Expression of proteoglycan versican in in situ breast lesions: relations between stromal changes, histotype, and...

The role of the stromal constituents in the natural history of breast cancers is still poorly defined. The aim of the present study was to evaluate the expression of proteoglycan versican, a constituent of desmoplastic stroma of invasive carcinomas, in preinvasive breast lesions. We selected 41 cases of breast carcinoma: 28 pure in situ lesions and 13 invasive lesions with in situ-associated lesions. The study provided evidence that versican is strongly expressed in the perilesional stroma of a subclass of ductal in situ carcinomas, and that the extension of versican immunostaining is statistically related to the high grade (G3) category (54% of diffuse expressors; p=0.01), and with a comedo pattern (67% of diffuse expressors, p=0.003). On the other hand, the expression of versican in the cases of classic lobular in situ carcinomas that we selected for the study was confined to the anatomical structures that usually contain the proteoglycan in adult breast tissues. In our cohort, versican synthesis was found to be associated with spindle-shaped elements with myofibroblastic phenotype, as in the stroma of invasive carcinoma. These data, taken together with evidence from previous studies on proteins strongly related to versican, suggest that various histotypes of breast in situ carcinomas could follow different pathways of epithelial stromal interactions. In particular a category of in situ lesions shows constituents of desmoplastic stroma before the manifestation of the morphological signs of invasion. Study of the connective tissue modifications that trigger the pivotal phase of invasion could provide new prospects in oncology.