Anaplastic lymphoma kinase status in lung cancers: An immunohistochemistry and fluorescence in situ hybridization study from a tertiary cancer center in India

2017 ◽  
Vol 54 (1) ◽  
pp. 231
Author(s):  
SS Murthy ◽  
SJ Rajappa ◽  
SD Gundimeda ◽  
KM Mallavarapu ◽  
S Ayyagari ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Anaplastic Lymphoma Kinase ◽  
Cancer Center ◽  
Hybridization Study ◽  
Lung Cancers ◽  
Anaplastic Lymphoma ◽  
Tertiary Cancer Center

scholarly journals Molecular epidemiological study of microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene using immunohistochemistry as a cost effective alternative to fluorescence in situ hybridization for Indian patients with adenocarcinoma lung

2017 ◽  
Vol 03 (01) ◽  
pp. 045-049
Author(s):  
Anurag Mehta ◽  
Ullas Batra
Keyword(s):  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Epidemiological Study ◽  
Anaplastic Lymphoma Kinase ◽  
Fusion Gene ◽  
Cost Effective ◽  
Gene Fusions ◽  
Anaplastic Lymphoma ◽  
Cost Effective Alternative

Abstract Background: With fluorescence in situ hybridization (FISH) as the main-stay for the detection of anaplastic lymphoma kinase (ALK) rearrangements, the ALK Break Apart FISH Probe Kit has become a Food and Drug Association-approved companion diagnostic for targeted therapy with the ALK inhibitor crizotinib in lung cancers. The objective of this molecular epidemiological study was to estimate the prevalence of microtubule-associated protein-like 4-ALK (EML4-ALK) fusion gene using immunohistochemistry (IHC) as a cost effective alternative to FISH for Indian patients with nonsmall-cell cancer (NSCC)-adenocarcinoma, favor adenocarcinoma lung and NSCC- Not otherwise specified (NOS). Materials and Methods: Patients with NSCC-adenocarcinoma, favor adenocarcinoma lung, and nonsmall cell lung cancer-NOS histology were considered for this study. Permission was obtained from the Ethics Committee before the start of the study. Clinical characteristics and treatment details were collected from the patient's medical records. IHC analysis was performed using a Ventana automated immunostainer (Benchmark XT). Detection was performed using OptiView DAB Detection and Amplification Kit. Results: A total of 200 NSCC-adenocarcinoma, favour adenocarcinoma and NSCC-NOS patients were included in the study. There were 122 (61%) men and 78 (39%) women with a median age of 57 years. Of the 200 patients, 43 (21.5%) were nonsmokers and 175 (87.5%) had Stage-IV disease at the time of initial diagnosis. 48 (24%) cases were positive for epidermal growth factor receptor mutations, whereas EML4-ALK fusion gene was present in 27 (13.5%) patients. 25 of the 27 patients with ALK positivity received crizotinib therapy. Conclusions: The incidence of EML4-ALK gene fusions (13.5%) in this Indian population is four-fold high than the previous reported incidences and supports the claim of several recent studies that a relatively new ALK clone, 5A4, and D5F3 from Leica/Novocastra and cell signaling technology/Ventana, respectively can accurately identify ALK rearranged lung adenocarcinoma. The inclusion of IHC for the detection of EML4-ALK gene fusions as a low cost alternative seems justified in low resource setting.

ALK-1 Protein Expression and ALK Gene Rearrangements Aid in the Diagnosis of Inflammatory Myofibroblastic Tumors of the Female Genital Tract

2012 ◽  
Vol 136 (6) ◽  
pp. 623-626 ◽  
Author(s):  
Neil E. Fuehrer ◽  
Gary L. Keeney ◽  
Rhett P. Ketterling ◽  
Ryan A. Knudson ◽  
Debra A. Bell
Keyword(s):  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Anaplastic Lymphoma Kinase ◽  
Genital Tract ◽  
Female Genital Tract ◽  
Gene Rearrangements ◽  
Anaplastic Lymphoma ◽  
Inflammatory Myofibroblastic Tumors ◽  
Female Genital

Context.—Inflammatory myofibroblastic tumor is a predominantly benign, spindle cell, mesenchymal neoplasm with myxoid areas that occurs rarely in the female genital tract and may be confused with other spindle cell lesions, particularly leiomyosarcoma. Objective.—To investigate the utility of detecting anaplastic lymphoma kinase-1 protein expression and ALK gene rearrangements in the diagnosis of inflammatory myofibroblastic tumors in the female genital tract. Design.—Eight inflammatory myofibroblastic tumors arising in the female genital tract and seen in consultation (from 2004 to 2011) were reviewed. Immunohistochemistry for anaplastic lymphoma kinase-1 and fluorescence in-situ hybridization studies for ALK gene rearrangements were performed. Results.—The anatomic sites included myometrium (4 cases) and endometrium, fallopian tube, cervix, and a cervical polyp (1 each), with a patient age range from 25 to 52 years. Histologic features ranged from bland spindle cells to striking cytologic atypia, embedded in a prominent myxoid background. Anaplastic lymphoma kinase-1 immunohistochemistry was positive in 7 cases. Fluorescence in-situ hybridization studies detected ALK gene rearrangements in 5 cases. Five cases had both immunopositivity and fluorescence in-situ hybridization abnormalities, 2 cases had immunopositivity only, and 1 case was negative by both methods. Conclusions.—This is the first report, to our knowledge, of ALK gene rearrangements in inflammatory myofibroblastic tumors in the female genital tract. If a myxoid background is appreciated in a spindle cell lesion of the female genital tract, especially if inflammatory cells are present, anaplastic lymphoma kinase-1 staining along with fluorescence in situ hybridization studies, for ALK gene rearrangements, may aid in distinguishing inflammatory myofibroblastic tumors from their malignant mimics.

scholarly journals Discordance between Fluorescence In Situ Hybridization and Immunohistochemistry Analysis of Anaplastic Lymphoma Kinase Rearrangement in Indian Patients with Non-Small Cell Lung Cancer

2020 ◽  
Vol 9 (02) ◽  
pp. 109-114
Author(s):  
Manish Kumar ◽  
Kishore Kumar ◽  
Harinder Pal Singh ◽  
Suresh Nair ◽  
Amol Patel ◽  
...  
Keyword(s):  
Lung Cancer ◽  
In Situ Hybridization ◽  
Pleural Effusion ◽  
Brain Metastasis ◽  
Fluorescence In Situ Hybridization ◽  
Cell Lung Cancer ◽  
Anaplastic Lymphoma Kinase ◽  
Alk Rearrangement ◽  
Anaplastic Lymphoma

Abstract Aims This study aims to evaluate the incidence of anaplastic lymphoma kinase (ALK) mutation in nonsmall cell lung cancer (NSCLC) incorporating fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) methods and to look for any discordance. Methods We evaluated 101 samples obtained from an enriched cohort of NSCLCs patients from the Army Hospital Research and Referral, New Delhi, India, between November 2016 and November 2018. IHC was performed using the highly-sensitive D5F3 rabbit monoclonal primary antibody. FISH was performed with dual-color, break-apart probe (ZytoLight SPEC) on formalin-fixed, and paraffin-embedded tissue. Discordance between IHC and FISH for ALK rearrangements was evaluated. Pearson correlation coefficient (r) was performed to identify any association of ALK presence (by IHC and FISH) with smoking brain metastasis, programmed death-ligand (PD-L1) expression, pleural effusion, and histopathological subtype. Results A total of 7.92% (8/101) cases tested by IHC and 9.9% (10/101) cases tested by FISH were positive for ALK rearrangement. Of 93 ALK IHC-negative cases, 4 were ALK FISH-positive, whereas of 91 ALK FISH-negative cases, 4 were ALK IHC-positive cases. The correlation analysis demonstrated no or very weak correlation in ALK mutations by IHC or FISH with smoking, brain metastasis, PD-L1 expression, pleural effusion, and histopathological examination, except a weak positive correlation (r = 0.33) observed between brain metastasis and ALK rearrangement identified by FISH. Conclusions Our study demonstrated a somewhat similar incidence of ALK FISH-positive cases and ALK IHC-positive cases, though the incidence was numerically higher for ALK-FISH method.

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