Molecular and Histological Changes in Post-Treatment Biopsies of Non-Squamous Non-Small Cell Lung Cancer: A Retrospective Study

Vatrano, Simona; Righi, Luisella; Vavalà, Tiziana; Rapa, Ida; Busso, Marco; Izzo, Stefania; Cappia, Susanna; Veltri, Andrea; Papotti, Mauro; Scagliotti, Giorgio Vittorio; Novello, Silvia

doi:10.1007/s11523-015-0383-8

Cited by 10 publications

(11 citation statements)

References 32 publications

(38 reference statements)

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“…However, we hypothesized that a higher but still unknown percentage of advanced non‐operable LC cases were histologically heterogeneous, consisting of NSCLC associated with an SCLC component, in comparison with surgically resected cancers where the rate of major histologic heterogeneity is only 4% for NSCLC and 9–26% for SCLC. If the hypothesis is correct, the therapeutic strategy should be able to target one of the components, leading to the selective growth of the other . Again, in the well‐known setting of oncogenic‐driven LC, several cases of mixed EGFR ‐mutated NSCLC/SCLC have been reported, suggesting a degree of plasticity between the two histotypes in some cases, without the selective pressure of TKIs.…”

Section: Discussionmentioning

confidence: 99%

“…Usually, TKI resistance develops after an initial benefit through a variety of mechanisms. Among these, tumor histology changes are a mechanism of acquired resistance in EGFR‐mutated and ALK‐rearranged NSCLC cases . The availability of therapeutic approaches to overcome TKI resistance in oncogenic‐driven lung cancers (LCs) justifies secondary tumor biopsy in these patients …”

Section: Introductionmentioning

confidence: 99%

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Secondary biopsy of non‐oncogenic‐driven lung cancer may reveal a clinically sensible histologic change. A brief report of two paradigmatic cases

et al. 2017

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After an initial benefit, non‐small‐cell lung cancer (NSCLC) patients receiving therapy with tyrosine kinase inhibitors develop drug resistance through a variety of mechanisms. Among these, tumor histology changes are a mechanism of acquired resistance in epidermal growth factor receptor‐mutated and anaplastic lymphoma kinase‐rearranged NSCLC cases. The current availability of therapeutic approaches to overcome tyrosine kinase inhibitor resistance in oncogenic‐driven lung cancers justifies secondary tumor biopsy in these patients. On the other hand, little is known about the mechanism of disease progression in non‐oncogenic driven NSCLC. Nevertheless, NSCLC lacking “druggable” genetic alterations are not considered for secondary biopsy, as it is commonly believed that these tumors cannot develop histologic or molecular changes. Herein, we report two paradigmatic cases of wild‐type NSCLC showing histologic “change” on secondary biopsy, allowing for a successful switch in therapeutic strategy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Secondary biopsy of non‐oncogenic‐driven lung cancer may reveal a clinically sensible histologic change. A brief report of two paradigmatic cases

et al. 2017

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“…Genomic DNA was obtained from formalin-fixed paraffinembedded tissues after manual microdissection, for neoplastic cell enrichment (at least 50% of tumor cells), as previously reported [15]. Targeted next-generation sequencing analyses were performed in all samples using the Ion Torrent Personal Genome Machine (PGM, ThermoFisher Scientific), and an AmpliSeq custom panel targeting the entire coding sequence of 15 genes previously reported as adrenocortical carcinoma related: TP53, MSH2, MSH6, MLH1, PMS2, ATRX, DAXX, CTNNB1, MED12, MEN1, CTNNB1, PTCH1, APC, PTEN, ZNRF3.…”

Section: Dna Isolation and Mutational Analysismentioning

confidence: 99%

Detailed genomic characterization identifies high heterogeneity and histotype-specific genomic profiles in adrenocortical carcinomas

et al. 2018

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Molecular characterization of adrenocortical carcinoma has been recently established, but the correlation between molecular profiles and clinical and pathological characteristics is still poorly defined with no data available about genetic heterogeneity along disease progression. In this scenario, a detailed molecular profile was correlated with clinical and pathological characteristics in adrenocortical carcinoma patients to identify potentially novel biomarkers. Targeted next-generation sequencing and copy number variation analyses for 18 most frequently altered genes in adrenocortical carcinoma were assessed on 62 adult cases (including 10 with matched primary and metastatic/recurrence samples) and results correlated with major clinical and pathological characteristics of tumors. A total of 433 somatic deleterious genetic alterations (328 gene mutations and 105 copy number variations) were identified in 57/62 cases, five resulted wild type for all genes tested. TERT, CDK4, ZNRF3,and RB1 were altered in more than 30% of cases. Among histological variants genotypes were significantly different. Lowest mutation burden was found in the oncocytic type (p = 0.006), whereas the highest with a prevalence of RB1 (p = 0.001) and CDK4 (p = 0.002) was found in the conventional and myxoid ones, respectively. None of the 10 cases with matched samples showed a stable genotype along tumor progression, although allelic frequencies or percentages of altered nuclei at fluorescence in situ hybridization were in most cases similar among different tumor samples for genes that were stable along tumor progression. Among individual genes, an altered p53/Rb1 pathway was the strongest adverse molecular signature, being associated with high Ki-67 index, high tumor stage, aggressive disease status, and shorter disease-free survival. The genomic signature in adrenocortical carcinoma is changing along tumor progression and is associated with specific clinical and pathological features, including histological variant and prognosis.

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“…However, after a honeymoon period of response to therapy, acquired resistances can occur (21). The vast majority of cancers treated with target therapy harbor therapy-induced new genetic changes, in term of both acquisition and loss of gene alterations (22,23). Moreover, histological shift from well differentiated to poorly differentiated small cell cancer has been described as acquired resistance mechanism (23)(24)(25).…”

Section: Molecular Testingmentioning

confidence: 99%

“…The vast majority of cancers treated with target therapy harbor therapy-induced new genetic changes, in term of both acquisition and loss of gene alterations (22,23). Moreover, histological shift from well differentiated to poorly differentiated small cell cancer has been described as acquired resistance mechanism (23)(24)(25). Comprehensive molecular profiling of other more frequent lung cancer types including squamous and large cell carcinoma revealed a marked genomic complexity with less druggable alterations for the first and genetic features typical of other better differentiated carcinomas for the latter (26,27).…”

Section: Molecular Testingmentioning

confidence: 99%

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA)—from morphology to molecular testing

Righi¹,

Franzi²,

Montarolo³

et al. 2017

J. Thorac. Dis.

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In recent years, endobronchial ultrasound-guided TBNA (EBUS-TBNA) has emerged as an innovative technique for diagnosis and staging of lung cancer and has been successfully introduced into daily clinical practice with several advantages including minimally invasive approach, safe, cost-effective, real time image guidance, broad sampling capability, and rapid on-site evaluation (ROSE). Both cytological and histological approach could be useful to have material for diagnosis, immunohistochemical and molecular analyses which may be very important for targeted therapy with successful rate ranging from 89% to 98%. The utility of ROSE during EBUS-TBNA has been matter of debate. Indeed, although some evidence concluded that ROSE does not increase the diagnostic efficacy of EBUS-TBNA, other demonstrated that it improves the diagnostic yield of the procedure up to 30%, allows to avoid repetition of additional diagnostic procedures and reduces risk of complications. Furthermore the sample preparation by cytopathologist is optimized with the aid of direct macroscopic inspection, optimal smearing techniques, and triage of the sample permitting to obtain adequate tissue for diagnosis, ancillary techniques and molecular testing, when needed. Some pathological issues on EBUS-TBNA are reviewed and discussed with particular focus on ROSE and molecular testing.

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Molecular and Histological Changes in Post-Treatment Biopsies of Non-Squamous Non-Small Cell Lung Cancer: A Retrospective Study

Abstract: Background: Recently, in advanced non-small cell lung cancer (NSCLC), standard chemotherapy

Cited by 10 publications

References 32 publications

Secondary biopsy of non‐oncogenic‐driven lung cancer may reveal a clinically sensible histologic change. A brief report of two paradigmatic cases

Secondary biopsy of non‐oncogenic‐driven lung cancer may reveal a clinically sensible histologic change. A brief report of two paradigmatic cases

Detailed genomic characterization identifies high heterogeneity and histotype-specific genomic profiles in adrenocortical carcinomas

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA)—from morphology to molecular testing

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