Differential molecular markers of primary lung tumors and metastatic sites indicate different possible treatment selections in patients with metastatic lung adenocarcinoma

Deng, Lili; Deng, Hong-Bin; Lu, Changlian; Gao, Ge; Wang, F.; Yu, Yang

doi:10.1007/s12094-018-1906-4

Cited by 2 publications

(3 citation statements)

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“…In both breast and lung carcinomas, the expression of prognostic markers in metastatic lesions is known to differ from the primary tumor in numerous cases. 12,26 In cases where IHC would not have provided additional clinically relevant information, dual commitments to cost containment and quick turn-around time might have influenced the pathologists' decision to forgo IHC testing. 25 IHC was performed in 39 of the 42 cases in which the primary tumor site was not known; it helped to identify the primary tumor site in 19 cases and rendered a diagnosis of neuroendocrine tumor in an additional 3 cases.…”

Section: Discussionmentioning

confidence: 99%

“…10,11 Similarly, liver metastasis affect survival in patients with gastrointestinal stromal tumor; the 5 years overall survival for those with and without liver metastasis was reported to be 39.9% and 75.5%, respectively. 12 The vast majority of patients with gastrointestinal stromal tumors have only liver metastasis. Because long term complete remissions are rare with imatinib alone, the current standard of care combines imatinib with complete surgical resection.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Metastatic Liver Tumors in Surgical Pathology: Impact of Contemporary Diagnostic and Therapeutic Paradigms in a Tertiary Care Center

2021

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We analyzed metastatic liver tumors received in the department of pathology in a tertiary care center over a 3-year period. There were 509 metastatic liver tumors; counterintuitively, there were as many resections (235 cases) as biopsies (274 cases). This unexpected finding reflects contemporaneous organ-specific paradigms for diagnosis and management of metastatic liver disease in oncologic practice, and the association of our practice with a National Cancer Institute-designated comprehensive cancer center with expertise and specialization in liver surgery. We receive a large number of resections for metastatic liver tumors because metastasectomy from a variety of primary tumors is associated with improved overall, and in many instances, disease-free, long-term survival. Metastatic colorectal carcinomas, metastatic neuroendocrine tumors, and metastatic gastrointestinal stromal tumors constituted 78% of resections because the largest body of literature and cumulative experience exists for these lesions. In contrast, breast carcinomas and pancreatic carcinomas, which are the next common metastatic liver tumors were biopsied but rarely resected, because metastasectomy is not the standard of care for these tumors. Immunohistochemistry was performed in less than a quarter of the total number of cases (23%), because the primary tumor site was known in the vast majority of cases. Of the 42 cases with unknown primary tumor, it was elucidated in 50% of the cases by immunohistochemical and clinical work-up. Of the cases with known primary tumor, immunohistochemistry was performed mostly in metastatic breast, colon, and lung carcinomas. In these cases, biomarker analyses provided additional information relevant to clinical management.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Metastatic Liver Tumors in Surgical Pathology: Impact of Contemporary Diagnostic and Therapeutic Paradigms in a Tertiary Care Center

2021

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Identification of 5-Gene Signature Improves Lung Adenocarcinoma Prognostic Stratification Based on Differential Expression Invasion Genes of Molecular Subtypes

Zheng¹,

Deng²,

Yang

2020

BioMed Research International

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Background. The acquisition of invasive tumor cell behavior is considered to be the cornerstone of the metastasis cascade. Thus, genetic markers associated with invasiveness can be stratified according to patient prognosis. In this study, we aimed to identify an invasive genetic trait and study its biological relevance in lung adenocarcinoma. Methods. 250 TCGA patients with lung adenocarcinoma were used as the training set, and the remaining 250 TCGA patients, 500 ALL TCGA patients, 226 patients with GSE31210, 83 patients with GSE30219, and 127 patients with GSE50081 were used as the verification data sets. Subtype classification of all TCGA lung adenocarcinoma samples was based on invasion-associated genes using the R package ConsensusClusterPlus. Kaplan-Meier curves, LASSO (least absolute contraction and selection operator) method, and univariate and multivariate Cox analysis were used to develop a molecular model for predicting survival. Results. As a consequence, two molecular subtypes for LUAD were first identified from all TCGA all data sets which were significant on survival time. C1 subtype with poor prognosis has higher clinical characteristics of malignancy, higher mutation frequency of KRAS and TP53, and a lower expression of immune regulatory molecules. 2463 differentially expressed invasion genes between C1 and C2 subtypes were obtained, including 580 upregulation genes and 1883 downregulation genes. Functional enrichment analysis found that upregulated genes were associated with the development of tumor pathways, while downregulated genes were more associated with immunity. Furthermore, 5-invasion gene signature was constructed based on 2463 genes, which was validated in four data sets. This signature divided patients into high-risk and low-risk groups, and the LUDA survival rate of the high-risk group is significantly lower than that of the low-risk group. Multivariate Cox analysis revealed that this gene signature was an independent prognostic factor for LUDA. Compared with other existing models, our model has a higher AUC. Conclusion. In this study, two subtypes were identified. In addition, we developed a 5-gene signature prognostic risk model, which has a good AUC in the training set and independent validation set and is a model with independent clinical characteristics. Therefore, we recommend using this classifier as a molecular diagnostic test to assess the prognostic risk of patients with LUDA.

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Differential molecular markers of primary lung tumors and metastatic sites indicate different possible treatment selections in patients with metastatic lung adenocarcinoma

Cited by 2 publications

References 35 publications

Metastatic Liver Tumors in Surgical Pathology: Impact of Contemporary Diagnostic and Therapeutic Paradigms in a Tertiary Care Center

Metastatic Liver Tumors in Surgical Pathology: Impact of Contemporary Diagnostic and Therapeutic Paradigms in a Tertiary Care Center

Identification of 5-Gene Signature Improves Lung Adenocarcinoma Prognostic Stratification Based on Differential Expression Invasion Genes of Molecular Subtypes

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