RET-rearranged non-small-cell lung carcinoma: a clinicopathological and molecular analysis

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 1...

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Bibliographic Details
Published in:British journal of cancer 2014-03, Vol.110 (6), p.1571-1578
Main Authors: Tsuta, K, Kohno, T, Yoshida, A, Shimada, Y, Asamura, H, Furuta, K, Kushima, R
Format: Article
Language:English
Subjects:
692/699/67/1612/1350
692/699/67/68
692/700/139/422
Adenocarcinoma - genetics
Adenocarcinoma - pathology
Adenocarcinoma of Lung
Adult
Aged
Aged, 80 and over
Biomedical and Life Sciences
Biomedicine
Cancer Research
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - pathology
Clinical trials
Drug Resistance
Epidemiology
Female
Gene Rearrangement
Genes
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Kinases
Lung cancer
Lung Neoplasms - genetics
Lung Neoplasms - pathology
Male
Medical research
Middle Aged
Molecular Medicine
molecular-diagnostics
Oncology
Proteins
Proto-Oncogene Proteins c-ret - genetics
Reverse Transcriptase Polymerase Chain Reaction
Survival Analysis
Thoracic surgery
Tumors
Young Adult
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Summary: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
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.2014.36