Immunohistochemical screening for anaplastic lymphoma kinase (ALK) rearrangement in advanced non-small cell lung cancer patients

Park, Heae Surng; Lee, Jake June-Koo; Kim, Dong Wan; Kulig, Kimary; Kim, Tae Min; Lee, Se‐Hoon; Jeon, Yoon Kyung; Chung, Doo Hyun; Heo, Dae Seog

doi:10.1016/j.lungcan.2012.03.004

Cited by 103 publications

(83 citation statements)

References 25 publications

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“…Since ALK was negative by FISH in this case, the result of ICC seemed to be accurate. Some reports indicated that IHC weak positive case did not match the result of FISH [11,19,20]. In the present study, ICC and IHC score 2+ cases showed full match results.…”

Section: Discussioncontrasting

confidence: 60%

Clinical application of immunocytochemical detection of ALK rearrangement on cytology slides for detection or screening of lung adenocarcinoma

et al. 2013

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Immunohistochemical screening of Anaplastic lymphoma kinase (ALK) rearrangement has been regarded essential and routinely carried out to select treatment for lung adenocarcinoma. However, difficulty to approach a tumor by transbronchial lung biopsy (TBLB), it often fails to obtain tumor tissues whereas tumor cells are contained in cytology specimens simultaneously obtained when the bronchoscopy is done. Therefore we evaluated the expression of ALK protein by using immunohistochemistry (IHC) on TBLB specimens and immunocytochemistry (ICC) on brushing smear cytology slides in the same cases, and compared the concordance rate of IHC and ICC results. ICC was carried out on routine Papanicolau-stained slides after cytology diagnosis and decolorization.Results: Eighteen patients with adenocarcinoma were extracted in the Hirosaki University Hospital and the Hirosaki National Hospital. IHC and ICC results showed a very high concordance rate: sensitivity of ICC in comparison with IHC was 85.7% (6/7), specificity was 100% (11/11), 3 positive predictive value was 100% (6/6), and negative predictive value was 91.6% (11/12). Detection of ALK rearrangement using ICC on routine Papanicolau cytology slides is considered to be advantageous for lung cancer treatments.

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Section: Discussioncontrasting

confidence: 60%

Clinical application of immunocytochemical detection of ALK rearrangement on cytology slides for detection or screening of lung adenocarcinoma

et al. 2013

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“…27,37 However, many subsequent studies reported that ALK immunohistochemistry is a highly sensitive method with a significant correlation with ALK FISH using a number of antibodies including the ALK1, 5A4 and D5F3 clones. 15,19,28,31,34,[38][39][40][41] Apart from our study, only one prior group has investigated the performance of all three antibodies in the same patient population, 34 in which they found a very similar incidence of ALK rearrangement (1%) and one false-negative result using the ALK1 antibody. Many studies have reported ALK immunohistochemistry as a useful method for confirming ALK translocation by FISH.…”

Section: Discussionmentioning

confidence: 99%

Testing for ALK rearrangement in lung adenocarcinoma: a multicenter comparison of immunohistochemistry and fluorescent in situ hybridization

et al. 2013

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Rearrangements of anaplastic lymphoma kinase (ALK) gene in non-small cell lung cancer (NSCLC) define a molecular subgroup of tumors characterized clinically by sensitivity to ALK tyrosine kinase inhibitors such as crizotinib. Although ALK rearrangements may be detected by reverse transcriptase-PCR, immunohistochemistry or fluorescence in situ hybridization (FISH), the optimal clinical strategy for identifying ALK rearrangements in clinical samples remains to be determined. We evaluated immunohistochemistry using three different antibodies (ALK1, 5A4 and D5F3 clones) to detect ALK rearrangements and compared those with FISH. We report the frequency and clinicopathologic features of lung cancers harboring ALK translocations in 594 resected NSCLCs (470 adenocarcinomas; 83 squamous carcinomas, 26 large cell carcinomas and 15 other histological subtypes) using a tissue microarray approach. We identified an ALK gene rearrangement in 7/594 cases (1%) by FISH and all anti-ALK antibodies correctly identified the seven ALK-positive cases (100% sensitivity), although the intensity of staining was weak in some cases. These data indicate that the use of antibodies with high sensitivity and avidity to ALK may provide an effective pre-screening technique to complement the more expensive and labor-intensive approach of ALK FISH testing.

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“…ERBB2 expression was scored from 0 to 3+ according to the FDAapproved guidelines for the HercepTest and cases with scores of 2+ or 3+ were considered positive for expression. 28 In brief, cases with separate green and red signals and/or isolated red signals in ≥ 15% of tumor cells were considered to harbor an ALK translocation. EGFR gene copy number was estimated using an LSI EGFR SpectrumOrange/CEP7 SpectrumGreen probe set (Abbott Molecular) and interpreted according to the University of Colorado Cancer Center system as described previously.…”

Section: Patients and Samplesmentioning

confidence: 99%

Clinicopathologic analysis of programmed cell death-1 and programmed cell death-ligand 1 and 2 expressions in pulmonary adenocarcinoma: comparison with histology and driver oncogenic alteration status

et al. 2015

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Immunotherapies targeting the programmed cell death-1/programmed cell death-ligand 1 pathway have emerged as promising therapeutic strategies for lung cancer. However, the expression pattern and prognostic implications of programmed cell death-ligand 1 and 2 and programmed cell death-1 in comparison with the histology and genetic alterations in pulmonary adenocarcinomas remains unclear and thus were addressed here. Programmed cell death-ligand 1 and 2 expression in tumor cells and the quantities of programmed cell death-1 + and CD8 + tumor-infiltrating lymphocytes were immunohistochemically evaluated in 497 resected pulmonary adenocarcinomas and analyzed according to clinicopathological and genetic statuses. Programmed cell death-ligand 1 and 2 expression were observed in 59% and 64% of pulmonary adenocarcinomas, respectively, and showed a strong positive correlation with each other (Po 0.001). Programmed cell death-ligand 1 expression was higher in nodal metastasis cases (P = 0.006), smokers (P = 0.056), poorly differentiated tumors and histologic subtypes of solid and micropapillary patterns (Po0.001). There was no significant difference in programmed cell death-ligand 1 and 2 expression according to EGFR mutation status. However, programmed cell death-ligand 1 expression was correlated with ALK translocation (P = 0.054) and expression of EGFR and MET (Po 0.001). Meanwhile, programmed cell death-ligand 2 expression was correlated with ALK translocation (P = 0.052), and expression of MET (Po 0.001) and ERBB2 (P = 0.013). The numbers of CD8 + and programmed cell death-1 + lymphocytes were higher in smokers (P = 0.012 and 0.016) and MET-expressing adenocarcinomas (Po 0.001). Patients expressing programmed cell death-ligand 1 and/or high ratios of programmed cell death-1 + /CD8 + lymphocytes showed shorter disease-free survival (P = 0.001). Our study demonstrated that programmed cell death-ligand 1 and 2 expression varied with histology, EGFR, ALK, MET, and ERBB2 statuses, and activation of the programmed cell death-1/programmed cell death-ligand 1 pathway may be a poor prognostic factor in pulmonary adenocarcinomas.

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Immunohistochemical screening for anaplastic lymphoma kinase (ALK) rearrangement in advanced non-small cell lung cancer patients

Cited by 103 publications

References 25 publications

Clinical application of immunocytochemical detection of ALK rearrangement on cytology slides for detection or screening of lung adenocarcinoma

Clinical application of immunocytochemical detection of ALK rearrangement on cytology slides for detection or screening of lung adenocarcinoma

Testing for ALK rearrangement in lung adenocarcinoma: a multicenter comparison of immunohistochemistry and fluorescent in situ hybridization

Clinicopathologic analysis of programmed cell death-1 and programmed cell death-ligand 1 and 2 expressions in pulmonary adenocarcinoma: comparison with histology and driver oncogenic alteration status

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