Biology

Fish <Actinopterygii>

Fishery

Lung cancer

Computer science

Malignant pleural effusion

Anaplastic lymphoma kinase

False positive paradox

Oncology

Medicine

Immunohistochemistry

Machine learning

Pathology

Journal of Thoracic Oncology

ALK activation is generally produced due to formation of fusion genes involving EML4, being described in 3 to 10% of NSCLC. ALK+ tumors present more frequently in young, non smoker patients, with female predominance and are generally adenocarcinomas. ALK alterations have been described in all clinical and pathologic subtypes and these should not be the sole indicators to search for the fusion. This determination describes a subgroup with different biological behavior and effective directed therapy. The ALK Break Apart FISH Probe Kit (Abbott Molecular, Des Plaines, IL) and the VENTANA ALK (D5F3) CDx Assay has become an FDA-approved companion diagnostic for targeted therapy. The FISH assay is fraught with technical challenges; including FISH signal instability and scoring difficulties. Consequently, the assay is prone to false negatives and false positives. Two case reports are presented with different diagnostic results in ALK status by IHC and FISH and diverse clinical responses to directed therapy. ALK IHC testing was performed using the Ventana anti-ALK (D5F3) Rabbit monoclonal antibody (Roche, CE-IVD) used in combination with the OptiView DAB IHC Detection kit and OptiView Amplification Kit as a fully automated IHC assay on the Ventana BenchMark XT automated slide stainer. ALK FISH testing was performed using the Vysis ALK Break Apart Probe kit (2p23/ALK translocation detection, Abbott, CE-IVD). We examined 308 NSCLC cases and compared the FISH results to ALK IHC. Of 8 (3%) cases identified as positive expression, only 6 have ALK rearrangement. Case 1: 54 years old male, 30 pack/year smoker, evaluated in October 2015 presenting fever and cough. CT shows pulmonary mass infiltrating mediastinum and pulmonary artery and enlarged ganglionar groups 5, 6 and 7. Supraclavicular node biopsy informs moderately differenciated adenocarcinomas. PET demonstrates FDG positivity in retroperitoneal image in left diaphragmatic crus. Being defined as stage IV, he starts chemotherapy with cisplatin and pemetrexed. After first cycle, ALK+ result by IHC is obtained changing treatment to Crizotinib. Further tests revealed no ALK gene rearrangement. After 60 days of treatment CT evaluation evidences disease progression switching to chemotherapy regimen. Case 2:61 year old female smoker (18 pack/year) is diagnosed by thorax CT of a left inferior lobe mass and satellite nodal image. PET scan informs increased uptake in mediastinum nodes and pulmonary peripheral nodules. Detection of a moderately differenciated adenocarcinomas with parietal pleura and ganglionar groups 5-6 involvement is accomplished by percutaneous biopsy and mediastinoscopy. Pathologic assessment highlights ALK+ by IHC starting treatment with Crizotinib which continues at present. ALK FISH testing demonstrated no ALK gene rearrangement. Partial response is described in CT evaluation in May 2016. Although FISH is the gold standard to detect ALK positive patients this two cases with different response in ALK IHC positive FISH negative points out the absence of guidelines in this rare scenario.

P2.12: Treatment Response in Patients With ALK Immunohistochemistry (IHC) Positive With Fish Negative