Nuclei Detection and Segmentation of Histopathological Images Using a Feature Pyramidal Network Variant of a Mask R-CNN.

Cell nuclei interpretation is crucial in pathological diagnostics, especially in tumor specimens. A critical step in computational pathology is to detect and analyze individual nuclear properties using segmentation algorithms. Conventionally, a semantic segmentation network is used, where individual nuclear properties are derived after post-processing a segmentation mask.

Detection of Cellular Senescence Reveals the Existence of Senescent Tumor Cells within Invasive Breast Carcinomas and Related Metastases.

Oncogene-induced senescence is thought to constitute a barrier to carcinogenesis by arresting cells at risk of malignant transformation. However, numerous findings suggest that senescent cells may conversely promote tumor growth and metastatic progression, for example, through the senescence-associated secretory phenotype (SASP) they produce. Here, we investigated the degree to which senescent tumor cells exist within untreated human primary breast carcinomas and whether the presence of senescent cancer cells in primary tumors is recapitulated in their matched lymph node metastases.

Functional Characterization of Circulating Tumor Cells (CTCs) from Metastatic ER+/HER2- Breast Cancer Reveals Dependence on HER2 and FOXM1 for Endocrine Therapy Resistance and Tumor Cell Survival: Implications for Treatment of ER+/HER2- Breast Cancer.

Mechanisms of acquired endocrine resistance and late recurrence in patients with ER+/HER2- breast cancer are complex and not fully understood. Here, we evaluated mechanisms of acquired resistance in circulating tumor cells (CTCs) from an ER+/HER2- breast cancer patient who initially responded but later progressed under endocrine treatment. We found a switch from ERα-dependent to HER2-dependent and ERα-independent expression of FOXM1, which may enable disseminated ER+/HER2- cells to re-initiate tumor cell growth and metastasis formation in the presence of endocrine treatment.

Improved detection of sentinel lymph node metastases allows reliable intraoperative identification of patients with extended axillary lymph node involvement in early breast cancer.

An improved procedure that allows accurate detection of negative sentinel lymph node (SLN) and of SLN macrometastases during surgery would be highly desirable in order to protect patients from further surgery and to avoid unnecessary costs. We evaluated the accuracy of an intraoperative procedure that combines touch imprint cytology (TIC) and subsequent frozen section (FS) analysis. 2276 SLNs from 1072 patients with clinical node-negative early breast cancer were evaluated during surgery using TIC.

Evaluation of HER2 expression in urothelial carcinoma cells as a biomarker for circulating tumor cells.

Background: Detection of circulating tumor cells (CTC) by techniques based on epithelial cell adhesion molecule (EpCAM) is suboptimal in urothelial carcinoma (UC). As HER2 is thought to be broadly expressed in UC, we explored its utility for CTC detection.

Methods: HER2 and EpCAM expression was analyzed in 18 UC cell lines (UCCs) by qRT-PCR, western blot and fluorescence-activated cell scanning (FACS) and compared to the strongly HER2-expressing breast cancer cell line SKBR3 and other controls.

'Normalizing' the malignant phenotype of luminal breast cancer cells via alpha(v)beta(3)-integrin.

Reestablishing tissue organization of breast cancer cells into acini was previously shown to override their malignant phenotype. In our study, we demonstrate that alpha(v)beta(3) integrin (Int-αvβ3), previously shown to play a role in cancer progression, promoted differentiation and growth arrest of organoids derived from luminal A breast cancer cells grown in their relevant three-dimensional microenvironment. These organoids differentiated into normal-like acini resembling a benign stage of breast tissue.

Detection of cellular senescence within human invasive breast carcinomas distinguishes different breast tumor subtypes.

Oncogene-induced senescence is thought to act as a barrier to tumorigenesis by arresting cells at risk of malignant transformation. Nevertheless, numerous findings suggest that senescent cells may conversely promote tumor progression through the development of the senescence-associated secretome they produce. It is likely that the composition and the physiological consequences mediated by the senescence secretome are dependent on the oncogenes that trigger the senescence program.

c-met is overexpressed in type I ovarian cancer: Results of an investigative analysis in a cohort of consecutive ovarian cancer patients.

The tyrosine kinase c-met alters signaling cascades such as the BRAF-MAPK and PI3K-PKB pathways. These alterations are involved in the carcinogenesis of type I but not type II ovarian cancer (OC). Therefore, the present study investigated the patterns of c-met expression in a cohort of consecutive patients with OC.

Feasibility of induced metabolic bioluminescence imaging in advanced ovarian cancer patients: first results of a pilot study.

Purpose: The precise determination of energy metabolites is challenged by the heterogeneity of their distribution, their rapid changes after surgical resection and the architectural complexity of malignancies. Induced metabolic bioluminescence imaging (imBI) allows to determine energy metabolites in tissue sections and to co-localize these with histological structures based on consecutive sections stained with HE. In this prospective pilot study patients with suspected advanced ovarian cancer (OC) were enrolled to prove the feasibility of imBI.

Validation of a two-tier grading system in an unselected, consecutive cohort of serous ovarian cancer patients.

Purpose: New insights into the carcinogenesis of ovarian cancer (OC) lead to the definition of low-grade and high-grade serous OC. In this study, we validated the MD Anderson Cancer Center (MDACC) two-tier grading system and compared it with the traditional three-tier grading system as suggested by the International Federation of Gynecology and Obstetrics (FIGO).

Methods: Consecutive patients with serous OC were enrolled.

Prognostic influence of cyclooxygenase-2 protein and mRNA expression in node-negative breast cancer patients.

Background: Cyclooxygenases (COX) play a key role in prostaglandin metabolism and are important for tumor development and progression. The aim of this study was to analyze the prognostic impact of COX-2 expression in a cohort of lymph node-negative breast cancer patients not treated in the adjuvant setting.

Methods: COX-2 expression was determined by immunohistochemistry (IHC) in tumor tissue of 193 node-negative breast cancer patients.

Overexpression of epithelial cell adhesion molecule protein is associated with favorable prognosis in an unselected cohort of ovarian cancer patients.

Purpose: The aim of this study was to evaluate the prognostic influence of epithelial cell adhesion molecule (EpCAM) in an unselected cohort of ovarian cancer (OC) patients.

Methods: Expression of EpCAM was determined by immunohistochemistry in an unselected cohort of 117 patients with OC. Univariable and multivariable Cox regression analyses adjusted for age, tumor stage, histological grading, histological subtype, postoperative tumor burden and completeness of chemotherapy were performed in order to determine the prognostic influence of EpCAM.

Ki-67 as an independent prognostic factor in an unselected cohort of patients with ovarian cancer: results of an explorative, retrospective study.

The identification of prognostic markers has clinical implications in epithelial ovarian carcinoma (EOC). Here, we studied markers for proliferation (Ki-67), endocrine regulation [progesterone receptor (PR), estrogen receptor (ER)], and invasion [urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor (PAI-1)]. All patients with available follow-up information and EOC tissue, who were treated at our institution between 1997 and 2004, were enrolled in the present study.

The transcription factors TBX2 and TBX3 interact with human papillomavirus 16 (HPV16) L2 and repress the long control region of HPVs.

The minor capsid protein L2 of human papillomaviruses (HPVs) has multiple functions during the viral life cycle. Although L2 is required for effective invasion and morphogenesis, only a few cellular interaction partners are known so far. Using yeast two-hybrid screening, we identified the transcription factor TBX2 as a novel interaction partner of HPV type 16 (HPV16) L2.

Ep-CAM RNA expression predicts metastasis-free survival in three cohorts of untreated node-negative breast cancer.

Epithelial cell adhesion molecule (Ep-CAM) recently received increased attention as a prognostic factor in breast cancer. We aimed to validate the influence of Ep-CAM RNA expression in untreated node-negative breast cancer. Ep-CAM RNA expression was evaluated utilizing microarray-based gene-expression profiling in 194 consecutive node-negative breast cancer patients with long-term follow-up not treated in the adjuvant setting.

Prognostic effect of epithelial cell adhesion molecule overexpression in untreated node-negative breast cancer.

Purpose: Epithelial cell adhesion molecule (Ep-CAM) recently received increased attention not only as a prognostic factor in breast cancer but also as a potential target for immunotherapy. We examined Ep-CAM expression in 402 consecutive node-negative breast cancer patients with long-term follow-up not treated in the adjuvant setting.

Experimental Design: Ep-CAM expression was evaluated by immunostaining.