The Potential Clinical Implications of Circulating Tumor Cells and Circulating Tumor Microemboli in Gastric Cancer.

BACKGROUND: Gastric adenocarcinoma (GAC) is the third deadliest malignant neoplasm worldwide, mostly because of late disease diagnosis, low chemotherapy response rates, and an overall lack of tumor biology understanding. Therefore, tools for prognosis and prediction of treatment response are needed. Quantification of circulating tumor cells (CTCs) and circulating tumor microemboli (CTM) and their expression of biomarkers has potential clinical relevance. Our aim was to evaluate CTCs and CTM and their expression of HER2 and plakoglobin in patients with nonmetastatic GAC, correlating the findings to clinicopathological data. MATERIALS AND METHODS: CTC enrichment was performed with isolation by size of epithelial tumor cells, and the analysis was performed with immunocytochemistry and microscopy. Two collections were made: one at diagnosis (55 samples before neoadjuvant treatment) and one after surgery and before adjuvant therapy (33 samples). RESULTS: A high detection rate of CTCs (90%) was observed at baseline. We evaluated HER2 expression in 45/55 biopsy samples and in 42/55 CTC samples, with an overlap of 36 subjects. Besides the good agreement observed for HER2 expression in primary tumors and paired CTCs for 36 cases (69.4%; κ = 0.272), the analysis of HER2 in CTCs showed higher positivity (43%) compared with primary tumors (11%); 3/5 patients with disease progression had HER2-negative primary tumors but HER2-positive CTCs. A significant CTC count drop in follow-up was seen for CTC-HER2-positive cases (4.45 to 1.0 CTCs per mL) compared with CTC-HER2-negative cases (2.6 to 1.0 CTCs per mL). The same was observed for CTC-plakoglobin-positive cases (2.9 to 1.25 CTCs per mL). CONCLUSION: CTC analysis, including their levels, plakoglobin, and HER2 expression, appears to be a promising tool in the understanding the biology and prognosis of GAC. IMPLICATIONS FOR PRACTICE: The analysis of circulating tumor cell levels from the blood of patients with gastric adenocarcinoma, before and after neoadjuvant treatment, is useful to better understand the behavior of the disease as well as the patients more likely to respond to treatment.

Epidemiological Profile and Treatment Outcomes in Young Adults (19-29 Years of Age) Treated for Cancer in a Tertiary Hospital in São Paulo, Brazil.

BACKGROUND: Worldwide, the incidence of cancer in young adults (20-39 years) is increasing, and represents an important cause of mortality in this age group. A retrospective study was undertaken to provide information that may lead to improved treatment outcomes. METHODS: Epidemiological, clinicopathological, treatment, and survival information were retrieved from the electronic database registry of a tertiary referral hospital in São Paulo, Brazil for patients 19-29 years of age diagnosed with cancer between January 2007 and December 2012. RESULTS: There were 960 patients with a median age at diagnosis of 26 years; female patients comprised 59.2%. A previous diagnosis of malignancy was present in 2.3%; 0.4% had malignant tumors that were radiation-associated; regular alcohol use was present in 10.4%; 9% of patients reported tobacco use; a family history of cancer was present in 41.7%. Malignant tumors included carcinomas (45.7%), germ cell and trophoblastic neoplasms (12.3%), and lymphomas (12.1%). Median follow-up was 47.7 months (range: 0.62-100.9 months) during which time 111 patients (13.5%) died. Carcinomas (n = 43, 38.7%), soft tissue sarcomas (n = 18, 16.2%), and leukemias (n = 10, 9.0%) were the most common causes of death. CONCLUSIONS: This study has shown that carcinomas represent the most common malignancy in adolescents and young adults referred to a tertiary cancer center in Brazil and are the most common cause of mortality. Because clinical outcome may be affected by multiple factors in this patient population, further global studies are needed to characterize this population and improve clinical care.

Circulating tumor cells as a new and additional approach to follow-up patients with serous low-grade ovarian adenocarcinoma: a case report and review of the literature

Background: Current methods for follow-up of Ovarian Cancer (OC) are widespread, especially with CA125, which, however, is not a perfect biomarker and thus further investigation for new methods of evaluation are warranted. The feasibility of Circulating Tumor Cells (CTCs) in advanced OC was investigated in this case report. Case presentation: A 19-year-old woman with advanced low-grade serous papillary adenocarcinoma and relapsed disease did not have a CA125 correspondent with disease relapse. CTCs were evaluated, compared with CA125 and with image exams. Relapses were not correspondent to elevations of CA125. CTCs demonstrated usefulness, being proportional to major disease relapse, especially in the peritoneum. CTCs may be used as a complementary diagnosis tool when marginal/small increases in CA-125 levels are observed. Conclusions: In OC, CTCs can be an important tool to predict recurrence, response to treatment and improve the quality of decision-making, in order to offer the best treatment to a determined group of patients (AU)

Isolation, detection, and immunomorphological characterization of circulating tumor cells (CTCs) from patients with different types of sarcoma using isolation by size of tumor cells: a window on sarcoma-cell invasion.

BACKGROUND: Sarcomas are rare and heterogeneous neoplasms with poor prognosis that are thought to spread to distant organs mainly by hematogenous dissemination. However, circulating tumor cells (CTCs) have never been visualized in sarcomas. OBJECTIVES: To investigate the feasibility of using isolation by size of tumor cells (ISET) for isolation, identification, and characterization of CTCs derived from patients with high-grade and metastatic sarcomas. PATIENTS AND METHODS: We studied eleven patients with metastatic/recurrent or locally advanced soft-tissue sarcomas (STSs), six of whom had synovial sarcomas. Blood samples (8 mL) were collected from patients with advanced STS and treated by ISET, a marker- independent approach that isolates intact CTCs from blood, based on their larger size compared with leukocytes. CTCs were identified by cytomorphology and characterized by dual-color immunocytochemistry using antivimentin or anti-Pan CK, and anti-CD45. RESULTS: All patients with STS included in this study showed CTCs, with numbers ranging from two to 48 per 8 mL of blood. CONCLUSION: This study shows the feasibility of isolating, identifying, and characterizing CTCs from patients with different types of sarcomas and the presence of circulating sarcoma cells in all the tested patients. Our results set the basis for further studies aimed at exploring the presence, number, and immunomolecular characteristics of CTCs in different types of sarcoma, and bring more light to the mechanisms of tumor invasion for these tumors.

The influence of transforming growth factor-α, cyclooxygenase-2, matrix metalloproteinase (MMP)-7, MMP-9 and CXCR4 proteins involved in epithelial-mesenchymal transition on overall survival of patients with gastric cancer.

AIMS: Determination of prognostic parameters that are predictive of survival of gastric cancer (GC) may allow better identification of patients who could benefit from current chemotherapy regimens. To assess the correlation between tumour progression and epithelial-mesenchymal transition (EMT), we assayed the expression levels of selected molecules involved in EMT [CD44, transforming growth factor (TGF)-α, cyclooxygenase-2 (COX-2), matrix metalloproteinase (MMP)-7, MMP-9 and C-X-C chemokine receptor (CXCR4)], and correlated these with overall patient survival (OS) and disease stage. METHODS AND RESULTS: Medical records and pathological biopsy results of 137 patients with GC were evaluated retrospectively. Spearman's correlation analysis showed that expression of CXCR4 was correlated significantly with the expression of all other proteins studied. In contrast, COX-2 expression correlated significantly with the expression of only MMP-7 (P = 0.011), MMP-9 (P = 0.015) and CXCR4 (P = 0.013). We observed significant negative correlations between OS and the expression of TGF-α (P = 0.017), COX-2 (P < 0.001), CXCR4 (P = 0.010), MMP-7 (P = 0.020) and MMP-9 (P = 0.015). On multivariate analysis, only COX-2 was an independent prognostic factor for OS [hazard ratio (HR) = 3.34; 95% confidence interval (CI): 1.43-9.75; P = 0.002). CONCLUSIONS: COX-2, TGF-α, MMP-7, MMP-9 and CXCR4 are associated with poor OS in gastric cancer.