RET-rearranged non-small-cell lung carcinoma

Br J Cancer. 2014 Feb 6. doi: 10.1038/bjc.2014.36. [Epub ahead of print]

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

Tsuta K1, Kohno T2, Yoshida A1, Shimada Y3, Asamura H4, Furuta K1, Kushima R1.

Author information

• 1Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan.
• 21] Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan [2] Division of Translational Research, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Tokyo, Japan.
• 3Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan.
• 4Division of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan.

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.