Potassium Channels, Non-selective

Oral Oncol

Oral Oncol. treatment for metastatic disease consisted of TCH every 3 weeks for 6 cycles followed by trastuzumab for variable time periods with or without second-line chemotherapy for progression. All patients had fluorescence in situ hybridization testing for HER2/gene amplification. Results. The median duration of follow-up was 27 months (range: 8C48 months). In all, 62% of adjuvant patients (5/8) had no evidence of disease more than 2 years from completion of therapy. All patients with metastatic disease (5/5 patients) responded to treatment with TCH. One patient achieved a complete response and remains with no evidence of disease 52 months after initiation of TCH. The median duration of response was 18 months (range: 8C52 months). Conclusion. HER2/positivity and treatment with trastuzumab correlated well with long-term survival and response in our patients. Based on this data, we propose that HER2/status be examined routinely in all patients with SDCs and the treatment be directed accordingly. expression [5]. HER2/overexpression or amplification is seen in 15%C20% of patients with invasive breast cancers and is considered an adverse prognostic factor [6]. Strong immunohistochemical (IHC) staining for HER2/protein has been identified in 25%C90% of SDCs and is associated with a poor prognosis [3, 5, 7, 8]. SDCs can be IHC 1C3+ for HER2 in the absence of amplification. The discordance between HER2/expression by IHC and fluorescence in situ hybridization (FISH) also has been of concern in SDC [7]. HER2/3+ positive/FISH nonamplified tumors are considered to be false positive in breast cancer. Such false-positive cases have been reported at 3% in breast cancer versus 27%C43% in SDCs [7]. Single-agent trastuzumab (Herceptin; F. Hoffmann-La Roche, Basel, Switzerland) was previously studied in a phase II trial of multiple histologies of advanced salivary gland carcinomas with minimal benefit. One patient with advanced salivary gland cancer had stabilization of disease for 40 weeks [9]. Based on the palliative and adjuvant data for combination activity of trastuzumab in breast cancer, we treated patients with SDC with trastuzumab-based therapy and present the results in this retrospective analysis. Because of the data regarding discordance in IHC expression and FISH positivity, all patients who were IHC 1C3+ were included in the study. Patients and Methods Thirteen patients with SDC who were treated with trastuzumab-based therapy as the first treatment for adjuvant or recurrent metastatic disease between 2005 and 2010 were identified using the pathology and chemotherapy pharmacy database. All patients were initially evaluated at our institution. A detailed physical examination was done and staging scans were reviewed. Histologic confirmation of disease was made before initiating treatment. Data were reviewed under a retrospective protocol approved by the institutional review board. Pathologic Analysis Immunohistochemistry IHC was performed on 4-m tissue sections using the EnVision+ System (Dako, Carpinteria, CA). Briefly, slides were deparaffinized and rehydrated, with endogenous peroxidase activity blocked using 3% hydrogen peroxide in methanol. Antigen retrieval was performed using 10 mM of citrate buffer pH 6.0 (Target Retrieval Solution S1699, Dako) and pressure cooking MMP14 (Biocare Medical, Concord, CA) at 122C (14 and 17 psi) for 45 minutes. The primary antibody for HER2/(SP3 1:100; Labvision, Fremont, CA) was incubated for 40 minutes at room temperature. A EW-7197 Dako polymer secondary antibody system was used and incubated at room temperature for 30 minutes in a humid chamber. 3,3-diaminobenzidine (Sigma Chemical, St. Louis, MO) was used for detection with counterstaining using Mayer hematoxylin. External positive controls were included with each run. Slides were scored by a pathologist at Brigham and Women’s Hospital (J.K.) EW-7197 as positive 3+ (strong complete membrane immunoreactivity in 30% of tumor cells), equivocal 2+ (weak to moderate complete membrane immunoreactivity in at least 10% of tumor cells), negative 1+ (faint, weak partial membrane immunoreactivity in at least 10% of tumor cells), or negative 0 (no immunoreactivity or immunoreactivity in 10% of EW-7197 tumor cells) according to guidelines from the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) [10]. Fluorescence In Situ Hybridization Bacterial artificial chromosome clones RP11C62N23, RP11C1065L22, and RP11C1044P23 were obtained from Children’s Hospital (Oakland, CA) and used in construction of FISH probes for a 340-kb region including ERBB2. Probes were labeled with biotin using the Random Prime DNA Labeling System (Invitrogen, Grand Island, NY) according to the manufacturer’s protocol and detected with rhodamine (red). A probe to the chromosome 17 centromeric region labeled with fluorescein isothiocyanate was purchased from Abbott Laboratories (Des Plaines, IL)/Vysis Corp (Downers Grove, IL). Specificity of probe binding was verified using normal lymphocyte metaphase spreads. Dual-color FISH was performed on 4-m tissue.