Lymphovascular invasion in breast cancer is associated with gene expression signatures of cell proliferation but not lymphangiogenesis or immune response.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32285241", "kind": "science-record", "revision": 4, "content_hash": "sha256:482424a996d62753effaec5e96a084e38ca40cb848434cda93e356a6f0144196", "created_at": "2026-11-01T17:33:32Z", "updated_at": "2026-11-01T22:44:44Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Lymphovascular invasion in breast cancer is associated with gene expression signatures of cell proliferation but not lymphangiogenesis or immune response.", "doi": "10.1007/s10549-020-05630-5", "pmid": "32285241", "authors": ["Mariko Asaoka", "Santosh K Patnaik", "Frank Zhang", "Takashi Ishikawa", "Kazuaki Takabe"], "journal": "Breast cancer research and treatment", "year": 2020, "abstract": "BACKGROUND: While the prognostic relevance of lymphovascular invasion (LVI) in breast cancer is well known, its molecular biology is poorly understood. We hypothesized that pathologically determined LVI reflects molecular features of tumors and can be discerned from their genomic and transcriptomic profiles.\nMETHODS: LVI status and Nottingham histological scores of primary breast tumors of The Cancer Genome Atlas (TCGA) project were assessed from pathology reports; other clinical and molecular data were obtained from TCGA data portals and publications. Two independent datasets (GSE5460 and GSE7849) were combined and used for validation.\nRESULTS: LVI status was determinable for 639 and 196 cases of the TCGA and validation cohorts, among whom LVI incidence was 37.8% and 37.2%, respectively. LVI was associated with high tumor Ki67 expression, advanced pathologic stage, and high Nottingham scores. LVI-positive cases had worse overall and progression-free survival regardless of cancer subtype. Surprisingly, in both cohorts, LVI was not associated with lymphangiogenesis or lymphatic vessel density as estimated from tumor expression of lymphatic endothelium-associated genes. LVI-positive tumors had higher genome copy number aberrations, aneuploidy, and homologous recombination defects, but not single-nucleotide variations or intra-tumor genome heterogeneity. Tumor immune cell composition and cytolytic activity was not associated with LVI status. On the other hand, expression of cell proliferation-related genes was significantly increased in LVI-positive tumors.\nCONCLUSION: Our study suggests that breast cancer with LVI is a highly proliferative cancer, and it does not correlate with gene expression markers for lymphangiogenesis or immune response.", "claims": [{"id": "claim-method", "statement": "For survival analyses, performed with survival (2.44) and greyzoneSurv (1.0) packages in R, Cox proportional hazard model and Kaplan-Meier method with log-rank test were used.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32285241", "locator": "sections[8] \"Statistical analyses\" paragraph 2", "quote": "For survival analyses, performed with survival (2.44) and greyzoneSurv (1.0) packages in R, Cox proportional hazard model and Kaplan-Meier method with log-rank test were used."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The GEO datasets used in this study are available at https://www.ncbi.nlm.nih.gov/geo with accession numbers GSE5460 and GSE7849. Clinical, gene-level mapped read counts of RNA sequencing data, and MAF files of TCGA-BRCA cases are available at Genome Data Commons portal of National Cancer Institute, USA at https://gdc.cancer.gov. Information on Nottingham scores and LVI status that was collated from pathology reports of the TCGA cases is in Table S2. Other data used in this study is available from sources cited in the Materials and Methods section.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32285241", "locator": "sections[19] \"fn-group\" paragraph 1", "quote": "The GEO datasets used in this study are available at https://www.ncbi.nlm.nih.gov/geo with accession numbers GSE5460 and GSE7849. Clinical, gene-level mapped read counts of RNA sequencing data, and MAF files of TCGA-BRCA cases are available at Genome Data Commons portal of National Cancer Institute, USA at https://gdc.cancer.gov. Information on Nottingham scores and LVI status that was collated from pathology reports of the TCGA cases is in Table S2. Other data used in this study is available from sources cited in the Materials and Methods section."}], "state": "complete"}, {"id": "claim-target-result", "statement": "TCGA patients with LVI-positive tumors had shorter progression-free interval and worse overall survival.", "kind": "quantitative", "target": {"value": 3.2, "unit": "hazard ratio", "tolerance": null, "source": "TCGA patients with LVI-positive tumors had shorter progression-free interval (p = 0.044, hazard ratio [HR] = 2.3), as well as worse overall survival (OS; p = 0.002, HR = 3.2; Fig. 1a)."}, "evidence": [{"asset": "source:pmid:32285241", "locator": "sections[10] \"LVI associates with worse survival in both TCGA and validation cohorts\" paragraph 2", "quote": "TCGA patients with LVI-positive tumors had shorter progression-free interval (p = 0.044, hazard ratio [HR] = 2.3), as well as worse overall survival (OS; p = 0.002, HR = 3.2; Fig. 1a)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "TCGA patients with LVI-positive tumors had shorter progression-free interval and worse overall survival.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:32285241"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32285241", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1007/s10549-020-05630-5", "sha256": "sha256:296e9d4f68ef5dfa729be4b35b0fb5891a836cb366c0a3a5cd0cdb927eab1ee5", "bytes": 31381, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1007/s10549-020-05630-5", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7269116", "source": "ncbi_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}], "gaps": []}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "For survival analyses, performed with survival (2.44) and greyzoneSurv (1.0) packages in R, Cox proportional hazard model and Kaplan-Meier method with log-rank test were used."}}, {"id": "method-2", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "log-rank"}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "logrank_test", "expected_value": 3.2, "unit": "hazard ratio", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["survival_km"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R4", "reachable": false, "accessions": ["GSE5460 and GSE7849"], "resolved_accessions": [], "statements": ["The GEO datasets used in this study are available at https://www.ncbi.nlm.nih.gov/geo with accession numbers GSE5460 and GSE7849. Clinical, gene-level mapped read counts of RNA sequencing data, and MAF files of TCGA-BRCA cases are available at Genome Data Commons portal of National Cancer Institute, USA at https://gdc.cancer.gov. Information on Nottingham scores and LVI status that was collated from pathology reports of the TCGA cases is in Table S2. Other data used in this study is available from sources cited in the Materials and Methods section."], "basis": "The paper names GSE5460 and GSE7849, but the accession does not resolve in the repository (no reason recorded), so the data cannot be reached from here. 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