Treatment of metastatic melanoma has dramatically improved in recent years, thanks to the development of immunotherapy and BRAF-MEK-targeted therapies. However, these developments revealed marked heterogeneity in patient response, which is yet to be fully understood. In this work, we aimed to associate the proteomic profiles of metastatic melanoma with the patient clinical information, to identify protein correlates with metastatic location and prior treatments. We performed mass spectrometry-based proteomic analysis of 185 metastatic melanoma samples and followed with bioinformatics analysis to examine the association of metastatic location, status, survival, and immunotherapy response with the tumor molecular profiles. Bioinformatics analysis showed a high degree of functional heterogeneity associated with the site of metastasis. Lung metastases presented higher immune-related proteins, and higher mitochondrial-related processes, which were shown previously to be associated with better immunotherap. These results can be the basis for development of site-specific treatments toward treatment personalization. Diffusion-weighted imaging with the calculation of an apparent diffusion coefficient (ADC) has been proposed as a quantitative biomarker on contrast-enhanced MRI (CE-MRI) of the breast. There is a need to approve a generalizable ADC cutoff. The purpose of this study was to evaluate whether a predefined ADC cutoff allows downgrading of BI-RADS 4 lesions on CE-MRI, avoiding unnecessary biopsies. This was a retrospective, multicentric, cross-sectional study. Data from five centers were pooled on the individual lesion level. Eligible patients had a BI-RADS 4 rating on CE-MRI. this website For each center, two breast radiologists evaluated the images. Data on lesion morphology (mass, non-mass), size, and ADC were collected. Histology was the standard of reference. A previously suggested ADC cutoff (≥1.5 × 10 mm /second) was applied. A negative likelihood ratio of 0.1 or lower was considered as a rule-out criterion for breast cancer. Diagnostic performance indices were calculated by ROC analysis. There were 657 female patients (mean age, 42; SD, 14.1) with 696 BI-RADS 4 lesions included. Disease prevalence was 59.5% (414/696). The area under the ROC curve was 0.784. Applying the investigated ADC cutoff, sensitivity was 96.6% (400/414). The potential reduction of unnecessary biopsies was 32.6% (92/282). An ADC cutoff of ≥1.5 × 10 mm /second allows downgrading of lesions classified as BI-RADS 4 on breast CE-MRI. One-third of unnecessary biopsies could thus be avoided.An ADC cutoff of ≥1.5 × 10-3 mm2/second allows downgrading of lesions classified as BI-RADS 4 on breast CE-MRI. One-third of unnecessary biopsies could thus be avoided. Pembrolizumab demonstrated efficacy in PD-L1-positive [combined positive score (CPS) ≥1] advanced gastric/gastroesophageal junction (G/GEJ) cancer in the first-, second-, and third-line setting in KEYNOTE-062, KEYNOTE-061, and KEYNOTE-059, respectively. To better delineate the specificity of CPS as a predictor of clinical outcomes, we analyzed pembrolizumab efficacy in patients with CPS ≥ 10 in these trials. Included were patients with CPS ≥ 10 tumors from KEYNOTE-059 cohort 1 (pembrolizumab, = 46; ), KEYNOTE-061 (pembrolizumab, = 53; chemotherapy, = 55; ), and KEYNOTE-062 (pembrolizumab, = 92; chemotherapy, = 90; primary). Efficacy outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR). In KEYNOTE-059, median follow-up was 6 months, median OS was 8 months [95% confidence interval (CI), 5.8-11.1], ORR was 17%, and median (range) DOR was 21 months (3+ to 35+). In KEYNOTE-061, median follow-up was 9 months, median OS (pembrolizumab vs. chemotherapy) was 10 versus 8 months (HR, 0.64; 95% CI, 0.41-1.02), median PFS was 3 months versus 3 months (HR, 0.86; 95% CI, 0.56-1.33), ORR was 25% versus 9%, and median (range) DOR was not reached (4 to 26+ months) versus 7 months (3-7). In KEYNOTE-062, median follow-up was 11 months, median OS (pembrolizumab vs. chemotherapy) was 17 months versus 11 months (HR, 0.69; 95% CI, 0.49-0.97), median PFS was 3 months versus 6 months (HR, 1.09, 95% CI; 0.79-1.49), ORR was 25% versus 38%, and median (range) DOR was 19 months (1+ to 34+) versus 7 months (2+ to 30+). This comprehensive analysis showed consistent improvements toward more favorable clinical outcomes with pembrolizumab across lines of therapy in patients with CPS ≥ 10 G/GEJ cancer.This comprehensive analysis showed consistent improvements toward more favorable clinical outcomes with pembrolizumab across lines of therapy in patients with CPS ≥ 10 G/GEJ cancer. Using RNA sequencing, we recently developed the 52-gene-based Oxford classifier of carcinoma of the ovary (Oxford Classic, OxC) for molecular stratification of serous ovarian cancers (SOCs) based on the molecular profiles of their cell of origin in the fallopian tube epithelium. Here, we developed a 52-gene NanoString panel for the OxC to test the robustness of the classifier. We measured the expression of the 52 genes in an independent cohort of prospectively collected SOC samples ( = 150) from a homogenous cohort who were treated with maximal debulking surgery and chemotherapy. We performed data mining of published expression profiles of SOCs and validated the classifier results on tissue arrays comprising 137 SOCs. We found evidence of profound nongenetic heterogeneity in SOCs. Approximately 20% of SOCs were classified as epithelial-to-mesenchymal transition-high (EMT-high) tumors, which were associated with poor survival. This was independent of established prognostic factors, such as tumor stage, tumor grade, and residual disease after surgery (HR, 3.3; = 0.02). Mining expression data of 593 patients revealed a significant association between the EMT scores of tumors and the estimated fraction of alternatively activated macrophages (M2; < 0.0001), suggesting a mechanistic link between immunosuppression and poor prognosis in EMT-high tumors. The OxC-defined EMT-high SOCs carry particularly poor prognosis independent of established clinical parameters. These tumors are associated with high frequency of immunosuppressive macrophages, suggesting a potential therapeutic target to improve clinical outcome.The OxC-defined EMT-high SOCs carry particularly poor prognosis independent of established clinical parameters. These tumors are associated with high frequency of immunosuppressive macrophages, suggesting a potential therapeutic target to improve clinical outcome.