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SOX9, an important factor for testis determination and chondrogenesis, was previously detected in the nucleus of testicular sertoli cells and chondrocytes but was found in only a subset of ovarian sertoli cell tumors, carcinoid tumors, and endometrioid carcinomas, and occasionally only in the cytoplasm of those cells. SOX9 has also been detected in metaplastic carcinomas of the breast exhibiting chondroid differentiation so it became of interest to examine SOX9 in other breast carcinomas and normal breast. Normal breast lobules were studied immunohistochemically for SOX9 along with examples of metaplastic breast carcinoma exhibiting chondroid differentiation, lobular neoplasia (ALH/LCIS), invasive lobular carcinomas, and ductal carcinomas (invasive and in situ). SOX9 was identified solely in the nucleus in over 90% of the normal breast epithelial cells examined. In 10 of 12 breast carcinomas exhibiting chondroid metaplasia, and in 15 of 16 invasive lobular carcinomas, SOX9 was present primarily in the nucleus much like that seen in normal breast epithelium. In 14 of 20 invasive ductal carcinomas, however, it was missing or identified mainly in the cytoplasm of the malignant cells. The functional importance of SOX9 in the breast is unknown although transcription factors involved with the development of certain tissues may have similar capabilities in other organs. The retention of SOX9 in the nucleus of metaplastic or lobular carcinomas could indicate some functional expression of this protein in these tumors with an even more compelling reason why it is often restricted to the cytoplasm, or missing, in ductal carcinomas of the breast.

Intracellular Location of the SOX9 Protein in Breast Disease