Stromal Changes are Associated with High P4HA2 Expression in Ductal Carcinoma in Situ of the Breast

Ductal carcinoma in situ (DCIS) of the breast is able to induce stromal changes, which likely reflect the crosstalk between DCIS and its microenvironment. These changes harbor prognostic information, although the interobserver variability of scoring stromal changes is moderate. A more robust evaluation of the DCIS-associated stroma is therefore needed. The aim of this study was to characterize P4HA2 expression, which is involved in collagen biosynthesis, in DCIS and to assess whether P4HA2 expression enables a more robust evaluation of the DCIS-associated stroma compared to histomorphology. This study included 410 patients with DCIS. Stromal changes were scored on hematoxylin/eosin-stained whole slides. P4HA2 expression in DCIS-associated stroma was assessed by whole slide immunohistochemistry. One hundred DCIS lesions were evaluated by seven pathologists to study the interobserver variability in the assessment of stromal changes and stromal P4HA2 expression. High P4HA2 expression in stromal fibroblasts was present in 14.1% of the patients. High P4HA2 expression was associated with the presence of periductal stromal changes (P = 0.004). The interobserver variability was similar for the assessment of stromal changes and the percentage of P4HA2-positive fibroblasts. Although we demonstrated a significant association between high P4HA2 expression in fibroblasts and the morphological presence of stromal changes, it seems unlikely that P4HA2 expression can be used as an alternative for the histopathological evaluation of the DCIS-associated stroma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10911-021-09504-4.