis', British Journal of Cancer, vol. 110, no. 6, pp. 1571-1578. https://doi.org/10.1038/bjc.2014.36
Tsuta, K. ; Kohno, T. ; Yoshida, A. ; Shimada, Y. ; Asamura, Hisao ; Furuta, K. ; Kushima, R. / RET-rearranged non-small-cell lung carcinoma : A clinicopathological and molecular analysis. In: British Journal of Cancer. 2014 ; Vol. 110, No. 6. pp. 1571-1578.
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T2 - A clinicopathological and molecular analysis

AU - Tsuta, K.

AU - Kohno, T.

AU - Yoshida, A.

AU - Shimada, Y.

AU - Asamura, Hisao

AU - Furuta, K.

AU - Kushima, R.

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N2 - Background: To elucidate clinicopathological characteristics of non-small-cell lung carcinoma (NSCLC) cases carrying RET rearrangements causing oncogenic fusions to identify responders to therapy with RET tyrosine kinase inhibitors. Methods: We investigated 1874 patients with carcinomas, including 1620 adenocarcinomas (ADCs), 203 squamous cell carcinomas (SCCs), 8 large cell carcinomas, and 43 sarcomatoid carcinomas (SACs). Fluorescence in situ hybridisation (FISH) and/or reverse transcription-PCR (RT-PCR) were performed to detect RET gene rearrangement. Results: In all, 22 cases (1.2%) showed RET rearrangements; all cases were of ADC histology. Of the 22 patients, 19 possessed KIF5B-RET fusion genes, whereas 3 possessed CCDC6-RET fusion genes. The RET-rearranged tumours were significantly more common in younger patients (P=0.038) and tended to occur in patients with no history of smoking (P=0.051). In addition, RET rearrangements were not associated with gender, occupational history (particularly radioactive exposure), tumour size, lymph node status, tumour stage, or patient survival. The predominant growth pattern in RET-rearranged ADCs was lepidic in 6 cases, papillary in 9 cases, acinar in 2 cases, micropapillary in 1 case, and solid in 4 cases. Cells with cytoplasmic mucin production were at least focally present in 12 of the 22 (54.5%) RET-rearranged ADC cases. Among the 21 analysed RET-rearranged tumours, RET immunopositivity was observed in 15 cases (71.4%), and was significantly associated with RET rearrangement (P<0.001). Conclusions: The RET rearrangements were observed in 1.2% of NSCLCs. All cases of RET rearrangement were ADCs. The RET rearrangements were more likely to be observed in younger patients. Although cytoplasmic mucin production was at least focally present in 54.5% of RET-rearranged ADCs, specific histological features were not detected.

AB - Background: To elucidate clinicopathological characteristics of non-small-cell lung carcinoma (NSCLC) cases carrying RET rearrangements causing oncogenic fusions to identify responders to therapy with RET tyrosine kinase inhibitors. Methods: We investigated 1874 patients with carcinomas, including 1620 adenocarcinomas (ADCs), 203 squamous cell carcinomas (SCCs), 8 large cell carcinomas, and 43 sarcomatoid carcinomas (SACs). Fluorescence in situ hybridisation (FISH) and/or reverse transcription-PCR (RT-PCR) were performed to detect RET gene rearrangement. Results: In all, 22 cases (1.2%) showed RET rearrangements; all cases were of ADC histology. Of the 22 patients, 19 possessed KIF5B-RET fusion genes, whereas 3 possessed CCDC6-RET fusion genes. The RET-rearranged tumours were significantly more common in younger patients (P=0.038) and tended to occur in patients with no history of smoking (P=0.051). In addition, RET rearrangements were not associated with gender, occupational history (particularly radioactive exposure), tumour size, lymph node status, tumour stage, or patient survival. The predominant growth pattern in RET-rearranged ADCs was lepidic in 6 cases, papillary in 9 cases, acinar in 2 cases, micropapillary in 1 case, and solid in 4 cases. Cells with cytoplasmic mucin production were at least focally present in 12 of the 22 (54.5%) RET-rearranged ADC cases. Among the 21 analysed RET-rearranged tumours, RET immunopositivity was observed in 15 cases (71.4%), and was significantly associated with RET rearrangement (P<0.001). Conclusions: The RET rearrangements were observed in 1.2% of NSCLCs. All cases of RET rearrangement were ADCs. The RET rearrangements were more likely to be observed in younger patients. Although cytoplasmic mucin production was at least focally present in 54.5% of RET-rearranged ADCs, specific histological features were not detected.

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KW - immunohistochemistry

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KW - RET gene rearrangement

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