Quantification of stromal reaction in breast carcinoma and its correlation with tumor grade and free progression survival

Cancer progression results from a complex interplay between tumor cells and the extracellular milieu. In breast carcinoma, the stromal microenvironment has been suggested to play a major role in promoting tumor growth, progression, and invasion. The stroma of 154 resected specimens of invasive breast carcinoma of no special type was quantified using a digital image analyzer. Statistical analyses were performed between the quantity of stroma and survival, as well as between progression-free survival and clinicopathological data. Levels of myofibroblastic stroma varied from 0–46%, with a median of 15.1% and a standard deviation of 7.5. The myofibroblastic stromal reaction was statistically greater in grade 2 and 3 tumors (p = 0.029). Furthermore, there was a trend for worse progression-free survival in the group of node-negative tumors with strong smooth-muscle actin stromal expression (Log rank = 0.075). The present study demonstrates that the myofibroblastic reaction of breast invasive carcinoma of no special type is not merely a passive reaction, but seems to be an integral part of the neoplastic process by facilitating tumor progression and invasion. Additional, larger studies on mechanisms of stromal change are needed and may potentially lead to novel treatments.

肿瘤进展源于肿瘤细胞与细胞外微环境之间的复杂相互作用。在乳腺癌中，间质微环境被认为在促进肿瘤生长、进展与侵袭过程中发挥核心作用。本研究采用数字图像分析仪，对154例乳腺非特殊类型浸润性癌（invasive breast carcinoma of no special type）切除标本的间质进行定量分析。针对间质含量与患者生存情况、无进展生存期与临床病理数据之间的关联开展了统计学分析。肌成纤维细胞间质（myofibroblastic stroma）占比范围为0%~46%，中位数为15.1%，标准差为7.5。2级与3级肿瘤的肌成纤维细胞间质反应强度在统计学上显著更高（p=0.029）。此外，在平滑肌肌动蛋白（smooth-muscle actin）间质表达较强的淋巴结阴性肿瘤患者组中，无进展生存期呈现出较差的趋势（Log-rank检验=0.075）。本研究表明，乳腺非特殊类型浸润性癌的肌成纤维细胞间质反应并非单纯的被动应答，而是通过促进肿瘤进展与侵袭，成为肿瘤发生发展过程中的不可或缺的组成部分。未来需要开展更多、更大样本量的研究以阐明间质改变的具体机制，该方向或可催生全新的治疗方案。