The interplay between a tumor and its environment is exemplified by the morphological changes observed in the stroma of human breast cancer. These changes are evident as stromal myxoid changes. Hyaluronan, an extracellular polysaccharide that has been implicated in invasion, is one of the major constituents of the stromal myxoid changes. This study evaluated the association of these stromal changes with axillary node status, tumor grade, and mortality. The prognostic value of the stromal myxoid changes was evaluated in patients with negative axillary nodes with 10 years of follow-up. Our results showed a high level of reproducibility of our stromal myxoid changes grading system (overall kappa ؍ 0.68). Image analysis semiquantification showed marked correlation of a strong stromal hyaluronan signal with high-grade stromal myxoid changes. In a multiple logistic regression analysis, positive nodes were associated with stromal myxoid changes, tumor size, desmoplasia, lymphocytic infiltration, high tumor grade, tumor emboli, and multifocality. Stromal myxoid changes were also associated with young age and lymphatic embolizations (P < .001). Overall, there is a weak correlation between mortality and stromal myxoid changes (P < .01). Mortality was more evident with high stromal myxoid changes grades and tumor size >2 cm (P < .008). However Cox multivariate analysis fail to show stromal myxoid changes as an independent prognostic factor. In conclusion, stromal myxoid changes with high hyaluronan concentration are strongly associated with positive nodes, tumor grade, and lymphatic emboli, thereby identifying high-risk group and reinforcing the role of hyaluronan in invasion and metastasis.KEY WORDS: Breast cancer, Hyaluronan, Metastasis, Stroma.
Mod Pathol 2003;16(2):99 -107Lymph node and hematogenous distant metastases are the result of a cascade of enzymatic interactions. Part of this complex cascade takes place in the tumor environment, where malignant tumor cells detach from the primary tumor, adhere to components of the extracellular matrix, degrade them, and move through the stroma. Morphological and biochemical modifications of the different stromal components (cellular and noncellular) can either favor or inhibit this process. Therefore, the histopathological modifications of the stroma in response to a tumor could shed light on the biological mechanisms involved in invasion and metastasis. Stromal myxoid changes consists of a stromal reaction composed of an amphophilic or slightly basophilic vacuolated material that stains positively with Alcian Blue and is found among the collagen fibers. Hyaluronan is one of its major components. Tissues rich in hyaluronan entrap water and swell, leading to myxoid changes. It is known that hyaluronan synthesis is stimulated by the interaction between tumor and stromal cells (1-3). Hyaluronan has several physiological functions, such as water homeostasis and regulation of capillary growth; it also plays a role in cell recognition and migration (4). A strong relationship betwe...
