Abstract
Microcalcification is one of the most common radiological and pathological features of breast ductal carcinoma in situ (DCIS), and to a lesser extent, invasive ductal carcinoma. We evaluated messenger RNA (mRNA) transcriptional profiles associated with ectopic mammary mineralization. A total of 109 breast cancers were assayed with oligonucleotide microarrays. The associations of mRNA abundance with microcalcifications and relevant clinical features were evaluated. Microcalcifications were present in 86 (79%) patients by pathological examination, and 81 (94%) were with coexistent DCIS, while only 13 (57%) of 23 patients without microcalcification, the invasive diseases were accompanied with DCIS (χ2-test, P < 0.001). There were 69 genes with differential mRNA abundance between breast cancers with and without microcalcifications, and 11 were associated with high-grade (comedo) type DCIS. Enriched Gene Ontology categories included glycosaminoglycan and aminoglycan metabolic processes and protein ubiquitination, indicating an active secretory process. The intersection (18 genes) of microcalcificaion-associated and DCIS-associated genes provided the best predictive accuracy of 82% with Bayesian compound covariate predictor. Ten genes were further selected for prognostic index score construction, and five-year relapse free survival was 91% for low-risk and 83% for high-risk group (log-rank test, P = 0.10). Our study suggested that microcalcification is not only the earliest detectable radiological sign for mammography screening but the phenomenon itself may reflect the underling events during mammary carcinogenesis. Future studies to evaluate the prognostic significance of microcalcifications are warranted.
Highlights
Microcalcification is one of the most common radiological and pathological features of breast ductal carcinoma in situ (DCIS), and to a lesser extent, invasive ductal carcinoma
Since recent studies have suggested a connection between genes involved in osteoblast differentiation and breast carcinogenesis, we evaluated CXCR4, matrix metalloproteinases (MMP)-1, CTGF, FGF5, and IL11, all of which were suggested by Kang et al as being interrogated in breast cancer osteolytic metastasis through microarray profiling and Northern blot confirmation[24]
There remains an unsolved debate on whether mammographic microcalcification is a passive phenomenon resulted from degraded cell debris during mammary gland proliferation or is itself an active process intervening in breast carcinogenesis
Summary
Microcalcification is one of the most common radiological and pathological features of breast ductal carcinoma in situ (DCIS), and to a lesser extent, invasive ductal carcinoma. The associations of mRNA abundance with microcalcifications and relevant clinical features were evaluated. There were 69 genes with differential mRNA abundance between breast cancers with and without microcalcifications, and 11 were associated with high-grade (comedo) type DCIS. Experiences learnt from screening studies have established mammography as the only valid imaging modality for breast cancer early detection and subsequent mortality r eduction[3]. The major clinical significance of type I and II differentiation comes from the observation that type I microcalcification is accompanied with predominately benign lesions while associated lesions are half benign and half malignant for type II m icrocalcification[8]
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