ALK, ROS1 and RET rearrangements in lung squamous cell carcinoma are very rare

Zhao, Weijie; Choi, Yoon‐La; Song, Ji-Young; Zhu, Yazhen; Xu, Qing; Feng, Zhenqing; Jiang, Lili; Cheng, Ju; Zheng, Guangjuan; Mao, Mao

doi:10.1016/j.lungcan.2016.01.011

Cited by 56 publications

(40 citation statements)

References 45 publications

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“…While TaqMan RQ‐PCR is the most sensitive method used in clinic to detect fusion transcripts in leukemia, we further validated the fusion transcripts status in all the cases by TaqMan RQ‐PCR and found that NanoString has superior accuracy and sensitivity and comparable specificity compared to RT‐PCR. In addition to our study, the use of NanoString in detecting gene translocations/fusion transcripts has been reported in lung cancer studies and good concordance between NanoString and FISH or immunohistochemistry has been shown . Our study offered the first report to compare NanoString with a multiplexed RT‐PCR clinical assay, and the results supported that NanoString can serve as a valuable alternative or even superior method to RT‐PCR for initial screening/quantitation of leukemogenic fusion transcripts in the diagnosis of de novo AML.…”

Section: Discussionsupporting

confidence: 78%

“…While the application of NanoString in basic and translational research has become increasingly popular , use of this platform at clinic for purposes of diagnosis or prognosis is still in its infancy stage. So far, the only commercially available clinical assay on NanoString platform is the PAM50 Breast Cancer Gene Assay, which measures the expression levels of 50 genes in a multiplexed fashion to provide prognostic and predictive information for early‐stage breast cancer .…”

Section: Introductionmentioning

confidence: 99%

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Development of a NanoString assay to detect leukemogenic fusion transcripts in acute myeloid leukemia

Zhou

Wang

et al. 2016

Int J Lab Hematology

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Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Development of a NanoString assay to detect leukemogenic fusion transcripts in acute myeloid leukemia

Zhou

Wang

et al. 2016

Int J Lab Hematology

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“…Research has reported that two genes in particular (human epidermal growth factor receptor [ EGFR ] and anaplastic lymphoma kinase [ ALK ]) are associated with improvements in therapeutic efficiency in non-small cell lung cancer patients receiving targeted therapies. ALK fusion genes are typically identified in approximately 5.0% of patients with lung adenocarcinoma, although they are rare in patients with squamous cell carcinoma (SqCC) [1, 2]. Treatment of metastatic ALK -rearranged non-small cell lung cancer with ALK inhibitors leads to higher response rates and improved progression-free survival relative to conventional chemotherapy regimens [3, 4].…”

Section: Introductionmentioning

confidence: 99%

ALK-rearranged lung squamous cell carcinoma responding to alectinib: a case report and review of the literature

et al. 2017

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BackgroundAlthough anaplastic lymphoma kinase (ALK) fusion genes are generally identified in lung adenocarcinoma patients, they are relatively rare in patients with squamous cell carcinoma (SqCC). Metastatic ALK-rearranged lung adenocarcinoma patients treated with ALK inhibitors demonstrate higher response rates, improved progression-free survival, and reduced toxicity relative to those treated with conventional chemotherapy regimens. However, the efficacy of treatment with ALK inhibitors in patients with ALK-rearranged lung SqCC remains unknown.Case presentationWe discuss a 52-year-old Japanese-Brazilian woman without a history of smoking who was referred to our hospital for evaluation of severe left back pain and a left hilar mass observed on a chest radiograph. The patient was eventually diagnosed on the basis of computed tomography, pathological, and immunohistochemical findings as having Stage IV lung SqCC. First-line treatment with palliative radiotherapy and systemic chemotherapy with cisplatin plus vinorelbine was administered, but was not effective. ALK testing was subsequently performed, revealing positive ALK expression and gene rearrangement. Alectinib therapy was then initiated, which resulted in a gradual, but substantial reduction in tumor size.ConclusionsTo the best of our knowledge, this is the first case report to discuss the successful management of ALK-rearranged lung SqCC with alectinib. We propose that molecular testing for driver mutations should be considered in young patients with a light or no smoking history, even if the histological findings correspond with SqCC, and alectinib therapy represents a reasonable option in cases of ALK-rearranged lung SqCC.

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“…But actually Rekhtman et al found that only 5.4% lung adenocarcinomas co-express TTF-1and p63 in general [30], even less for TTF1 and p40 co-expression. Zhao et al found that ALK , ROS1 or RET gene rearrangements appeared 0 times in 214 cases of lung squamous cancer [31], suggesting that the prevalence of ROS1 rearrangement is very low in SCC histology. We suppose that histology of ROS1 + lung cancer has low differentiation with peculiar immunoprofile, which may indicate that the cell of origin of ROS1 + lung adenocarcinoma may different from most lung adenocarcinomas.…”

Section: Discussionmentioning

confidence: 99%

Advanced lung adenocarcinomas with ROS1-rearrangement frequently show hepatoid cell

et al. 2016

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Defining distinctive histologic characteristics of ROS1-rearranged non-small-cell lung carcinomas (NSCLCs) may help identify cases that merit molecular testing. However, the majority of previous reports have focused on surgical specimens but only limited studies assessed histomorphology of advanced NSCLCs. In order to identify the clinical and histological characteristics of ROS1-rearranged advanced NSCLCs, we examined five hundred sixteen Chinese patients with advanced NSCLCs using ROS1 fluorescence in situ hybridization and real-time polymerase chain reaction and then analyzed for clinical and pathological features. We performed univariate and multivariate analyses to identify predictive factors associated with ROS1 rearrangement. 19 tumors were identified with ROS1 rearrangement (3.7% of adenocarcinomas). 16 ROS1+ and 122 ROS1- samples with available medical records and enough tumor cells were included for histological analysis. Compared with ROS1-negative advanced NSCLCs, ROS1-rearranged advanced NSCLCs were associated with a younger age at presentation. ROS1 rearrangements were not significantly associated with sex, smoking history, drinking history and metastatic sites. The most common histological pattern was solid growth (12/16), followed by acinar (4/16) growth. 66.7% cases with solid growth pattern showed hepatoid cytology (8/12) and 75% cases with acinar growth pattern showed a cribriform structure (3/4). 18.8% cases were found to have abundant extracellular mucus or signet-ring cells (3/16). Only one case with solid growth pattern showed psammomatous calcifications. In conclusion, age, hepatoid cytology and cribriform structure are the independent predictors for ROS1-rearranged advanced NSCLCs, recognizing these may be helpful in finding candidates for genomic alterations, especially when available tissue samples are limited.

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ALK, ROS1 and RET rearrangements in lung squamous cell carcinoma are very rare

Cited by 56 publications

References 45 publications

Development of a NanoString assay to detect leukemogenic fusion transcripts in acute myeloid leukemia

Development of a NanoString assay to detect leukemogenic fusion transcripts in acute myeloid leukemia

ALK-rearranged lung squamous cell carcinoma responding to alectinib: a case report and review of the literature

Advanced lung adenocarcinomas with ROS1-rearrangement frequently show hepatoid cell

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