Metaplastic breast carcinoma, a rare entity (<1% of breast neoplasms), lacks comprehensive spectroscopic characterization. This study aimed to address this gap by providing a qualitative and quantitative spectroscopic profile of metaplastic carcinoma in comparison to ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC).
Methods
A retrospective analysis was conducted on archival tissue blocks of metaplastic carcinoma (n = 10), DCIS (n = 12), and IDC (n = 31). Sections were stained with hematoxylin and eosin for histological confirmation. Attenuated total reflectance Fourier-transform infrared spectroscopy was performed on adjacent unstained sections, with normal breast tissue (n = 10) serving as the control. Spectral data were analyzed using t-tests to identify significant differences in peak intensities and ratios. Hierarchical clustering analysis and receiver operating characteristic curves were generated to assess the diagnostic potential of selected spectral features.
Results
Spectral analysis revealed that mean peak intensities were generally lower in all carcinoma subtypes compared to normal breast tissue. Specific ratios, including A1237/A1080 (phosphate; p < 0.01), A1043/1543 (glycogen; p < 0.01), and A1080/A1632 (nucleocytoplasmic index; p < 0.03), were significantly elevated in carcinomatous tissues. Receiver operating characteristic analysis identified peak 3,280 (area under the curve (AUC) = 0.93–0.96) as highly effective in differentiating normal from carcinomatous tissues. Peak 2,922 showed specificity for distinguishing normal tissue from IDC (AUC ≈ 0.7). Peak 1,744 effectively discriminated between DCIS and metaplastic carcinoma (AUC = 0.7). The ratio 1,080/1,632 (nucleocytoplasmic ratio) demonstrated exceptional diagnostic accuracy, distinguishing normal from carcinomatous tissues (AUC ≈ 1.0), DCIS from IDC (AUC ≈ 0.86), and DCIS from metaplastic carcinoma (AUC ≈ 0.8).
Conclusions
FTIR spectroscopy holds diagnostic promise, particularly for distinguishing metaplastic breast carcinoma from ductal carcinoma in situ and normal tissue. While statistically significant biomarkers are crucial for diagnostic integration, this study demonstrates that statistical significance does not guarantee diagnostic relevance. Protein peaks, particularly Amide A (3,280 cm−1), Amide I (1,632 cm−1), and β-sheet Amide II (1,543 and 1,535 cm−1), exhibit strong diagnostic potential based on ROC analysis. Notably, the 1,080/1,632 ratio, reflecting the nucleocytoplasmic ratio, demonstrates an accurate diagnostic model. Cluster analysis reveals synergistic peak interactions that highlight chemical relationships among protein (1,453 and 1,386 cm−1), lipid (1,446 and 1,394 cm−1), and amide peaks (1,632 and 3,280 cm−1). Cutoff point analysis quantitatively supports these findings, indicating similar biochemical signatures within clusters. The exceptional AUC of 1.0 for the nucleocytoplasmic ratio (A1080/A1632) underscores its clinical utility, aligning with conventional nucleocytoplasmic characterization in carcinoma diagnosis. These insights, while preliminary, advance understanding of the biochemical origins of metaplastic breast carcinoma and pave the way for refined diagnostic protocols and biomarker development. Further research is essential to validate and translate these findings into broader carcinoma research and clinical applications.
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https://www.xiahepublishing.com/2472-0712/ERHM-2025-00014
The study was recently published in the Exploratory Research and Hypothesis in Medicine .
Exploratory Research and Hypothesis in Medicine (ERHM) publishes original exploratory research articles and state-of-the-art reviews that focus on novel findings and the most recent scientific advances that support new hypotheses in medicine. The journal accepts a wide range of topics, including innovative diagnostic and therapeutic modalities as well as insightful theories related to the practice of medicine. The exploratory research published in ERHM does not necessarily need to be comprehensive and conclusive, but the study design must be solid, the methodologies must be reliable, the results must be true, and the hypothesis must be rational and justifiable with evidence.
