Search

Background: Alterations in the human epidermal growth factor receptor‐2 (HER2) pathway have been identified in a subset of salivary duct carcinomas. Dual HER2 inhibition with trastuzumab and pertuzumab has superior antitumor efficacy to trastuzumab monotherapy in HER2‐positive breast cancer, yet its efficacy in HER2‐positive salivary duct carcinoma is unknown. Methods: We report 2 cases of exceptional responses of HER2‐positive salivary duct carcinomas to dual HER2 blockade and docetaxel combination and their molecular characteristics. Results: A 54‐year‐old man with recurrent metastatic HER2 expressing salivary duct carcinoma of the parotid gland after definitive concurrent chemoradiation achieved a complete response (CR) after 6 cycles of trastuzumab, pertuzumab, and docetaxel (TPH). A 42‐year‐old woman with HER2‐positive salivary duct carcinoma of the parotid gland with bone and liver metastases had CR with TPH and remains in remission on maintenance trastuzumab and pertuzumab. Conclusion: Dual HER2 blockage resulted in CR in patients with HER expressing salivary duct carcinoma and warrants further evaluation in this patient population. [ABSTRACT FROM AUTHOR]

Background: MET gene amplification and Met protein overexpression may be associated with a poor prognosis. The MET/Met status is typically determined with fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), respectively. Targeted proteomics uses mass spectrometry-based selected reaction monitoring (SRM) to accurately quantitate Met expression. FISH, IHC, and SRM analyses were compared to characterize the prognostic value of MET/Met in gastroesophageal adenocarcinoma (GEC).Methods: Samples from 447 GEC patients were analyzed for MET gene amplification (FISH) and Met protein expression (IHC and SRM). Cox proportional hazards models and Kaplan-Meier estimates were applied to explore relations between Met, overall survival (OS), and clinical/pathological characteristics. Spearman's rank coefficient was used to assess the correlation between parameters.Results: Patients with MET-amplified tumors had worse OS when: the MET/centromere enumeration probe for chromosome 7 FISH ratio was ≥ 2 (hazard ratio [HR], 3.13; 95% confidence interval [CI], 1.84-5.33), the MET gene copy number was ≥5 (HR, 2.51; 95% CI, 1.45-4.34), or ≥ 10% of the cells had ≥15 copies (HR, 4.28; 95% CI, 2.18-8.39). Similar observations were made with Met protein overexpression by IHC (≥1 + intensity in ≥ 25% of the tumor cell membrane: HR, 1.39; 95% CI, 1.04-1.86) or SRM (≥400 amol/μg: HR, 1.76; 95% CI, 1.06-2.90). A significant correlation was observed between MET FISH/Met IHC, MET FISH/Met SRM, and Met IHC/Met SRM; only MET FISH and Met SRM were independent negative prognostic biomarkers in multivariate analyses.Conclusions: MET amplification and overexpression, assessed by multiple methods, were associated with a worse prognosis in univariate analyses. However, only MET amplification by FISH and Met expression by SRM were independent prognostic biomarkers. Compared with IHC, SRM may provide an added benefit for informed decisions about Met-targeted therapy. Cancer 2017;123:1061-70. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Introduction Current methods to determine HER2 (human epidermal growth factor receptor 2) status are affected by reproducibility issues and do not reliably predict benefit from anti-HER2 therapy. Quantitative measurement of HER2 may more accurately identify breast cancer (BC) patients who will respond to anti-HER2 treatments. Methods Using selected reaction monitoring mass spectrometry (SRM-MS), we quantified HER2 protein levels in formalin-fixed, paraffin-embedded (FFPE) tissue samples that had been classified as HER2 0, 1+, 2+ or 3+ by immunohistochemistry (IHC). Receiver operator curve (ROC) analysis was conducted to obtain optimal HER2 protein expression thresholds predictive of HER2 status (by standard IHC or in situ hybridization [ISH]) and of survival benefit after anti-HER2 therapy. Results Absolute HER2 amol/μg levels were significantly correlated with both HER2 IHC and amplification status by ISH (p < 0.0001). A HER2 threshold of 740 amol/μg showed an agreement rate of 94% with IHC and ISH standard HER2 testing (p < 0.0001). Discordant cases (SRM-MS-negative/ISH-positive) showed a characteristic amplification pattern known as double minutes. HER2 levels >2200 amol/μg were significantly associated with longer disease-free survival (DFS) and overall survival (OS) in an adjuvant setting and with longer OS in a metastatic setting. Conclusion Quantitative HER2 measurement by SRM-MS is superior to IHC and ISH in predicting outcome after treatment with anti-HER2 therapy. [ABSTRACT FROM AUTHOR]

The article presents a study which examined synovial proteinase-activated receptor 2 (PAR-2) expression and to determine the effect of a novel PAR-2 antagonist on synovial cytokine production. A monoclonal antibody was used to characterized expression in rheumatoid arthritis (RA) synovium and cultured synovial fibroblasts. Results showed that PAR-2 was up-regulated in RA synovium compared with control synovial tissue from patients with osteoarthritis of seronegative inflammatory arthritis.