The heterogeneity of intraductal carcinoma of the prostate is associated with different efficacy of standard first-line therapy for patients with metastatic castration-resistant prostate cancer.

BACKGROUND: To explore whether metastatic castration-resistant prostate cancer (mCRPC) patients with distinct intraductal carcinoma of the prostate (IDC-P) subtypes respond differently to abiraterone and docetaxel treatment. METHODS: We retrospectively analyzed data of 170 mCRPC patients receiving abiraterone or docetaxel as first-line therapy. PSA response, PSA progression-free survival (PSA-PFS), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed based on the presence of IDC-P and its subpatterns. RESULTS: IDC-P was confirmed in 91/170 (53.5%) patients. Among them 36/91 (39.6%) and 55/91 (60.4%) harbored IDC-P patterns 1 and 2, respectively. Patients with IDC-P pattern 1 shared similar clinical outcomes to those without IDC-P in both abiraterone and docetaxel treatment. However, against cases without IDC-P or with IDC-P pattern 1, patients with IDC-P pattern 2 had markedly poorer prognosis in either abiraterone (mPSA-PFS: 11.9 vs. 11.1 vs. 6.1 months, p < 0.001; mrPFS: 18.9 vs. 19.4 vs. 9.6 months, p < 0.001) or docetaxel (mPSA-PFS: 6.2 vs. 6.6 vs. 3.0 months, p < 0.001; mrPFS: 15.1 vs. 12.6 vs. 5.5 months, p < 0.001) treatment. For patients without IDC-P, docetaxel had comparable therapeutic efficacy with abiraterone. However, the efficacy of docetaxel was significantly inferior to abiraterone in patients with either IDC-P pattern 1 (mPSA-PFS: 6.6 vs. 11.1 months, p = 0.021; mrPFS: 12.6 vs. 19.4 months, p = 0.027) or pattern 2 (mPSA-PFS: 3.0 vs. 6.1 months, p = 0.003; mrPFS: 5.5 vs. 9.6 months, p = 0.007). CONCLUSION: Compared to docetaxel, abiraterone exhibited better efficacy in patients with IDC-P of either pattern. However, IDC-P pattern 2 responded unsatisfactorily to either abiraterone or docetaxel therapy. Novel therapeutic strategies for IDC-P pattern 2 need further investigations.

Histological patterns and intra-tumor heterogeneity as prognostication tools in high grade serous ovarian cancers.

OBJECTIVE: High grade serous ovarian carcinoma (HGSOC) is the most common type of malignant ovarian neoplasm and the main cause of ovarian cancer related deaths worldwide. Although novel biomarkers such as homologous recombination deficiency testing have been implemented into the clinical decision-making algorithm since diagnosis, morphological classification and immunohistochemistry analysis are essential for diagnostic purpose. This study aims at identifying histologic and clinical features that can be predictive of patients' prognosis. METHODS: Morphological and architectural characterization including SET (Solid-Endometroid-Transitional)/Classic features was carried out in a cohort of 234 patients analyzing 695 slides. From each slide tumor infiltrating lymphocyte (TILs), the presence of necrosis, the number of mitoses, the presence of psammoma bodies, giant cells and atypical mitoses were recorded. Morphological heterogeneity was quantified by the Shannon's diversity index (SDI) considering the percentage of each architectural pattern per patient's slide. RESULTS: The frequency of architectural patterns and morphological variables varied with respect of the surgical strategy (primary debulking surgery vs interval surgery after neoadjuvant chemotherapy). HGSOCs exhibiting SET features had a longer overall as well as progression free survival. Among SET features, pseudo-endometrioid and transitional like patterns had the best outcome, while it was heterogenous for solid pattern, that had better outcome for BRCA 1 negative and less heterogeneous tumors. In patients submitted to neoadjuvant chemotherapy a higher intratumor heterogeneity as defined by SDI was a negative independent prognostic factor. CONCLUSIONS: A comprehensive histological examination considering architectural patterns and their heterogeneity can help in prognostication of HGSOCs.

PTEN Loss and PD-L1 Expression of Different Histological Patterns of Prostate Cancer.

AIMS: Although several studies have evaluated PTEN loss in Prostatic Adenocarcinoma (PCa), PTEN loss correlation with different histological patterns only has a few studies. Although several studies have evaluated PD-L1 expression in PCa and its correlation with Gleason scores, as far as we know, there are no prior studies that have included a comparison between PD-L1 expression and histological patterns of PCa. This study aims to evaluate PTEN loss and PD-L1 expression by immunohistochemistry in different histological patterns of PCa. METHODS: The current study included consecutive 98 radical prostatectomy specimens with 151 foci with different Gleason Grade (GG) patterns. RESULTS: The highest frequency of PTEN loss was observed in GG4 cribriform and glomeruloid patterns (59.3%, p < 0.001). Combined score (CS) PD-L1 positivity was observed in fourteen patients (14.2%). Tumor cell (TC) and tumor-associated inflammatory cells (IC) PD-L1 positivity was observed in 10 (10.2%) and 7 (7.1%) patients. The highest frequency of PD-L1 expression was observed in the GG5 pattern, and between GG4 patterns, the irregular pattern had the highest PD-L1 positivity. CONCLUSIONS: In conclusion, in our cohort of consecutive unselected cases of prostatic carcinoma, we observed the highest PTEN loss rate in the GG4 cribriform and glomeruloid pattern and the highest PD-L1 expression rate in the GG5 and GG4 irregular patterns. These results may predict molecular differences between different histological patterns in PCa and may be used to inform a treatment decision. Future studies should investigate these differences between histological patterns of PCa to predict response to immunotherapy in larger cohorts.

Retailer's Dual Role in Digital Marketplaces: Reference Architectures for Retail Information Systems.

Digital marketplaces have entered the retail sector and have proven to be a successful business model compared to traditional retailing. Established retailers are increasingly launching digital marketplaces as well as participating in marketplaces of pure online companies. Retailers transforming to digital marketplaces orchestrate formerly independent markets and enable retail transactions between participants while simultaneously selling articles from their own assortment to customers in the digital marketplace (dual role). A retailer's dual role must be supported by retail information systems. However, this support is not explicitly represented in existing reference architectures for retail information systems. Thus, we propose to develop a reference architecture for retail information systems that facilitates the orchestration of supply- and demand-side participants, selling their own articles, and providing innovation platform services. We apply a design science research approach and present nine architectural requirements that a reference architecture for a multi-sided market business model in retail needs to fulfill (dual role, additional participants, affiliation, matchmaking, variety of services, innovation services, smart services, aggregated assortment, and boundary resources) from the rigor cycle. From the first design iteration, we propose four exemplary, conceptual architectural patterns as a solution for the requirements (matchmaking for participants, innovation platform services, boundary resources, and aggregated assortment). These patterns can form a conceptual reference architecture that guides the design and implementation of information systems.

Assessing the correlation between FDG PET findings of IDC breast carcinoma and histopathology of coexisting ductal carcinoma in-situ.

BACKGROUND: Ductal carcinoma in-situ (DCIS) often coexists with invasive ductal carcinoma (IDC) of the breast. DCIS is considered as a non-obligate precursor of IDC when both coexist. 18F-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) imaging is commonly used in the staging and follow-up assessment of breast cancer. In this study, we aimed to assess if there is any correlation between primary tumor PET and histopathology findings and histopathological features of the coexisting DCIS. MATERIAL AND METHODS: FDG PET/CT images and histopathology results of the patients with newly diagnosed breast cancer (IDC) with coexisting DCIS were analyzed in this retrospective study. The grade and size of the primary tumor and histopathological features of the coexisting DCIS (nuclear grade and architectural pattern) were obtained from the postoperative histopathology results. Maximum standardized uptake values (SUV: SUVmax and SULmax) of the primary tumor normalized by weight and lean body mass were measured. Statistical analysis was performed to assess the correlation between various parameters of IDC and DCIS. RESULTS: This study included sixty-two (62) patients with IDC-DCIS. Primary tumor grade was significantly correlated and associated with the nuclear grade of the coexisting DCIS (polychoric correlation r = 0.736, and Fisher exact test, PV < 0.001, respectively). Primary tumor SUV was not correlated with the nuclear grade and architectural pattern of the coexisting DCIS (polyserial correlation r = 0.172, PV = 0.155, and Point Bi-Serial correlation r = -0.009, PV = 0.955, respectively). Median primary tumor size was marginally significantly different among DCIS nuclear grades but it was not significantly different in comedo and non-comedo cases (Kruskal-Wallis test PV = 0.053, and Mann-Whitney U test PV = 0.890, respectively). CONCLUSIONS: Primary tumor grade is correlated with the nuclear grade of the coexisting DCIS. SUV of primary tumor does not seem to be correlated with the histopathological features of coexisting DCIS (nuclear grade and architectural pattern) but this may be further studied in a larger number of patients.

Fine-needle aspiration cytology of gallbladder with an attempt of cytomorphological classification.

BACKGROUND: Image-guided fine-needle aspiration has emerged as an effective diagnostic tool for precise diagnosis of deep-seated lesions. Although occasional studies have made an attempt to classify the gallbladder carcinoma on cytology, literature lacks the standardized cytological nomenclature system used for it. The present study was conducted to study the role of fine-needle aspiration cytology (FNAC) in diagnosis of gallbladder lesions with an attempt of cytomorphological classification. METHODS: The study included cases of image-guided FNAC of the gallbladder over a period of 3½ years. An attempt was made to categorize gallbladder lesions on basis of architectural and cytomorphological features along with analysis of management. RESULTS: The study included 433 cases and lesions were categorized on FNAC into five categories ranging from Category 1 (inadequate), Category 2 (negative for malignancy), Category 3 (atypical cells), Category 4 (highly atypical cells suggestive of malignancy), and Category 5 (positive for malignancy). The most common architectural pattern observed on FNAC of neoplasm was sheets and acini with predominance of columnar cells and adenocarcinoma being the most common malignancy. The histopathological diagnosis was available in 93 cases with cytohistopathological concordance of 94.4% in malignant cases. CONCLUSIONS: Image-guided FNAC plays an important role in diagnosis of gallbladder lesions with minimal complications. The cytomorphological classification of gallbladder lesions provides an effective base for accurate diagnosis and management. Category 3 and 4 are the most ambiguous category on FNAC which should be managed by either repeat FNAC or surgery in the light of worrisome radiological features. The vigilant examination of architectural pattern and cytomorphological features of the smears may be helpful in clinching the diagnosis and precisely subtyping malignant tumors along with prognostication of these tumors.

A tool written in Scala for preparation and analysis in MD simulation and 3D-RISM calculation of biomolecules.

Researchers studying biomolecules require easy-to-use, customizable tools allowing them to effectively use other molecular science packages written for molecular dynamics (MD), quantum chemistry, statistical mechanics, and molecular graphics. This paper presents a Scala tool for the computational science of biomolecules (STCSB) developed in Scala, which allows users to prepare and run MD simulations, as well as perform three-dimensional reference interaction site model (3D-RISM) calculations of biomolecules. Features of the STCSB include the following: (1) a cross-platform application running on a Java virtual machine; (2) handling hierarchical XML-based data formats such as the protein data bank markup language (PDBML); (3) prepared application programming interfaces (APIs) with both character user interface (CUI) and graphical user interface (GUI) options; (4) prepared APIs for molecular graphics; and (5) a scalable source code based on the Model-View-Controller (MVC) architectural pattern.

Histopathological Prognostic Factors in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (CCRCC) are the most frequent type of renal cell carcinoma. Fuhrman grade and tumor stage are prognostic factors with great importance in survival rate. This study was performed on 75 cases of CCRCC diagnosed by the Anatomical Pathology Laboratory of the County Clinical Emergency Hospital of Craiova between 2014 and 2017. The biological material was represented by pieces of nephrectomy. The cases were analyzed on two criteria: epidemiology (age, sex) and histopathology (Fuhrman grade, tumor stage, architectural pattern, sarcomatoid transformation, and necrosis). Statistical analysis was done using Chi Square tests in IBM SPSS software. Average diagnosis age of CCRCC was 58.8±10.2 years, predominantly in male patients (66.7%). Tumor sizes were between 2 and 14cm, with an average of 6.7±2.9cm. Most cases were determined to be tumor stage III (60%) and Fuhrman grade 2 (56%), followed, in order of frequency, by tumor stages I and II (28% and 10.7%) and Fuhrman grades 3 and 1 (21.3% and 20%). High Fuhrman grade CCRCC were significantly associated with advanced tumor stage (p<0.05, χ2 test). Most cases presented a mixed pattern, significantly associated with advanced tumor stages (p<0.05, χ2 test). Even though the presence of sarcomatoid transformation was more frequent in advanced tumor stages, it wasn't significantly linked to them (p<0.05, χ2 test). Conclusions: Analyzed histopathological parameters are useful for determining CCRCC aggressiveness. CCRCC in advanced tumor stages is associated with high Fuhrman grade and mixed architectural pattern.

Pulmonary mucinous adenocarcinomas: architectural patterns in correlation with genetic changes, prognosis and survival.

Of pulmonary adenocarcinomas, about 25-30 % of cases is of a mucinous type. Mucinous adenocarcinomas are regarded as more aggressive compared to their non-mucinous counterparts. Invasive mucinous adenocarcinoma, colloid, and enteric adenocarcinomas are variants within adenocarcinomas. We investigated 76 invasive mucinous adenocarcinomas, including colloid variants, for predominant and secondary patterns, their different form of mucin storage and release, expression of cytokeratin 7 and 20, TTF1 and CDX2, MUC1, 2, and 5AC proteins, p14 and p16 proteins, possible rearrangements for EML4ALK and ROS1, as well as KRAS mutational status, and correlated this with survival. For comparison, 259 non-mucinous adenocarcinomas were selected. Overall survival for invasive mucinous adenocarcinomas corrected for T and N stage was not different from their non-mucinous counterpart. Most were of an acinar pattern. Neither pattern, nor type of mucin storage and release, such as luminal, extracellular, or goblet cell type had any influence on survival. Of adenocarcinomas expressing CK20, all but one expressed TTF1 either strongly or at least focally, and 8 co-expressed CDX2 focally. Most mucinous adenocarcinomas expressed either MUC1 or MUC5AC proteins, but rarely MUC2, while a few cases co-expressed both or all three. Loss of p16 expression correlated with worse outcome. KRAS mutation was found in 56 % of mucinous adenocarcinomas. Mutational status was neither correlated with architectural pattern nor survival. Codon 12 mutations were most frequent, and one case presented with KRAS mutations in codon 12 and 61. Goblet cell variants of mucinous adenocarcinomas presented predominantly with codon 12 mutations, while all colloid variants had KRAS mutation. Two cases had EML4 and ALK1 rearranged; ROS1 rearrangement was not found. Mucinous adenocarcinomas behave similar to non-mucinous variants. TNM stage is the most important factor followed by p16 loss predicting overall survival.