Novel Immunohistochemical Profiling of Small-Cell Lung Cancer: Correlations Between Tumor Subtypes and Immune Microenvironment
Bibliographic record
Abstract
Background/Objectives: Small-cell lung cancer (SCLC) is a highly aggressive malignancy with an emerging molecular classification based on the expression of the transcription factors ASCL1, NEUROD1, and POU2F3. This study aimed to explore the relationship between these novel subtypes and the tumor immune microenvironment (TIME), particularly CD8+ and CD4+ tumor-infiltrating lymphocytes (TILs). Methods: In 51 cases of patients with SCLC, immunohistochemical (IHC) stains for ASCL1, NEUROD1, POU2F3, CD56, Ki67, CD8, and CD4 were performed. H-scores for the novel transcription factors were calculated to determine tumor subtype. CD8+ and CD4+ TIL counts were averaged across 10 high-power fields. The Kruskal–Wallis test and subsequent post hoc Dunn tests were used to determine the differences in transcription factor expression and TILs across subtypes. Results: In our cohort, 68.62% of our cases were SCLC-A, 9.80% were SCLC-N, 7.84% were SCLC-P, and 13.72% were SCLC-I. Significant differences were observed in the expression of ASCL1, NEUROD1, and POU2F3 across subtypes. CD8+ TILs were more abundant in SCLC-P and SCLC-I. CD8+ TILs were negatively correlated with ASCL1 expression (p < 0.05) and positively correlated with POU2F3 expression (p < 0.005). Conclusions: This study highlights the need to integrate the novel SCLC classification with data regarding the TIME to better inform patient prognosis and treatment.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".