Clinicopathologic characteristics of ALK rearrangements in primary lung adenocarcinoma with identified EGFR and KRAS status

Wang, Jinghui; Dong, Yujie; Cai, Yiran; Zhou, Lijuan; Wu, Shafei; Liu, Guimei; Su, Dan; Li, Xi; Qin, Na; Nong, Jingying; Jia, Hongyan; Zhang, Quan; Mu, Jing; Zhang, Xuan; Zhang, Haiqing; Zhang, Shucai; Zhang, Zongde

doi:10.1007/s00432-014-1584-8

Cited by 32 publications

(28 citation statements)

References 28 publications

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“…Previous studies have reported that the frequency of the ALK rearrangements in NSCLCs using FISH ranged from 3 to 13% [34,35,36,37,38]. Values of 3-11% ALK positivity were found for the Chinese population in several studies [22,39,40,41,42], with the inconsistency reported resulting from factors including the methodology used to detect the ALK rearrangements and the patients enrolled in the studies. Our results for ALK rearrangements are consistent with these previous studies.…”

Section: Discussionmentioning

confidence: 96%

Mutational Profile and New IASLC/ATS/ERS Classification Provide Additional Prognostic Information about Lung Adenocarcinoma: A Study of 125 Patients from Brazil

Melo

Sá²,

Sternberg

et al. 2015

Oncology

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Aim: To show additional prognostic information about the mutational profile and new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification of adenocarcinoma (ADC) in patients without epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor treatments. Methods: In human lung ADC patients (n = 125), including 24 lepidic, 67 acinar, 23 papillary, and 11 solid predominant subtypes, EGFR and KRAS were sequenced, and anaplastic lymphoma kinase (ALK) rearrangements were screened using fluorescence in situ hybridization (FISH). Results:EGFR was mutated in 21.6% of patients with 19.57% showing a mean expression. The most frequent EGFR mutation was a deletion in exon 19, followed by an L858R amino acid substitution in exon 21. KRAS was mutated in 26.4% of patients with 50% displaying mean expression. ALK rearrangement was detected in 6 patients (4.8%). Predominant acinar ADC was strongly associated with EGFR and KRAS mutation. Clinical stage, lymph node metastases, and EGFR mutation in exon 18 showed a significant difference in disease-free and overall survival, but only a trend significance for EGFR and KRAS mutations. Multivariate analysis revealed that men aged >71 years, with a history of smoking (<72 packs/year), clinical stage I/II, and acinar histologic subtype presented better survival than women aged ≤71 years, with a history of smoking (>72 packs/year), and having a predominant solid ADC and EGFR mutation in exon 18. Conclusions: These results indicate that the mutational profile and new IASLC/ATS/ERS classification provide additional prognostic information about lung ADC.

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Section: Discussionmentioning

confidence: 96%

Mutational Profile and New IASLC/ATS/ERS Classification Provide Additional Prognostic Information about Lung Adenocarcinoma: A Study of 125 Patients from Brazil

Melo

Sá²,

Sternberg

et al. 2015

Oncology

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“…Numerous studies have identified the associations between EGFR mutations and the predominant subtypes subsequent to the publication of the novel IASLC/ATS/ERS classification. Wang et al (26) examined 332 patients with primary LAC, and 149 patients (44.9%) were found to harbor EGFR mutations; the EGFR mutation rate was significantly increased in the papillary predominant subtype compared with the solid predominant subtype with mucin production (P=0.008). Song et al (24) reviewed 161 patients who underwent surgical resections, and EGFR mutation was examined in 67 cases (41.6%).…”

Section: Discussionmentioning

confidence: 99%

“…Wang et al (26) did not identify any significant differences in histological subtypes between the KRAS mutations and the wild-types; whereas, Yoshizawa et al (14) and Kakegawa et al (28) indicated that KRAS mutations were significantly associated with adenocarcinoma of mucinous tumor subtypes (P<0.001). Rekhtman et al (29) showed that KRAS mutations occurred more often in adenocarcinomas with a solid growth pattern (P=0.022).…”

Section: A B C D E Fmentioning

confidence: 97%

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Association between the histological subtype of lung adenocarcinoma, EGFR/KRAS mutation status and the ALK rearrangement according to the novel IASLC/ATS/ERS classification

et al. 2016

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Abstract. The present study aimed to investigate the association between epidermal growth factor receptor (EGFR)/Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangements and the morphological characteristics of lung adenocarcinoma (LAC), according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification in a large group of patients with primary LAC. A total of 200 patients with invasive LAC who had undergone complete resections at the Beijing Chest Hospital (Beijing, China) were randomly selected. The morphology of the samples was reassessed in 5% increments by two pathologists, according to the IASLC/ATS/ERS scheme. EGFR and KRAS mutations were tested by direct DNA sequencing. ALK rearrangements were screened by immunohistochemistry on a Benchmark XT stainer. The data revealed that EGFR and KRAS mutations, and ALK rearrangements were identified in 46.0% (92/200), 9.0% (18/200) and 11.5% (23/200) of the patients, respectively. The EGFR/KRAS mutations and ALK rearrangements were mostly exclusive. However, 1 patient exhibited the coexistence of the EGFR (at exon 20) and KRAS (codon 12) mutations, and another patient exhibited the coexistence of the EGFR mutation (at exon 21) and the ALK gene fusion. EGFR mutations were indicated to be closely associated with the acinar predominant (43/77; 55.8%; P=0.030) and papillary predominant (26/49; 53.1%; P=0.006) subtypes. KRAS mutations were more commonly associated with the solid predominant subtype (9/52; 17.3%; P=0.023) and invasive mucinous LAC (5/10; 50.0%; P=0.004), and less commonly associated with the acinar predominant subtype (1/77; 1.3%; P=0.002). ALK rearrangements more commonly occurred in the solid predominant subtype compared with other subtypes (13/52; 25%; P=0.002), and less commonly occurred in the papillary predominant subtype (1/49; 2.0%; P=0.004). Tumors harboring ALK rearrangements were characterized by signet-ring cell (7/9; 77.8%; P<0.0001) and cribriform (7/12; 58.3%; P<0.0001) patterns. The association between the mutation status and histological subtype in LAC was distinct. The predominant subtype according to the IASLC/ATS/ERS classification provided important information for gene mutations and integrated clinical findings to improve the treatment of LAC patients.

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“…EML4-ALK rearrangement was reported as a relatively low frequent rearrangement ranging from 1.5% to 6.7% among unselected Caucasian NSCLC patients (14)(15)(16)(17). It seems to have higher frequency in Asian population, and was reported as high as 5.1-10% (18)(19)(20)(21). Part of the explanation was that in those studies, patients were selected from EGFR wild population.…”

Section: Discussionmentioning

confidence: 99%

High concordance of ALK rearrangement between primary tumor and paired metastatic lymph node in patients with lung adenocarcinoma

Hou

Ren

Su³

et al. 2016

J. Thorac. Dis.

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Background: Lung cancer has heterogeneous features. It remains unclear whether ALK rearrangement was distributed heterogeneously in tumor from different anatomic sites. To address this issue, we investigate the concordance of ALK rearrangement between primary tumors and paired metastatic lymph nodes in pulmonary adenocarcinoma patients. Results: A total of 101 patients were enrolled into this study with a median age of 60 years old (range, 35-78 years). ALK rearrangement was found in 20 primary lesions, while in 18 paired metastatic lymph nodes. ALK rearrangement was more frequently happened in younger (P<0.001), Nonsmokers (P=0.012), high-stage disease (P=0.021) and predominantly solid growth pattern (P=0.024). The concordance rate between primary tumor and paired metastatic lymph nodes was 98%. Two patients with ALK rearrangement on primary tumor didn't show ALK gene fusion on paired metastatic lymph nodes. Sixty-eight cases had more than two stations of metastatic lymph nodes. ALK rearrangement in the different station of metastatic lymph nodes of the same patient was consistent.Conclusions: High concordant rate of ALK rearrangement between primary tumors and paired metastatic lymph nodes were found in this study. The authors concluded that specimens from metastatic lesions and primary tumors are equally suitable for detection ALK rearrangement.

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Clinicopathologic characteristics of ALK rearrangements in primary lung adenocarcinoma with identified EGFR and KRAS status

Abstract: The ALK rearrangements are independently associated with younger age and the EGFR wild type. The EGFR mutations and the ALK rearrangements are rarely coexistent. The ALK rearrangements and the KRAS mutations are mutually exclusive.

Cited by 32 publications

References 28 publications

Mutational Profile and New IASLC/ATS/ERS Classification Provide Additional Prognostic Information about Lung Adenocarcinoma: A Study of 125 Patients from Brazil

Mutational Profile and New IASLC/ATS/ERS Classification Provide Additional Prognostic Information about Lung Adenocarcinoma: A Study of 125 Patients from Brazil

Association between the histological subtype of lung adenocarcinoma, EGFR/KRAS mutation status and the ALK rearrangement according to the novel IASLC/ATS/ERS classification

High concordance of ALK rearrangement between primary tumor and paired metastatic lymph node in patients with lung adenocarcinoma

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