Next generation sequencing of lung adenocarcinoma subtypes with intestinal differentiation reveals distinct molecular signatures associated with histomorphology and therapeutic options

Jurmeister, Philipp; Vollbrecht, Claudia; Behnke, Anke; Frost, Nikolaj; Arnold, Alexander; Treue, Denise; Rückert, Jens-Carsten; Neudecker, Jens; Schweizer, Leonille; Klauschen, Frederick; Horst, David; Hummel, Michael; Dietel, Manfred; Laffert, Maximilian von

doi:10.1016/j.lungcan.2019.10.005

Cited by 24 publications

(23 citation statements)

References 32 publications

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“…On the other hand, both the frequent alteration of MMR and the high TMB reported in the literature, as well as the expression of immune checkpoint regulators, may suggest a potential sensitiveness of PAED to immunotherapy (Ref. 33), whose introduction in the clinical practice may significantly improve the outcome of such malignancies.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, Jurmeister et al confirmed for the first time the potential eligibility for treatment with immune checkpoint inhibitors in PAED patients, according to the validated presence of a high TMB but also of the membranous PD-L1 staining positivity in the tumour cells of PAED (Ref. 33). Furthermore, the same authors, based on the identification of the amplification of the RICTOR gene in PAED samples, suggested a potential therapeutic approach with mTORC1/2 inhibitors in these patients (Ref.…”

Section: Pathogenesis and Clinical Featuresmentioning

confidence: 95%

“…Furthermore, the same authors, based on the identification of the amplification of the RICTOR gene in PAED samples, suggested a potential therapeutic approach with mTORC1/2 inhibitors in these patients (Ref. 33).…”

Section: Pathogenesis and Clinical Featuresmentioning

confidence: 99%

“…Moreover, the finding in two samples of a RICTOR gene amplification induces the authors to hypothesise a potential therapeutic use of mTORC1/2 inhibitors in these patients (Ref. 33).…”

Section: Genomic Assessmentmentioning

confidence: 99%

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Pulmonary enteric adenocarcinoma: an overview

Palmirotta

Lovero

D’Oronzo

et al. 2020

Expert Rev. Mol. Med.

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Most commonly described as sporadic, pulmonary adenocarcinoma with enteric differentiation (PAED) is a rare variant of invasive lung cancer recently established and recognised by the World Health Organization. This tumour is highly heterogeneous and shares several morphological features with pulmonary and colorectal adenocarcinomas. Our objective is to summarise current research on PAED, focusing on its immunohistochemical and molecular features as potential tools for differential diagnosis from colorectal cancer, as well as prognosis definition and therapeutic choice. PAED exhibits an ‘entero-like’ pathological morphology in more than half cases, expressing at least one of the typical immunohistochemical markers of enteric differentiation, namely CDX2, CK20 or MUC2. For this reason, this malignancy appears often indistinguishable from a colorectal cancer metastasis, making the differential diagnosis laborious. Although standard diagnostic criteria have not been established yet, in the past few years, a number of approaches have been addressed, aimed at defining specific immunohistochemical and molecular signatures. Based on previously published literature, we have collected and analysed molecular and immunohistochemical data on this rare neoplasm, and have described the state of the art on diagnostic criteria as well as major clinical and therapeutic implications. The analysis of data from 295 patients from 58 published articles allowed us to identify the most represented immunohistochemical and molecular markers, as well as major differences between Asian PAEDs and those diagnosed in European/North American countries. The innovative molecular approaches, exploring driver mutations or new gene alterations, could help to identify rare prognostic factors and guide future tailored therapeutic approaches to this rare neoplasm.

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Section: Discussionmentioning

confidence: 99%

Section: Pathogenesis and Clinical Featuresmentioning

confidence: 95%

Section: Pathogenesis and Clinical Featuresmentioning

confidence: 99%

“…Moreover, the finding in two samples of a RICTOR gene amplification induces the authors to hypothesise a potential therapeutic use of mTORC1/2 inhibitors in these patients (Ref. 33).…”

Section: Genomic Assessmentmentioning

confidence: 99%

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Pulmonary enteric adenocarcinoma: an overview

Palmirotta

Lovero

D’Oronzo

et al. 2020

Expert Rev. Mol. Med.

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“…Recent research studies have proved that KRAS mutation was the most frequent oncogenic driver mutations in IMA (63–90%) followed by NRG1 fusions (7–27%) ( 8 – 11 ). Compared with non-mucinous adenocarcinoma (non-IMA), IMA has a lower rate of EGFR mutations (only 0–5%) and a higher rate of ALK rearrangements (2.2%) and ERBB2 mutations (1.2%) ( 6 , 12 , 13 ). In addition, rare gene mutations, such as HER2, BRAF, and PI3KA mutations, and rare gene fusions, such as TRIM4-BRAF, VAMP2-NRG1, and CD74-NRG1fusions, were observed in IMA patients with KRAS-negative ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Clinical Relevance of PD-L1 Expression and CD8+ T Cells’ Infiltration in Patients With Lung Invasive Mucinous Adenocarcinoma

Wang

et al. 2021

Front. Oncol.

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BackgroundInvasive mucinous adenocarcinoma (IMA) of the lung is a rare and distinct subtype of adenocarcinoma. At present, people have no idea whether IMA patients can benefit from immunotherapy and target therapy; thus there is an urgent need to clarify the immune microenvironment and genetic characteristics of this cohort.MethodsA total of 31 IMA patients matched with 27 non-mucinous adenocarcinoma (non-IMA) patients were enrolled in this study, and clinical data was collected. The expression of PD-L1, CD8+ tumor-infiltrating lymphocytes (TILs) and ALK was determined by immunohistochemistry. Polymerase Chain Reaction was used to determine the mutations of EGFR. The Chi-square test, Kaplan–Meier method and Cox proportional hazard regression model were used to explore the correlations between these clinicopathological variables, survival and identify risk factors.ResultsOf the patients with IMA 9.7% (3/31) revealed positive PD-L1 expression and 35.5% (11/31) showed CD8+ TIL infiltration, which were markedly lower than that of non-IMA group [PD-L1: 48.1% (13/27); CD8: 81.5% (22/27)]. Moreover, five (16.1%) patients in IMA group and 10 (37.0%) patients in non-IMA group had EGFR mutations, and nine (29.0%) patients in IMA group and zero (0.0%) patient in non-IMA group had ALK rearrangements. Additionally, we observed that IMA patients with CD8+ TIL infiltration had a worse prognosis than CD8-negative group (P = 0.024). Multivariate analyses showed that CD8 was an independent prognostic factor for patient’s survival (HR = 5.60, 95% CI: 1.35–23.22, P = 0.017).ConclusionPatients with IMA have down-regulated expression of PD-L1 and less CD8+ TIL infiltration in tumor microenvironment. Besides, a lower frequency of EGFR mutations was detected in patients with IMA than non-IMA patients while a higher rate of ALK rearrangements was found. Our results provide important reference for therapy of lung IMA.

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Case of lung fine needle aspiration showing mucinous cells and extracellular mucin

Saliba,

Smithgall,

Saqi

et al. 2024

Diagnostic Cytopathology

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Mucinous neoplasm with extracellular mucin can be challenging to interpret on fine needle aspiration and core biopsies. Determining the biologic origin of the mucin/mucinous cells, that is, benign/incidental versus neoplasm, invasive versus in situ, and primary versus metastatic tumors, requires a thorough multidisciplinary evaluation. The work up of these lesions includes morphologic analysis with ancillary immunohistochemical and/or molecular studies and correlation with clinical and imaging studies. This review outlines a practical approach to the diagnosis of mucinous lesions in the lung with comprehensive review of literature.

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Next generation sequencing of lung adenocarcinoma subtypes with intestinal differentiation reveals distinct molecular signatures associated with histomorphology and therapeutic options

Cited by 24 publications

References 32 publications

Pulmonary enteric adenocarcinoma: an overview

Pulmonary enteric adenocarcinoma: an overview

Clinical Relevance of PD-L1 Expression and CD8+ T Cells’ Infiltration in Patients With Lung Invasive Mucinous Adenocarcinoma

Case of lung fine needle aspiration showing mucinous cells and extracellular mucin

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