Angelos Koutras | PubMed Health

PubMed2026

Intratumoral collagen correlates with histological grade and patient prognosis in breast cancer.

Histological grading, using the Nottingham Grading System (NGS), is a major prognostic indicator for breast cancer. NGS involves the scoring of cancer cell-related morphological features, yet it overlooks tumor microenvironment (TME) components such as collagen. Collagen proteins, integral to the extracellular matrix (ECM), influence tumor architecture and progression but their relationship with histological grade is not fully characterized. Here, we assessed intratumoral collagen deposition using Masson Trichrome staining of whole slides (n = 166), proteomic profiling (n = 2) and transcriptomic analyses of the METABRIC (n = 1827) and TCGA-BRCA (n = 753) cohorts. We showed that low-grade tumors display significantly higher intratumoral collagen deposition compared to high-grade tumors. Moreover, we demonstrated that collagen expression at the transcript and protein levels (Masson Trichrome) could discriminate Grade II carcinomas into distinct prognostic groups, in which patients with Grade II carcinomas with elevated levels of collagen expression were associated with lower pTNM stage and better survival outcomes. Our results support the inclusion of TME features, such as collagen deposition, to enhance prognostic accuracy in breast cancer.

Humans↗

PubMed2026

Tumor Mutational Landscape and Its Correlation With Histopathological Characteristics in Breast Cancer.

BACKGROUND/AIM: In breast cancer, knowledge of the associations between clinicopathologic characteristics, genetic changes, and subtype-specific patterns is expanding. This study investigated how pathological and clinical variables affect the actionability of Next Generation Sequencing (NGS)-based tumor molecular data. MATERIALS AND METHODS: 227 breast cancer patients referred to Genekor's laboratory for tumor molecular profile analysis were included in the study. Pathology records were used to assess critical clinicopathological features, including HER2, ER, PR, Ki67, grade, metastatic site, and age. A 1021-gene NGS-based multigene panel was utilized to assess tumor biology alongside tumor mutational burden (TMB) and microsatellite instability (MSI). RESULTS: Comprehensive genomic profiling revealed that 95.6% of the patients harbored at least one oncogenic or likely oncogenic alteration, highlighting the high diagnostic yield of NGS-based testing. Distinct subtype-specific patterns were observed: HR+/HER2- tumors were enriched for PIK3CA and ESR1 gene alterations, whereas triple-negative breast cancer (TNBC) was dominated by TP53 alterations. Clinically actionable alterations were most common in HR+/HER2- tumors (~60% on-label), whereas TNBC more often harbored off-label or trial-associated targets. The inclusion of tumor-agnostic biomarkers (TMB/MSI) increased on-label actionability up to 64.5% in HR+/HER2- tumors, primarily driven by TMB-high cases. Median TMB values were low, and age was the only independent predictor. Furthermore, the presence of actionable alterations was significantly higher in metastatic tumors, and TP53 alterations were associated with aggressive tumor characteristics. CONCLUSION: Comprehensive NGS-based genomic profiling identifies clinically actionable alterations in over half of breast cancer patients, with substantial variability across molecular subtypes. The HR+/HER2- subtype demonstrates the highest prevalence of on-label actionable biomarkers. These findings support the routine implementation of comprehensive genomic profiling, especially in metastatic HER2-negative breast cancer, to guide precision oncology strategies and enable enrollment in biomarker-driven clinical trials.

Humans↗