5087

Purpose: The Na+/I- symporter (NIS) is a plasma membrane glycoprotein that mediates active iodide (I-) transport in the thyroid, salivary gland, gastric mucosa and lactating breast. Endogenous functional NIS expression is also found in 70% of breast cancers including estrogen receptor (ER) positive and negative as well as Her2 positive and negative tumors. Radioactive iodide (131I) therapy has been used for decades to successfully ablate thyroid cancer metastases. The identification of functional NIS expression combined with the well-established clinical benefits of radiation therapy have given impetus to our working hypothesis that 131I radiotherapy could become a highly selective anticancer therapy for breast cancer patients with strong NIS expression. To further define the tumor subtypes expressing NIS, we investigated the protein expression profile of basal and luminal cytokeratins (CK), estrogen and progesterone receptor (ER/PR), and Her2 in a high-density tissue microarray derived from a Chinese population.

Methods: Immunohistochemistry for ER, PR, Her2, CK5/6, and CK7/8 (CAM5.2) was performed on a Chinese cohort consisting of 108 invasive breast carcinomas, 5 ductal carcinoma in situ (DCIS), 19 mammary fibroadenomas and 17 normal breast tissues. The tissue microarray was selected from sequential pathology specimens at the First Affiliated Hospital of SunYatsen University (GuangZhou, China). Tumor nuclear grade was evaluated in invasive lesions with hematoxylin and eosin staining. Tissue microarray data were read by at least two independent pathologists and graded using institutional grading criteria for microarray.

Results: NIS expression was observed in 37% (40/108) of invasive mammary carcinomas and among those 30% (12/40) were strongly immunopositive. As in many thyroid cancers, the predominant distribution of NIS was intracellular. NIS expression positively correlated with tumor nuclear grade (P=0.001).

The NIS positive cores were mainly negative for Her2, with Her2 being overexpressed in only 3 cores (7.5%). Conversely, over 77% of the NIS cores were immunopositive (grade 1 and higher) for ER. Regarding the cytokeratins status, no staining (> score 2) was observed for CK 5 and 6, but NIS was associated in 28 occurences (70%) with positive staining (score >2) for luminal cytokeratins 7 and 8.

Conclusions: Immunochemical positivity for NIS was detected in 37% of a Chinese cohort characterized mainly as luminal-like, Her2 negative (85%) and with an overall ER/PR positivity of 55.5%. The positive correlation we observed between NIS expression and high tumor grade (associated with a worse prognosis) could make NIS a highly valuable target for selective cancer therapy.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA