Androgens exert growth inhibitory effects on estrogen receptor and progesterone receptor-negative breast cancer cell lines that show androgen receptor expression. These laboratory findings may be translated into inexpensive alternative therapies for hormone receptor-negative invasive breast cancers. Our aim was to systematically evaluate androgen receptor expression by immunohistochemistry in invasive breast cancers. Androgen receptor (clone AR441, Dako) expression was analyzed on 189 well-characterized consecutive invasive breast carcinomas represented with threefold redundancy on tissue microarrays. Androgen receptor expression was semi-quantitated using a histochemical score-like method and a score 410 was considered positive. Of the 189 consecutive invasive breast cancers, 151 (80%) were positive and 38 (20%) were negative for androgen receptor. The majority (95%) of estrogen receptor-positive tumors were also androgen receptor positive. Of the estrogen receptor-negative tumors, androgen receptor reactivity was seen in 3 of 30 (10%) triple-negative cases and in 5/8 (63%) estrogen receptor-negative/progesterone receptor-negative/HER2 þ cases. Six of eight estrogen receptor-negative/androgen receptor-positive cases showed apocrine differentiation. Androgen receptor expression in estrogen receptor-positive cases was associated with smaller tumor size (P ¼ 0.0001), lower Nottingham grade (P ¼ 0.002) and less frequent tumor cell necrosis (P ¼ 0.0001). Androgen receptor expression in estrogen receptor-negative tumors was associated with lower Nottingham grade (P ¼ 0.005) and apocrine differentiation (P ¼ 0.039). In conclusion, most estrogen receptor-positive breast tumors also express androgen receptor. Androgen receptor expression in estrogen receptor-negative/ progesterone receptor-negative/HER2 þ tumors (which commonly show apocrine differentiation) and a subset of triple -negative apocrine tumors suggest that these tumors together comprises the 'molecular apocrine' group described previously. However, these findings should be further confirmed on larger series of triplenegative and estrogen negative/progesterone negative/HER2 þ tumors. Androgen receptor-targeted therapy in estrogen/progesterone receptor-negative tumors may provide an inexpensive alternative to usual high-dose chemotherapy with or without trastuzumab. Keywords: androgen receptor; breast carcinoma; apocrine differentiation Breast cancer represents a diverse group of tumors that vary in clinical behavior and response to therapy. Currently, invasive breast cancer is treated by multi-modality therapy. Approximately 75% of breast cancers are positive for estrogen (ER) and/or progesterone (PR) receptor protein expression. This group of tumors is generally responsive to selective estrogen receptor modulators, 1 with relative resistance seen in a subset of tumors co-expressing HER2. 2 The remaining 20-25% of breast cancers are ER and PR negative and are not amenable to selective estrogen receptor modulators. This hormone receptor-negative group include...

Background Thyroid papillary microcarcinoma (TPMC) is an incidentally discovered papillary carcinoma that is ≤ 1.0 cm in size. Most TPMCs are indolent, whereas some behave aggressively. The aim of the study was to evaluate whether the combination of BRAF mutation and specific histopathological features allows risk stratification of TPMC. Methods A group of aggressive TPMC was selected based on the presence of lymph node metastasis or tumor recurrence. A group of non-aggressive tumors included TPMCs matched for age, gender, and tumor size, but with no extrathyroidal spread. Molecular analysis was performed and histological slides were scored for multiple histopathological criteria. A separate validation cohort of 40 TPMC was evaluated. Results BRAF mutation was detected in 77% of aggressive TPMC and 32% of non-aggressive tumors (p=0.001). Several histopathological features showed significant difference between the groups. Using multivariate regression analysis, a molecular-pathological (MP) score was developed that included BRAF status and three histopathological features: superficial tumor location, intraglandular tumor spread/multifocality, and tumor fibrosis. By adding the histologic criteria to BRAF status, sensitivity was increased from 77% to 96% and specificity from 68% to 80%. In the independent validation cohort, the MP score stratified tumors into low, moderate, and high risk groups, with the probability of lymph node metastases or tumor recurrence of 0, 20%, and 60%, respectively. Conclusions BRAF status together with several histopathological features allow clinical risk stratification of TPMC. The combined molecular-pathological risk stratification model is a better predictor of extrathyroidal tumor spread than either mutational or histopathological findings alone.

The results of this study suggested that patients with preoperative non-dialysis-dependent renal insufficiency have more favorable outcome when revascularization is done off pump. Avoidance of CPB results in (1) a reduction in the incidence of postoperative renal failure; (2) a reduction in the need for new dialysis; and (3) improved in-hospital and midterm survival.