Development of a spatially offset Raman spectroscopy probe for breast tumor surgical margin evaluation.

The risk of local recurrence for breast cancers is strongly correlated with the presence of a tumor within 1 to 2 mm of the surgical margin on the excised specimen. Previous experimental and theoretical results suggest that spatially offset Raman spectroscopy (SORS) holds much promise for intraoperative margin analysis. Based on simulation predictions for signal-to-noise ratio differences among varying spatial offsets, a SORS probe with multiple source-detector offsets was designed and tested. It was then employed to acquire spectra from 35 frozen-thawed breast tissue samples in vitro. Spectra from each detector ring were averaged to create a composite spectrum with biochemical information covering the entire range from the tissue surface to ∼2 mm below the surface, and a probabilistic classification scheme was used to classify these composite spectra as "negative" or "positive" margins. This discrimination was performed with 95% sensitivity and 100% specificity, or with 100% positive predictive value and 94% negative predictive value.

Inhibition of mammalian target of rapamycin is required for optimal antitumor effect of HER2 inhibitors against HER2-overexpressing cancer cells.

PURPOSE: A significant fraction of HER2-overexpressing breast cancers exhibit resistance to the HER2 antibody trastuzumab. Hyperactivity of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway confers trastuzumab resistance, and mammalian target of rapamycin (mTOR) is a major downstream effector of PI3K/AKT. Therefore, we examined whether mTOR inhibitors synergize with trastuzumab. EXPERIMENTAL DESIGN: Immunocompetent mice bearing HER2(+) mammary tumors were treated with trastuzumab, the mTOR inhibitor rapamycin, or the combination. Mice were imaged for tumor cell death using an optical Annexin-V probe and with [(18)F]FDG positron emission tomography. The signaling and growth effects of the mTOR inhibitor RAD001 on HER2(+) cells treated with trastuzumab or lapatinib were evaluated. RESULTS: Treatment of mice with trastuzumab plus rapamycin was more effective than single-agent treatments, inducing complete regression of 26 of 26 tumors. The combination induced tumor cell death (Annexin-V binding) and inhibited FDG uptake. Rapamycin inhibited mTOR and tumor cell proliferation as determined by phosphorylated S6 and Ki-67 immunohistochemistry, respectively. In culture, the combination of RAD001 plus trastuzumab inhibited cell growth more effectively than either drug alone. Trastuzumab partially decreased PI3K but not mTOR activity. Knockdown of TSC2 resulted in HER2-independent activation of mTOR and dampened the response to trastuzumab and lapatinib. Treatment with the HER2 inhibitor lapatinib decreased phosphorylated S6 and growth in TSC2-expressing cells but not in TSC2-knockdown cells. CONCLUSIONS: Inhibition of PI3K and mTOR are required for the growth-inhibitory effect of HER2 antagonists. These findings collectively support the combined use of trastuzumab and mTOR inhibitors for the treatment of HER2(+) breast cancer.

Penile metastasis of chondrosarcoma of the jaw.

Metastasis to the penis is an unusual event. Bladder and prostate tumors are the main sources of penile metastasis. Other sites include the rectosigmoid, kidney, and, less frequently, the pancreas, liver, nasopharynx, and lung. Other sources include malignant melanoma and Burkitt's lymphoma. The differential diagnosis includes idiopathic priapism, venereal or infectious disease, tuberculosis, Peyronie's disease, and primary penile tumor. Chondrosarcoma of the jaw is responsible for 10% of all chondrosarcomas that originate with craniofacial bones. Its behavior is usually characterized by local aggression; however, distant metastasis is uncommon. We report a case of chondrosarcoma of the jaw with penile metastasis. This is the first case described in published medical reports.

Evaluation of breast cancer metastases in pleural effusions by molecular biology techniques.

The aim of this study was to evaluate the presence of allelic loss in chromosomal regions previously described as exhibiting loss of heterozygosity (LOH) during breast carcinogenesis, in pleural effusions of breast cancer patients. LOH was analyzed in three loci (1p32, 7q31, and 17q21). We studied 41 samples of pleural effusions from breast cancer patients (24 positive for neoplastic cells, 14 suspected, and 3 negative cases) and breast tissues from the patients (primary tumors and nonneoplastic adjacent tissue). DNA was extracted from pleural effusions, primary tumor, and adjacent normal tissue. LOH was evaluated by polymerase chain reaction assay and was observed in 38% of pleural effusions positive for neoplastic cells, and in 36% of suspected cases where morphology only did not allow the diagnosis of malignancy. We conclude that LOH analysis in pleural effusions of breast cancer patients is able to identify metastases in cases where morphologic analysis becomes difficult.