Linda Zinoli

Periostin: A Novel Prognostic and Therapeutic Target For Genitourinary Cancer?

Many of the cellular abnormalities present in solid tumors are structural in nature and involve the proteins of the extracellular matrix (ECM). Periostin is a protein produced and secreted by the fibroblasts as a component of the ECM where it is involved in regulating intercellular adhesion. The expression of periostin has an important physiological role during embryogenesis and growth, namely at the level of bone, dental, and cardiac tissues. Many studies indicate that periostin plays an important role for tumor progression in various types of cancer, such as colon, lung, head and neck, breast, ovarian, and prostate. To the best of our knowledge, a limited number of studies have investigated periostin expression in urogenital cancer, such as prostate, bladder, penile, and renal cancer, and no studies were performed in testis cancer. In this review article, we summarize the most recent knowledge of periostin, its genetic and protein structure, and the role of the different isoforms identified and sequenced so far. In particular, we focus our attention on the role of this protein in genitourinary tumors, trying to emphasize the role not only as a possible prognostic marker, but also as a possible target for the development of future anticancer therapies.

Prognostic Value of Preoperative Serum Levels of Periostin (PN) in Early Breast Cancer (BCa).

PN is a secreted cell adhesion protein critical for carcinogenesis. Elevated serum levels of PN have been implicated as playing an important role in different types of cancer, and a few reports suggest a potential role as a prognostic marker. We evaluated the prognostic significance of preoperative serum PN concentration in patients with BCa receiving curative surgery. Enzyme-Linked Immunosorbent Assay (ELISA) was performed to determine the preoperative serum PN level in 182 patients. The correlations between serum PN concentration with clinical pathological features and PN expression in primary tumor samples were analyzed. The prognostic impact of serum PN levels with all-cause and BCa-specific mortality was also investigated. Appropriate statistics were used. Elevated serum PN levels were significantly associated with patient age (p = 0.005), adjuvant systemic therapy (p = 0.04) and progesterone receptor (PgR) status (p = 0.02). No correlation between PN preoperative serum levels and other clinical-pathological parameters, including either the epithelial or the stromal PN expression of primary tumor or the combination of the two, was found. Similarly, no association between serum PN levels and either all-cause or BCa-specific mortality was found. However, subgroup analysis revealed a correlation between higher PN serum levels and all-cause mortality in patients with node-negative disease (p = 0.05) and in those with a low PgR expression (p = 0.03). Higher levels of serum PN were also found to correlate with BCa-specific mortality in the subgroup of patients who did not receive any adjuvant systemic therapy (p = 0.04). Our findings suggest that PN was detectable in the serum of early BCa patients before surgery and increased base-line serum levels predicted worse long-term survival outcomes in specific subgroups of patients.

Abiraterone acetate and prednisone in the pre- and post-docetaxel setting for metastatic castration-resistant prostate cancer: A mono-institutional experience focused on cardiovascular events and their impact on clinical outcomes

Background: The aim of this work was to to evaluate the incidence and risk factors of adverse events (AEs), focusing on cardiovascular events (CVEs) and hypokalemia, in patients treated with abiraterone acetate (AA) and prednisone (PDN) outside clinical trials, and their association with survival outcomes. Methods: This was a retrospective cohort study of 105 patients treated from 2011 to 2016. Incidence of AEs was descriptively summarized in the whole cohort and by subgroup (pre- versus post-docetaxel). Multivariable Cox proportional hazards models assessed factors associated with progression-free survival (PFS) and overall survival (OS). Results: Overall, median PFS and OS were 14.9 and 24.6 months, respectively. Prostate-specific antigen (PSA) ⩾ 10 ng/ml (p = 0.007), Gleason Score >7 (p = 0.008), Eastern Cooperative Oncology Group (ECOG) performance status (PS)1–2 (p = 0.002), duration of androgen deprivation therapy (ADT) ⩽ 43.2 months (p = 0.01), and body mass index (BMI) > 25 (p = 0.03) were associated with worse PFS; presence of pain (p = 0.01), ECOG PS1–2 (p = 0.004), duration of ADT ⩽ 43.2 (p = 0.05), and BMI > 25 (p = 0.042) were associated with worse OS. Incidence of CVEs was as follows: hypertension 17.1%, fluid retention 4.8%, cardiac disorders 8.6%. 16.2% of patients developed hypokalemia. Age ⩾ 75 years was associated with higher probability of cardiac disorders (p = 0.001) and fluid retention (p = 0.03). CVEs did not impact on PFS or OS. Hypokalemia was associated with better median OS (p = 0.036). Similar associations were observed after stratification by subgroup. Conclusions: Median PFS and OS estimates and incidence of CVEs and hypokalemia in our series are consistent with those of pivotal trials of AA plus PDN, confirming the efficacy and safety of this regimen also in the real-world setting. Elderly patients have higher odds of developing/worsening CVEs. However, regardless of age, CVEs were not associated with worse outcomes. Treatment-related hypokalemia seemed to be associated with longer OS, albeit this finding needs confirmation within larger, prospective series.

Overexpression of Periostin in Tumor Biopsy Samples Is Associated With Prostate Cancer Phenotype and Clinical Outcome

Background: Overexpression of periostin (POSTN) is associated with prostate cancer (PCa) aggressiveness. We investigated the prognostic significance of POSTN expression in tumor biopsy samples of patients with PCa. Methods: We scored POSTN expression by immunohistochemistry analysis on 215 PCa biopsy samples using an anti–POSTN‐specific antibody. A total immunoreactive score (T‐IRS) was calculated by adding the POSTN staining scores of stromal and epithelial tumor cells. Prostate‐specific antigen (PSA) progression/recurrence‐free survival (PFS), radiographic progression/recurrence‐free survival (rPFS), and overall survival (OS) were the study end points. Results: A total of 143 patients received therapy with radical attempt, whereas 72 had locally advanced or metastatic disease and received hormone therapy alone. Median T‐IRS was 9 and 12 (range, 0‐20), respectively (P = .001). Overall, we found a weak positive correlation of T‐IRS with prebiopsy PSA levels (r = 0.166, P = .016) and Gleason score (r = 0.266, P < .000). T‐IRS ≥ 8 independently predicted for shorter PSA‐PFS and OS (hazard ratio [HR] [95% confidence interval (CI)] ≥ 8 versus < 8: 1.50 [1.06‐2.14], P = .024 and 1.92 [1.20‐3.07], P = .007, respectively). In the subgroup analysis, the association between T‐IRS and patient outcome was retained in patients who received therapy with radical attempt (HR [95% CI] ≥ 8 vs. < 8: rPFS: 2.06 [1.18‐3.58], P = .01; OS: 2.36 [1.24‐4.50], P = .009) and in those with low to intermediate Gleason scores (HR [95% CI] ≥ 8 vs. < 8: PSA‐PFS: 1.65 [1.06‐2.59], P = .028; rPFS: 2.09 [1.14‐3.87], P = .018; OS: 2.57 [1.31‐5.04], P = .006). Conclusion: POSTN T‐IRS on PCa biopsy samples independently predicted the risk of recurrence, progression, and death in patients with localized disease and in those with low to intermediate Gleason scores.