Circulating tumor cells (CTC) in blood are associated with poor survival of patients with breast, prostate, or colon cancer. We hypothesized that CTC are associated with poor survival of patients with cholangiocarcinoma (CCA). 88 patients with CCA were prospectively enrolled at Mayo Clinic Rochester between June 2010 and September 2014. The CellSearch system by Veridex was used for detection of CTC in peripheral blood. Associations between CTC, patient and tumor characteristics and survival were examined using the Cox proportional hazards model. Fifteen patients (17%) were positive for CTC ≥2 and 8 patients (9%) for CTC ≥5. CTC were associated with tumor extent. CTC ≥2 (HR, 2.5; 95%CI, 1.1–5.4; p=0.02) and CTC ≥5 (HR, 4.1; 95%CI, 1.4–10.8; p=0.01) were both independent predictors of survival. In subgroup analyses, CTC ≥2 (HR 8.2; 95%CI 1.8–57.5; p<0.01) and CTC ≥5 (HR 7.7; 95%CI 1.4–42.9; p=0.02) were both associated with shorter survival among patients with metastasis. There was a trend towards association of CTC ≥5 with shorter survival in patients with non-metastatic CCA (HR 4.3; 95%CI 1.0–13.8; p=0.06). CTC ≥2 (10.5; 95%CI 2.2–40.1; p<0.01) and CTC ≥5 (HR 10.2; 95%CI 1.5–42.3; p=0.02) were both associated with shorter survival among patients with perihilar/distal CCA. CTC ≥5 was associated with shorter survival of patients with intrahepatic CCA (HR 4.2; 95%CI 1.1–14.1; p=0.04). Conclusion CTC were associated with more aggressive tumor characteristics and independently associated with survival in patients with CCA. Assessment of CTC may be useful for identifying CCA patients at risk of early mortality.
SummaryNew detection methods with prognostic power are needed for early identification of dysplasia and esophageal adenocarcinoma (EA) in patients with Barrett's esophagus (BE). This study assessed the relative sensitivity and specificity of conventional cytology, DNA ploidy analysis with digital image analysis (DIA), and fluorescence in situ hybridization (FISH) for the detection of dysplasia and adenocarcinoma in endoscopic brushing specimens from 92 patients undergoing endoscopic surveillance for BE. FISH used probes to 8q24 (C-MYC), 9p21 (P16), 17q12 (HER2), and 20q13. Four-quadrant biopsies taken every centimeter throughout visible Barrett's mucosa were used as the gold standard. The sensitivity of cytology, DIA, and FISH for low-grade dysplasia was 5%, 5%, and 50%, respectively; for high-grade dysplasia (HGD), 32%, 45%, and 82%, respectively; and for EA, 45%, 45%, and 100%, respectively. FISH was more sensitive (P < .05) than cytology and DIA for low-grade dysplasia, HGD, and EA. The specificity of cytology, DIA, and FISH among patients (n = 14) with tissue showing only benign squamous mucosa was 93%, 86%, and 100% (P = .22), respectively. All patients with a polysomic FISH result had HGD and/or EA within 6 months (n = 33). There was a significant difference between FISH categories (negative, 9p21 loss, gain of a single locus, and polysomy) for progression to HGD/EA (P < .001). These findings suggest that FISH has high sensitivity for the detection of dysplasia and EA in BE patients, with the power to stratify patients by FISH abnormality for progression to HGD/EA. Additional studies are needed to further evaluate the clinical use of FISH.
BACKGROUND. Endometrial cytology sampling devices for direct uterine sampling have been shown in previous studies to be a reliable and relatively painless method for detecting endometrial lesions. The purpose of the current study was to determine the performance characteristics of endometrial cytology for the detection of malignancy and atypical hyperplasia using liquid‐based cytology specimens collected with the Tao brush sampler. METHODS. Brushings of the endometrial cavity were obtained from 139 hysterectomy specimens before routine histopathologic evaluation. Cytology specimens were fixed in PreservCyt and processed using ThinPrep technology. Cytology diagnoses were classified as nondiagnostic, negative, atypical, or positive for malignancy. Histopathologic findings were used as the gold standard for determining the performance characteristics of cytology. RESULTS. Histopathologic results from the 139 patients included 81 (58%) endometrial cancers, 7 (5%) complex hyperplasias with atypia, 2 (1%) complex hyperplasias without atypia, and 49 (35%) patients with benign histology. The number of specimens diagnosed cytologically as positive, atypical, negative, or nondiagnostic was 60 (43%), 40 (29%), 37 (27%), and 2 (1%) specimens, respectively. The overall sensitivity and specificity of cytology for detecting endometrial cancer and atypical hyperplasia were 95% and 66% when atypical cytology specimens were considered positive. CONCLUSIONS. The results of the current study indicate that direct endometrial sampling by liquid‐based endometrial cytology collected with the Tao brush sampler produces specimens that contain cellular material that may be identified as endometrial cancer or atypical hyperplasia. Both atypical and positive cytology diagnoses are indicators for triage to more specific methods of diagnosis. Cancer (Cancer Cytopathol) 2008. © 2008 American Cancer Society
BACKGROUND: Multigene molecular testing to guide personalized therapy for oncology patients is of increasing clinical relevance. Molecular testing of fine-needle aspiration samples is underused, but when acquired with minimally invasive techniques could become the standard of care to obtain theranostic specimens. The aims of the current study were to identify key cytology specimen selection criteria suitable for next-generation sequencing (NGS) and to determine the prevalence and spectrum of pathogenic alterations in a cohort of patients with AJCC stage IV lung cancer. METHODS: A total of 70 adrenal gland cytology specimens with direct smears were screened to identify 56 patients with a single slide containing at least 300 total cells and 20% tumor nuclei. After DNA extraction, the NGS protocols were used to simultaneously detect mutations in >2800 exonic regions in 50 key cancer genes. RESULTS: A total of 28 specimens produced acceptable NGS results. Specimens with a combined critical cell mass (>5000 viable cells) and a DNA concentration >5 ng/mL resulted in a 95% chance of successful sequencing. A total of 37 pathogenic alterations were identified in 10 genes and in 25 patients (85%). A pathogenic alteration ( 1) linked to available or developing targeted therapies was revealed in 50% of cases. CONCLUSIONS: The data from the current study demonstrate that theranostic NGS can be applied to adrenal gland metastasis using routine cytologic smear specimens. The characteristics of such smears could be evaluated during onsite adequacy assessment by cytopathology professionals. This model greatly augments the opportunity for customized genotype-directed therapy from minimally invasive techniques. Cancer (Cancer Cytopathol) 2014;122:822-32.
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