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Oncol Lett
2015 Apr 01;94:1537-1540. doi: 10.3892/ol.2015.2897.
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Response to erlotinib in a patient with lung adenocarcinoma harbouring the EML4-ALK translocation: A case report.
Alì G
,
Chella A
,
Lupi C
,
Proietti A
,
Niccoli C
,
Boldrini L
,
Davini F
,
Mussi A
,
Fontanini G
.
Abstract
Lung cancer is the leading cause of cancer-associated mortality worldwide, and the mainstay of treatment remains to be personalised therapy. Tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR-TKIs) have been reported to exert a significant impact in the treatment of non-small cell lung cancer (NSCLC), particularly in patients harbouring mutations in the EGFR gene. The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) gene translocation has been described in a subset of patients with NSCLC and possesses potent oncogenic activity. This translocation represents one of the most novel molecular targets in the treatment of NSCLC. Patients who harbour the EML4-ALK rearrangement possess lung tumours that lack EGFR or K-ras mutations. The present study reports the case of a patient possessing the EML4-ALK rearrangement that was initially treated with erlotinib and achieved a lasting clinical response. To the best of our knowledge, the current study is the first report of a clinical response to EGFR-TKI in a patient with lung adenocarcinoma harbouring the EML4-ALK fusion gene, but no EGFR mutations. However, as the disease progressed, the ALK gene status of the tumour was investigated, and based upon a positive result, the patient was treated with crizotinib and achieved a complete response. In conclusion, the present study suggests that the EML4-ALK rearrangement is not always associated with resistance to EGFR-TKIs. Further studies are required to clarify the biological features of these tumours and to investigate the mechanisms underlying the primary resistance to EGFR-TKIs when the EML4-ALK rearrangement is present.
Figure 1. Lung adenocarcinoma exhibiting a mucinous growth pattern, areas of papillary pattern and signet ring cell features (magnification, ×10).
Figure 2. (A) Thoracic computed tomography (CT) revealing a sub-centimetre lesion, 8.0 mm in diameter, in the lower lobe of the left lung that (B) demonstrated a small increase in size after 17 months. (C) CT scan revealed progression with an increase in the size of the lesions of the left lung and (D) demonstrated a partial response following four cycles of chemotherapy with cisplatin and pemetrexed.
Figure 3. (A) Fluorescence in situ hybridisation analysis of the lung tumour specimen revealing cells with characteristic ALK translocation identified by one normal (paired) signal and two pairs of separated signals (arrows) (magnification, ×100). (B) Immunohistochemical staining for the ALK protein revealing strong granular cytoplasmic expression in the lung adenocarcinoma specimen (magnification, ×10). ALK, anaplastic lymphoma kinase.
Figure 4. Comparison of (A) the initial computed tomography (CT) of the thorax and (B) the repeat CT three months after initiation of crizotinib therapy, demonstrating the dramatic shrinkage of the tumour lesions.
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