Persistent <i>FC PIK3ca*</i> tumors demonstrated a differential response in pS6 in the hyperplastic and tumor tissue following rapamycin treatment.

<p>A tumor resistant to rapamycin (top in each panel) and a tumor from a placebo-treated <i>FC PIK3ca*</i> mouse (bottom in each panel) were embedded in the same histological block. A similar phenotype and proliferation rate were noted on H&E and Ki67 staining, respectively (<i>A</i> and <i>B</i>). No significant difference in pAKT was seen between the tumors from the placebo and rapamycin treated mice (<i>C</i>). In the tissue from the placebo-treated mouse, increased pS6 was seen in the tumor tissue and overlying hyperplastic tissue as expected (<i>D</i>). Interestingly, in the tissue from the rapamycin-treated <i>FC PIK3ca*</i> mouse, decreased pS6 is noted in the hyperplastic tissue, but increased pS6 signaling remains in the resistant tumor tissue despite rapamycin treatment. This indicates that persistent pS6 setting within the tumors may be the mechanism of tumor resistance. This same staining pattern was observed in all tumors (3/3) with some neoplastic cells remaining after treatment with rapamycin that were examined. Size bars: <i>A</i>, <i>C</i> and <i>D</i>, 1 mm; <i>B</i>, 500 µm.