Cancer-associated fibroblast activation predicts progression, metastasis, and prognosis of cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer and the metastatic disease is associated with poor prognosis. Cancer-associated fibroblasts (CAFs) promote progression of cancer, but their role in cSCC is largely unknown. We examined the potential of CAF markers in the assessment of metastasis risk and prognosis of primary cSCC. We utilized multiplexed fluorescence immunohistochemistry for profiling CAF landscape in metastatic and non-metastatic primary human cSCCs, in metastases, and in premalignant epidermal lesions. Quantitative high-resolution image analysis was performed with two separate panels of antibodies for CAF markers and results were correlated with clinical and histopathological parameters including disease-specific mortality. Increased stromal expression of fibroblast activation protein (FAP), α-smooth muscle actin, and secreted protein acidic and rich in cysteine (SPARC) were associated with progression to invasive cSCC. Elevation of FAP and platelet-derived growth factor receptor-ß (PDGFRß) expression was associated with metastasis risk of primary cSCCs. High expression of PDGFRß and periostin correlated with poor prognosis. Multimarker combination defined CAF subset, PDGFRα-/PDGFRß+/FAP+, was associated with invasion and metastasis, and independently predicted poor disease-specific survival. These results identify high PDGFRß expression alone and multimarker combination PDGFRα-/PDGFRß+/FAP+ by CAFs as potential biomarkers for risk of metastasis and poor prognosis.

Both comorbidity and worse performance status are associated with poorer overall survival after external beam radiotherapy for prostate cancer.

BACKGROUND: In this retrospective study, we evaluated the biochemical recurrence rate, metastatic disease progression, and prostate cancer-specific and overall survival in patients curatively treated with external beam radiotherapy (EBRT) for early prostate cancer (PC). We also examined the prognostic effect of comorbidity by Charlson Comorbidity Index (CCI) and overall performance status by Eastern Clinical Oncology Group (ECOG) score. METHODS: A total of 665 men treated between 2008 and 2013 were enrolled from Tampere University Hospital, Finland. Prostate-specific antigen (PSA) tests and hospital records were used to determine the 5-year survival for each aforementioned endpoint using a Kaplan-Meyer estimate. To analyze the impact of the selected prognostic factor, we used a Cox regression model to calculate the corresponding hazard ratio (HR) and 95% confidence interval (CI). RESULTS: With a median follow-up-time of 7.12 years, the 5-year overall survival (OS) after EBRT was 88.9% [86.5 -91.3%], prostate cancer-specific survival (PCSS) was 97.9% [96.7 -99.1%], metastasis-free survival (MFS) 94.8% [93.0 -96.6%] and biochemical recurrence-free survival (BRFS) 88.7% [86.2 -91.2%]. Both CCI (HR = 1.38, [1.25-1.51]) and ECOG score (HR = 1.63, [1.29-2.05]) declined OS, as well as Gleason score and T score (P <  0.05). Gleason score and T grade also associated to worse PCSS, MFS and BRFS. CONCLUSIONS: CCI and ECOG score are useful tools in evaluating the overall life expectancy of the patient after EBRT for PC. T-stage and Gleason score remain still the major prognostic factors.