Abstract 97: A novel PTPRK-FILIP1 fusion gene in invasive mucinous adenocarcinoma of lung without known driver mutations

Genetic Alterations in Chinese Resected Lung Cancer with Invasive Mucinous Adenocarcinoma: Genomic Profiling and Prognostic Value Analysis

10.31219/osf.io/gb8ct ◽

2021 ◽

Author(s):

James D. Klingensmith

Keyword(s):

Mucinous Adenocarcinoma ◽

Pi3k Pathway ◽

Genetic Alterations ◽

Egfr Mutations ◽

Driver Mutations ◽

Genetic Profile ◽

Kras Mutations ◽

Genetic Characteristics ◽

Value Analysis ◽

Invasive Mucinous Adenocarcinoma

Lung invasive mucinous adenocarcinoma (IMA) is a unique histological subtype with different clinical and pathological characteristics. Despite prior genomic investigations on lung IMA, little is known about the genetic features and prognosis-related biomarkers in Chinese surgically resected lung IMA. IMA showed a distinct genetic profile, with more diversified driver mutations and co-occurrence of tumor drivers/suppressors than non-IMA. From non-IMA to mixed-IMA to pure-IMA, the frequency of EGFR (72.0 percent vs. 40.0 percent vs. 23.1 percent, p=0.002) and ALK (undetected vs. 20.0 percent vs. 26.9%, p=0.015) changes exhibited a trend of steady decline and rise, respectively. KRAS mutations were more common in pure-IMA than in mixed-IMA, however the difference was statistically insignificant (23.1 percent vs. 4.0 percent, p=0.10). Pure-IMA had a lower rate of TP53 mutation than mixed-IMA and non-IMA (23.1 percent vs. 52.0 percent vs. 56.0 percent, p=0.03). Furthermore, IMA had fewer arm-level amplifications (p=0.04) and more arm-level deletions (p=0.004) than non-IMA, with a steady drop in amplification and rise in deletion frequency from non-IMA to mixed-IMA to pure-IMA, respectively. Patients with EGFR mutations (mDFS=30.3 vs. 16.0 months, HR=0.19, P=0.027) and PI3K pathway mutations (mDFS=36.0 vs. 16.0 months, HR=0.12, P=0.023) had longer DFS than patients with poorly differentiated tumors (mDFS=14.1 vs. 28.0 months, HR=3.75, p=0.037) or KRAS mutations (mDFS=13 KRAS mutations, PI3K pathway changes, and tumor differentiation status were all shown to be independent predictors with statistically significant effects on IMA patients' clinical outcomes in multivariate analysis. Our research shed light on the genomics of Chinese lung IMA that had been surgically removed. In IMA patients with stage III illness, we also discovered many genetic characteristics that might be used as indicators for postoperative recurrence.

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Concomitant Presence of EGFR and ALK Fusion Gene Mutation in Adenocarcinoma of Lung: A Case Report and Review of the Literature

Journal of Pharmacy Practice ◽

10.1177/0897190017704751 ◽

2017 ◽

Vol 31 (2) ◽

pp. 244-248

Author(s):

Nishitha Thumallapally ◽

Hana Yu ◽

Mohammad Farhan ◽

Uroosa Ibrahim ◽

Maricel Odiami

Keyword(s):

Molecular Mechanisms ◽

Fusion Gene ◽

Growth Factor Receptor ◽

Egfr Mutations ◽

Driver Mutations ◽

Alk Rearrangement ◽

Anaplastic Lymphoma ◽

Adenocarcinoma Of Lung ◽

Practical Guidelines ◽

Oncogenic Driver

Empirical evidence has long suggested that oncogenic driver mutations in non-small-cell lung cancer are mutually independent. However, recent studies reported in pertinent literature reveal that concomitant epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangement can occur in a subset of patients with NSCLC. In order to shed further light on this issue, we report a case of adenocarcinoma of lung harboring both EGFR mutation in exon 21 (L861Q) and ALK rearrangement. This allows us to speculate on likely molecular mechanisms underlying this uncommon phenomenon, while also offering some practical guidelines on the therapeutic options that could benefit patients diagnosed with this dual-positive tumor.

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Clinicopathological Features and Survival Outcomes of Primary Pulmonary Invasive Mucinous Adenocarcinoma

Cancers ◽

10.3390/cancers13164103 ◽

2021 ◽

Vol 13 (16) ◽

pp. 4103

Author(s):

Chien-Hung Gow ◽

Min-Shu Hsieh ◽

Yi-Nan Liu ◽

Yi-Hsuan Lee ◽

Jin-Yuan Shih

Keyword(s):

Mucinous Adenocarcinoma ◽

Early Stage ◽

Clinicopathological Features ◽

Stage I ◽

Driver Mutations ◽

Survival Outcomes ◽

Grading System ◽

Low Grade ◽

High Grade ◽

Invasive Mucinous Adenocarcinoma

Pulmonary invasive mucinous adenocarcinoma (IMA) has unique histological patterns. This study aimed to comprehensively evaluate the clinicopathological features, prognosis, and survival outcomes of IMAs. We retrospectively identified 77 patients with pulmonary IMA and reviewed their clinical and pathological features. Another 520 patients with non-IMA-type ADC were retrieved for comparison with patients with IMA. A new two-tier grading system (high-grade and low-grade IMAs) modified from the pancreatic intraepithelial neoplasia classification system was used for survival analyses. Compared to patients with non-IMA-type ADC, patients with IMA tended to have never smoked (p = 0.01) and had early-stage IMA at initial diagnosis (p < 0.001). For stage I–II diseases, the five-year overall survival (OS) rates were 76% in IMAs and 50% in non-IMA-type ADCs, and a longer OS was observed in patients with IMA (p = 0.002). KRAS mutations were the most commonly detected driver mutations, which occurred in 12 of the 28 (43%) patients. High-grade IMAs were associated with a shorter recurrence-free survival (RFS) for stage I–IIIA diseases (p = 0.010) than low-grade IMAs but not for OS. In conclusion, patients with stage I and II IMA had better OS than those with non-IMA-type ADC. A new two-tier grading system might be useful for predicting RFS in stage I–IIIA IMAs.

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A case of bilateral invasive mucinous adenocarcinoma of the lung with severe productive cough and dyspnea successfully treated with palliative lung lobectomy

Respiratory Medicine Case Reports ◽

10.1016/j.rmcr.2021.101368 ◽

2021 ◽

Vol 32 ◽

pp. 101368

Author(s):

Takanori Horiguchi ◽

Shigehisa Yanagi ◽

Masaki Tomita ◽

Ryo Maeda ◽

Kazuko Uto ◽

...

Keyword(s):

Mucinous Adenocarcinoma ◽

Productive Cough ◽

Adenocarcinoma Of The Lung ◽

Lung Lobectomy ◽

Invasive Mucinous Adenocarcinoma

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Snowball‐like appearance on radial endobronchial ultrasonography in a patient with invasive mucinous adenocarcinoma

Respirology Case Reports ◽

10.1002/rcr2.735 ◽

2021 ◽

Vol 9 (4) ◽

Author(s):

Takeshi Kawaguchi ◽

Daisuke Himeji ◽

Kiichio Beppu ◽

Kousuke Marutsuka

Keyword(s):

Mucinous Adenocarcinoma ◽

Endobronchial Ultrasonography ◽

Invasive Mucinous Adenocarcinoma

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

Frontiers in Oncology ◽

10.3389/fonc.2021.683432 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xiaoling Xu ◽

Na Li ◽

Ding Wang ◽

Wei Chen ◽

Yun Fan

Keyword(s):

Mucinous Adenocarcinoma ◽

Target Therapy ◽

Tumor Infiltrating Lymphocytes ◽

Egfr Mutations ◽

Chi Square ◽

Genetic Characteristics ◽

Kaplan Meier ◽

Chi Square Test ◽

Cox Proportional Hazard Regression ◽

Invasive Mucinous Adenocarcinoma

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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