Gal Sahar, Pavan Mariela J, Vidavsky Netta
Department of Chemical Engineering, Ben-Gurion University of the Negev Beer-Sheva 8410501 Israel
Ilse Katz Institute for Nanoscale Science & Technology, Ben-Gurion University of the Negev Beer-Sheva 8410501 Israel.
RSC Adv. 2024 Sep 10;14(39):28741-28752. doi: 10.1039/d4ra04137b. eCollection 2024 Sep 4.
Pathological crystallization within soft tissues often yields biominerals with properties differing from those of their geological or synthetic counterparts. Microcalcifications (MCs) are abundant in breast tumors, particularly in non-invasive lesions, such as ductal carcinoma (DCIS). Given the challenge of predicting DCIS progression into invasive cancer, it has been suggested that MCs can be leveraged to inform DCIS prognosis. The predominant type of breast MCs are those containing calcium phosphates (CaP), whose crystal properties are commonly held to correlate with malignancy. Less common are non-CaP minerals, which have received less attention, as they are associated mainly with benign lesions. Here, we conducted a retrospective study of tissue samples collected from patients who were originally diagnosed with DCIS and whose current medical status is known. We examined the elemental composition, morphology, and crystal phases of 398 MCs, aiming to investigate potential correlations between MC crystal properties and the progression of DCIS. Our findings revealed primarily non-CaP MCs, an observation that was likely made possible only by the tissue processing methodology employed, which did not involve harsh conditions. We found that non-CaP MCs were abundant in DCIS lesions, that they exhibited diverse morphologies and sizes, and that they were composed of calcite and dolomite. Dolomite formation in cancer has not been reported previously and may be linked to pH fluctuations in the tumor microenvironment. The small size of DCIS lesions often requires pathologists to use the entire sample, thus reducing the number of samples available for further research. Nonetheless, despite our limited sample size, the observed trend indicated an association of dolomite MCs with DCIS lesions that progressed into invasive cancer over time.
软组织内的病理性结晶通常会产生性质不同于其地质或合成对应物的生物矿物。微钙化(MCs)在乳腺肿瘤中很常见,尤其是在非侵袭性病变中,如导管原位癌(DCIS)。鉴于预测DCIS进展为浸润性癌存在挑战,有人提出可以利用MCs来判断DCIS的预后。乳腺MCs的主要类型是含磷酸钙(CaP)的,其晶体特性通常被认为与恶性程度相关。不太常见的是非CaP矿物,由于它们主要与良性病变相关,因此受到的关注较少。在此,我们对最初被诊断为DCIS且目前已知医疗状况的患者所采集的组织样本进行了一项回顾性研究。我们检查了398个MCs的元素组成、形态和晶相,旨在研究MC晶体特性与DCIS进展之间的潜在相关性。我们的研究结果主要揭示了非CaP MCs,这一观察结果可能仅通过所采用的组织处理方法才得以实现,该方法不涉及苛刻条件。我们发现非CaP MCs在DCIS病变中很丰富,它们呈现出多样的形态和大小,并且由方解石和白云石组成。癌症中白云石的形成此前未见报道,可能与肿瘤微环境中的pH波动有关。DCIS病变体积小,病理学家通常需要使用整个样本,从而减少了可用于进一步研究的样本数量。尽管如此,尽管我们的样本量有限,但观察到的趋势表明白云石MCs与随时间进展为浸润性癌的DCIS病变有关。