ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Rb Tumor Suppressor in Small Cell Lung Cancer: Combined Genomic and IHC Analysis with a Description of a Distinct Rb-Proficient Subset.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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52 citing papers in PubMed, 84 citations in OpenAlex.
- Molecular classification and biomarkers of outcome with immunotherapy in extensive-stage small-cell lung cancer: analyses of the CASPIAN phase 3 study.Molecular cancer · 2024Trial
- Sintilimab with two cycles of chemotherapy for the treatment of advanced squamous non-small cell lung cancer: a phase 2 clinical trial.Nature communications · 2024Trial
- High-risk human papillomavirus infection and immunohistochemical expression patterns of p16 and Rb in primary and metastatic squamous cell carcinoma of the lung.Virchows Archiv : an international journal of pathology · 2026Article
- Integrating molecular subtypes, genomics and functional dependencies to identify context-specific therapeutic vulnerabilities in small cell lung cancer.Biomarker research · 2026Review
- Review
- Rewiring the Molecular Interplay of CDK4/6 Inhibitors in Lung Cancer: From Cell Cycle Control to Immune Microenvironment Remodeling.International journal of molecular sciences · 2026Review
- Genetic Medicine Approaches for Tumor Suppressor Loss: Therapeutic Replacement with Self-Amplifying RNA.Pharmaceutical research · 2026Review
- Transcriptional evidence of neuroendocrine cell plasticity beyond histological boundaries in lung neuroendocrine neoplasms: an in-silico analysis suggesting a progression model.Journal of experimental & clinical cancer research : CR · 2026Article
- Clinically actionable molecular alterations in Rb-retained small cell lung carcinoma variants.Virchows Archiv : an international journal of pathology · 2026Article
- Utility of RB1 immunohistochemistry for prognostic subtyping of pulmonary large cell neuroendocrine carcinoma.Virchows Archiv : an international journal of pathology · 2026Article
- Homologous recombination deficiency and hemizygosity drive resistance in breast cancer.Nature · 2026Article
- Rb expression in metastatic ER-positive breast cancer: implications for precision oncology.Breast cancer research and treatment · 2026Article
- Authentic neuroendocrine transdifferentiation from lung adenocarcinoma to small-cell lung cancer: a case report.BMC pulmonary medicine · 2026Article
- Potential Immune Microenvironment Biomarkers in SCLC: J-TAIL-2 Observational Study.JTO clinical and research reports · 2026Article
- Multiomic characterization of small cell lung cancer: Real-world insights into therapeutic opportunities.Cancer · 2026Article
- [Diagnostics of lung diseases based on small specimens : Biopsies and cytology].Pathologie (Heidelberg, Germany) · 2026Review
- Targeting Aurora A Kinase Enhance the CDK4/6 Inhibitor Sensitivity in HR+/HER2- Breast Cancer.Oncology research · 2026Article
- Case Report: Neuroendocrine-low POU2F3-positive small cell lung cancer presenting as a diagnostically unstable thoracic malignancy.Frontiers in oncology · 2026Article
- Concept of neuroendocrine neoplasms of all organs with a focus on grading, subtyping.Virchows Archiv : an international journal of pathology · 2026Review
- Extracellular matrix regulates lineage plasticity in prostate cancer through YAP/TEAD.bioRxiv : the preprint server for biology · 2025Article
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Abstract
purposeRB1 mutations and loss of retinoblastoma (Rb) expression represent consistent but not entirely invariable hallmarks of small cell lung cancer (SCLC). The prevalence and characteristics of SCLC retaining wild-type Rb are not well-established. Furthermore, the performance of targeted next-generation sequencing (NGS) versus immunohistochemistry for Rb assessment is not well-defined. EXPERIMENTAL
designA total of 208 clinical SCLC samples were analyzed by comprehensive targeted NGS, covering all exons of RB1, and Rb IHC. On the basis of established coordination of Rb/p16/cyclinD1 expression, p16-high/cyclinD1-low profile was used as a marker of constitutive Rb deficiency.
resultsFourteen of 208 (6%) SCLC expressed wild-type Rb, accompanied by a unique p16-low/cyclinD1-high profile supporting Rb proficiency. Rb-proficient SCLC was associated with neuroendocrine-low phenotype, combined SCLC with non-SCLC (NSCLC) histology and aggressive behavior. These tumors exclusively harbored CCND1 amplification (29%), and were markedly enriched in CDKN2A mutations (50%) and NSCLC-type alterations (KEAP1, STK11, FGFR1). The remaining 194 of 208 SCLC were Rb-deficient (p16-high/cyclinD1-low), including 184 cases with Rb loss (of which 29% lacked detectable RB1 alterations by clinical NGS pipeline), and 10 cases with mutated but expressed Rb.
conclusionsThis is the largest study to date to concurrently analyze Rb by NGS and IHC in SCLC, identifying a 6% rate of Rb proficiency. Pathologic-genomic data implicate NSCLC-related progenitors as a putative source of Rb-proficient SCLC. Consistent upstream Rb inactivation via CDKN2A/p16↓ and CCND1/cyclinD1↑ suggests the potential utility of CDK4/6 inhibitors in this aggressive SCLC subset. The study also clarifies technical aspects of Rb status determination in clinical practice, highlighting the limitations of exon-only sequencing for RB1 interrogation. See related commentary by Mahadevan and Sholl, p. 4603.
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