Presence Of Metastases In Patients Research Articles

THE EFFECTS OF CANCER’S METASTATIC STATUS AND CHEMOTHERAPY ON TOTALLY IMPLANTABLE VENOUS ACCESS PORT PATENCY AND PORT-RELATED VENOUS THROMBOEMBOLIC EVENTS

Objective: Totally implantable venous access port (TIVAP) is of great importance as a vascular access route in the treatment of cancer patients. In this study, we retrospectively researched the effects of cancer types, metastases, chemotherapeutic drugs, and intervention sites on port patency and TIVAP-related venous thromboembolism (VTE).
 Method: Demographics, cancer types, metastases, vascular access sites, chemotherapy drugs, TIVAP patency and TIVAP related complications were evaluated in 297 patients who had TIVAP implanted and 37 patients who underwent removal in our clinic between 2017-2021.
 Results: TIVAP implanted 297 patients were followed-up for a mean 17.7±16.6 months. TIVAPs were removed in 37 patients due to infection 14 (4.7%), occlusion 8 (2.7%), VTE 9 (3%), malposition 1 (0.3%), and treatment completion 10 (3.3%). TIVAPs of 270 (90.9%) patients were found to be usable for an average of 18.5±17.1 months. Complications of VTE, occlusion, infection and malposition developed in a total of 71 (23.9%) patients. In the comparison of develepment of these complications according to the presence of metastasis in patients, it was found to be that they were significantly higher in metastatic patients (47-27.9%/24-18.6%, p

Expression of Breast Cancer Gene 2 in Oral Squamous Cell Carcinoma and its Correlation with the Metastatic Potential

Background: Breast cancer gene 2 (BRCA2), a tumor suppressor gene, has been extensively evaluated in various cancers and correlated with metastatic potentials. However, to the best of our knowledge, the correlation has not been reflected in the literature in patients with oral squamous cell carcinoma (OSCC). Any positive correlation may yield the protein as an exploitable marker for the prediction of metastasis and target for chemotherapy in patients with OSCC. Materials and Methods: This observational retrospective study was conducted on 54 tissue samples, 18 samples each of normal oral mucosa, and of OSCC with and without cervical lymph node metastasis. The study samples were immunohistochemically stained with BRCA2 antibody. The staining index was calculated as a product of the percentage of positive cells per high-power field (HPF) (A) and the staining intensity (B). Results: Based on intergroup comparisons, it was found that the percentage of positive cells/HPF, staining intensity, and staining index were higher in OSCCs with cervical lymph node metastasis and lower in normal oral mucosa samples. It was found that a large number of the normal oral mucosa samples (n = 13) did not show any BRCA2 immunoreactivity and a large number of the OSCC samples with cervical lymph node metastasis displayed high BRCA2 immunoreactivity (n = 15). Conclusion: Overexpression of BRCA2 is linked to the presence of metastases in patients with OSCC and has the potential to be utilised as a marker to predict the outcome of the patient's treatment. The findings may be used in the future to develop targeted therapies, depending on the direction that future research follows.

Semaphorin-3F/Neuropilin-2 Transcriptional Expression as a Predictive Biomarker of Occult Lymph Node Metastases in HNSCC

Simple SummaryThe presence of lymph neck node metastasis is the most important clinical prognostic factor in patients with head and neck squamous cell carcinoma. The expression of the semaphorin-3F and neuropilin-2 proteins is involved in the regulation of lymphangiogenesis. We analized the transcriptional expression of semaphorin-3F and neuropilin-2 in head and neck squamous cell carcinoma tumors of patients without clinical or radiology evidence of lymph node involvement treated with elective neck dissection. We found that patients with high semaphorin-3F and low neuropilin-2 had a lower risk of occult lymph node metastasis than the ones who had low semaphorin-3F or high semaphorin-3F and high neuropilin-2. If our results are validated, the expression of the SEMA3F-NRP2 axis could be used as a biomarker predicting the risk of occult lymph node metastasis, with elective neck dissections being indicated exclusively for patients at higher risk. The availability of a biomarker with the capacity to predict the presence of occult lymph node metastases would make it possible to avoid elective neck dissections in low-risk patients, with the consequent decrease in surgical time and morbidity of the treatment without impairing the oncologic outcome.The expression of the semaphorin-3F (SEMA3F) and neuropilin-2 (NRP2) is involved in the regulation of lymphangiogenesis. The present study analyzes the relationship between the transcriptional expression of the SEMA3F-NRP2 genes and the presence of occult lymph node metastases in patients with cN0 head and neck squamous cell carcinomas. We analyzed the transcriptional expression of SEMA3F and NRP2 in a cohort of 53 patients with cN0 squamous cell carcinoma treated with an elective neck dissection. Occult lymph node metastases were found in 37.7% of the patients. Patients with occult lymph node metastases (cN0/pN+) had significantly lower SEMA3F expression values than patients without lymph node involvement (cN0/pN0). Considering the expression of the SEMA3F-NRP2 genes, patients were classified into two groups according to the risk of occult nodal metastasis: Group 1 (n = 34), high SEMA3F/low NRP2 expression, with a low risk of occult nodal involvement (14.7% cN0/pN+); Group 2 (n = 19), low SEMA3F or high SEMA3F/high NRP2 expression, with a high risk of occult nodal involvement (78.9% cN0/pN+). Multivariate analysis showed that patients in Group 2 had a 26.2 higher risk of lymph node involvement than patients in Group 1. There was a significant relationship between the transcriptional expression values of the SEMA3F-NRP2 genes and the risk of occult nodal metastases.

Molecular genetic predictors of metastatic lesions of regional lymph nodes in patients with breast cancer

Objective: to identify molecular genetic predictors of metastatic spread to regional lymph nodes in patients with breast cancer (BC) based on the analysis of gene expression profile of the primary tumor.Materials and methods. The study included 358 patients with BC who underwent surgical treatment in breast cancer department of Academician V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia. Among all included into the study patients, 132 (36.9 %) had metastases in at least one axillary lymph node. Molecular genetic examination of the tumor tissue was carried out using reverse transcription polymerase chain reaction; the diagnostic panel consisted of 45 functional and 3 reference genes. Results. Patients with metastases to regional lymph nodes were generally younger (p = 0.006), had larger primary tumor (p<0.001) and higher total malignancy score (p<0.001). The groups were also significantly different in tumor location (p = 0.005). Comparative analysis of transcriptome tumor profiling revealed statistically significant differences between groups in the level of expression of three genes: TMEM45A (p = 0.016), CCND1 (p = 0.019), and MIA (p = 0.046). Based on the data obtained we used mathematical modeling and created a predictive model, which with a high degree of probability (AUC = 0.791) allowed to predict the presence of regional lymph nodes metastases in patients with BC.Conclusion. TMEM45A, CCND1 and MIA gene expression in the primary tumor were the markers of lymph node involvement in BC. The developed predictive genetic signature can become an additional diagnostic tool to predict the risk of lymph node metastases at the point of planning the volume of axillary surgery in patients with BC.

Остеопонтин та остеокальцин при раку легенів

Актуальність. Рак легенів (РЛ) займає лідуючу позицію в структурі онкологічної захворюваності та є однією з провідних причин смерті від онкозахворювань. Пошук ефективних підходів до оцінки перебігу РЛ з використанням інформативних критеріїв є актуальним завданням сучасної онкології. РЛ зазвичай перебігає з підвищеним рівнем у крові остеопонтину (ОР) та остеокальцину (ОС), що має прогностичну значущість у рамках виживання хворих. Сироватковий вміст цих остеоонкомаркерів прямо асоціюється з наявністю у хворих метастазів і з високими темпами прогресування захворювання, але ці дані вимагають подальшого уточнення. Мета дослідження: оцінити клініко-патогенетичну й прогностичну значущість ОР та ОС у хворих із різними варіантами перебігу РЛ. Матеріали та методи. Обстежено 115 хворих на РЛ віком від 24 до 80 років (у середньому 58 років), серед яких було 78 % чоловіків і 22 % жінок. Жоден пацієнт раніше не був прооперований із приводу РЛ і до обстеження не отримував радіохіміотерапію. Дрібноклітинний гістологічний варіант РЛ встановлений у 17 % від числа хворих, недрібноклітинний — у 83 %. Імуноферментним аналізом вивчали в сироватці крові показники ОР, ОС і судинного ендотеліального фактору росту (VEGF). Результати. У хворих на РЛ збільшуються в сироватці крові показники онкоостеоасоційованих маркерів OP та OC, що спостерігається відповідно в 99 і 98 % випадків. Зміни ОР і ОС пов’язані з формою захворювання, гістологічним його варіантом, ступенем диференціації, інтегральною тяжкістю перебігу РЛ, характером ускладнень первинної пухлини й особливостями метастазування. Високий рівень маркерів у крові мало впливає на трирічне виживання пацієнтів, а прогнознегативними критеріями відносно перебігу РЛ є параметри ОР. Показники ОР і ОС у крові між собою прямо корелюють, а вміст ОР, окрім того, має позитивні співвідношення з таким пухлинним маркером, як VEGF, що належить до стимуляторів неоангіогенезу. Метастатичне ураження скелету й розвиток порушень мозкового кровообігу внаслідок подальшої радіохіміотерапії прямо пов’язані з високою концентрацією в крові ОР, який також є чинником ризику інших ускладнень лікування. Висновки. Підвищені рівні в крові ОР і ОС мають важливе клініко-патогенетичне значення при РЛ, а вивчення показників цих остеоонкомаркерів сприятиме ранній діагностиці окремих ознак перебігу захворювання, підвищенню якості оцінки метастазування в кістково-суглобовий апарат і прогнозуванню можливих ускладнень радіохіміотерапії.

The Predictive Value of Proportional Evaluation Based on the Metabolic Activity of Cervical Lymph Nodes on PET/CT Imaging in Patients with Larynx Cancer.

Objectives:We aimed to evaluate the proportional values of maximum standardized uptake value (SUVmax) for cervical lymph nodes on 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for prediction of the presence of metastasis in patients with larynx squamous cell cancer (LSCC).Methods:This retrospective study involved 43 patients with LSCC. All patients underwent resection of the primary tumor and neck dissection within 4 weeks after undergoing 18F-FDG PET/CT examinations. Receiver operating characteristic (ROC) analysis was performed to evaluate the lymph node SUVmax/primary tumor SUVmax (SUVmaxLN/SUVmaxPT), lymph node SUVmax/aortic SUVmax (SUVmaxLN/SUVmaxA), and lymph node SUVmax/liver SUVmax (SUVmaxLN/ SUVmaxL) ratios for diagnosis of lymph node metastasis.Results:SUVmaxLN/SUVmaxA, SUVmaxLN/SUVmaxL, and SUVmaxLN/SUVmaxPT rates were significantly higher in metastatic lymph nodes compared to non-metastatic nodes. ROC analysis for metastasis showed that the cut-off thresholds were 3.87 for SUVmaxLN; 1.78 for SUVmaxLN /SUVmaxA; 1.08 for SUVmaxLN/SUVmaxL; and 0.36 for SUVmaxLN/SUVmaxPT. The diagnostic sensitivity, specificity and AUC were 83.7%, 77%, 0.856 for SUVmaxLN; 79.7%, 84%, 1.78 for SUVmaxLN/SUVmaxA; 84.1%, 76%, 0.833 for SUVmaxLN/SUVmaxL; and 53.6%, 76%, 0.666 for SUVmaxLN/SUVmaxPT, respectively.Conclusion:SUVmaxLN/SUVmaxA, SUVmaxLN/SUVmaxL, and SUVmaxLN/SUVmaxPT ratios can be safely used for diagnosis of cervical lymph node metastasis in patients with LSCC.

Case report of oxalate nephropathy in a patient with pancreatic metastases from renal carcinoma

BackgroundPatients with metastatic renal carcinoma frequently have pre-existing renal impairment and not infrequently develop worsening renal function as a complication of their treatment. The presence of pancreatic metastases in patients with metastatic renal carcinoma, often confers a more favourable prognosis and as a consequence this patient group may be exposed to such treatments for more prolonged periods of time. However, the development of renal failure may also be a consequence of the cancer itself rather than its treatment.Case presentationWe present an 84-year-old patient receiving the tyrosine kinase inhibitor (TKI) pazopanib for metastatic renal carcinoma who developed oxalate nephropathy as a consequence of pancreatic exocrine insufficiency resulting from pancreatic metastases.ConclusionsThis case demonstrates the importance of investigating unexpected toxicities and highlights the potential consequences of pancreatic insufficiency and its sequelae in patients with pancreatic metastases.

Down-Regulation of Cannabinoid Type 1 (CB1) Receptor and its Downstream Signaling Pathways in Metastatic Colorectal Cancer.

Changes in the regulation of endocannabinoid production, together with an altered expression of their receptors are hallmarks of cancer, including colorectal cancer (CRC). Although several studies have been conducted to understand the biological role of the CB1 receptor in cancer, little is known about its involvement in the metastatic process of CRC. The aim of this study was to investigate the possible link between CB1 receptor expression and the presence of metastasis in patients with CRC, investigating the main signaling pathways elicited downstream of CB1 receptor in colon cancer. Fifty-nine consecutive patients, with histologically proven colorectal cancer, were enrolled in the study, of which 30 patients with synchronous metastasis, at first diagnosis and 29 without metastasis. A low expression of CB1 receptor were detected in primary tumor tissue of CRC patients with metastasis and consequently, we observed an alteration of CB1 receptor downstream signaling. These signaling routes were also altered in intestinal normal mucosa, suggesting that, normal mucosa surrounding the tumor provides a realistic picture of the molecules involved in tissue malignant transformation. These observations contribute to the idea that drugs able to induce CB1 receptor expression can be helpful in order to set new anticancer therapeutic strategies.

Is there a Correlation between Metabolic Activity of the Primary Tumor with the Presence of Liver Metastases in Patients with Lung Cancer?

Background: Liver metastasis signal poor prognosis and survival in patients with lung cancer. To better understand tumor behavior, we aimed to determine if there is any correlation between primary tumor features with the features of liver metastasis on F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) images.

Lung cancer diagnosed by a metastatic lesion in the mandible

Introduction Lung cancer is the second most common cancer in the UK accounting for 13% of all new cases. It is the second most common cancer in both males and females. Lung (12.6%) is the second most common primary to metastasis to the jawbones preceded by breast (21.8%). Distant metastasis are present in the late stages of the disease. It is reported that the prognosis following presentation of oral metastasis is poor with the mean survival time 7.3 months. Bony metastases are rarely asymptomatic and in 2.3% of cases the bone metastasis is the initial presenting complaint as presented here. Case description 61-year-old female presented to AE the results indicated the lesion to be a metastatic deposit from adenocarcinoma of the lung. Results and conclusions Given the findings the patient was referred urgently to the lung cancer team who completed a contrast CT scan which identified a large right apical mass with areas of necrosis consistent with neoplastic disease. Borderline mediastinal and supraclavicular lymph nodes and possible suspicious lesions were identified in the left adrenal gland. Given these findings the tumour was staged T4 N2 M0 (N3M1b if supraclavicular node and adrenal lesion involved). The radiologist reporting was unaware of the suspected metastatic lesion in the mandible. Take-home message • The diagnosis of metastatic lesion may be difficult owing to their rarity and clinical presentation. • There is the potential for misdiagnosis as a benign lesion or odontogenic pathology. • Therefore a biopsy is essential especially in patients with a known previous history of malignancy. • Health professionals should be aware of the possible presence of jaw metastasis in patients with atypical presenting symptoms.

Specific MAPK-Associated MicroRNAs in Serum Differentiate Pancreatic Cancer from Autoimmune Pancreatitis.

Pancreatic ductal adenocarcinoma (PDAC) is difficult to distinguish from autoimmune pancreatitis (AIP) because of their clinical and radiological similarities, and therefore simple and minimally invasive surrogate markers for differential diagnosis would be useful. In our previous studies, we identified four microRNAs (miRNAs)–miR-7, miR-34a, miR-181d, and miR-193b –as MAPK-associated microRNAs whose expression was altered significantly with upregulation of the MAPK signaling pathway. Recently it has been reported that these miRNAs could be used as biomarkers in serum samples for accurate diagnosis of pancreatic lesions. The aim of the present study was to evaluate whether these MAPK-associated miRNAs in serum could be used as biomarkers for differentiating PDAC from AIP. We enrolled 69 patients with PDAC, 26 with intraductal papillary mucinous neoplasm (IPMN) and 15 with AIP. The expression of MAPK-associated miRNAs in serum was measured by quantitative real-time PCR. The 2-ΔCT method was used to quantify the expression of miRNAs, and the data were normalized using spiked-in synthetic cel-miR-39. Patients with PDAC or IPMN showed significantly higher amounts of serum MAPK-associated miRNAs than those with AIP (p<0.009 for miR-7, p<0.002 for miR-34a, p<0.001 for miR-181d, p<0.002 for miR-193b). ROC curve analysis demonstrated that these miRNAs had an area under the ROC curve (AUC) of 0.723–0.882 for differentiation between PDAC or IPMN from AIP. Furthermore, serum miR-181d was significantly associated with the presence of metastasis in patients with PDA (p = 0.014). Serum MAPK-associated miRNAs could be novel noninvasive biomarkers for differentiation between PDAC or IPMN and AIP.

Papillary thyroid carcinoma with biomineralization: clinical and morphological features

Papillary thyroid cancer (PTCa) is the most common form of malignant tumors of this organ, covering approximately 70% in the structure of morbidity. Pathological biomineralization is often the first diagnostic sign of ultrasound of the thyroid, so the study of its morphological features is the purpose of our paper. A total of 30 PTCa samples with the signs of biomineralization and 30 PTCa samples without biomineralization were studied. The study used histological, histochemical techniques and scanning electron microscopy with X-ray diffraction. All PTCa patients who had the signs of pathological biomineralization were combined in the first group (30 people) – 27 women and 3 men (9:1). The average age of patients of the first group was 56.93±2.18 years old. The patients were diagnosed with different histological PTCa types: 22 cases of classic variant of PTCa, 3 cases of diffuse sclerotic variant, 2 cases of follicular, 2 cases of tall cell variant, and 1 case of solid variant of PTCa. Patients who had no signs of PTCa mineralization, made up the second group. 30 people – 24 women and 6 men (4:1) – were selected in to the second group. It was found out that in the first group the largest size of tumor site averaged 1.84±0.13 cm, and in the second group the rate was 1.44±0.09 cm (p<0.07). Comparing the number of patients with metastases in both groups (7 – I group, 8 – Group II) and describing the size of tumor nodules, subject to presence of metastases in patients (2.09±0.2 cm and 1.31±0.17 cm), there was significant difference found between indicators of clinical cases of studied groups (p<0.02). The main mineral that is involved in the development of dystrophic calcification in case of PTCa is hydroxyapatite. The presence of hydroxyapatite is characteristic for all the types of PTCa biomineralization.

The number of tumorspheres cultured from peripheral blood is a predictor for presence of metastasis in patients with breast cancer.

BackgroundTumor metastases are the major cause of cancer morbidity and mortality. A subpopulation of tumor cells with stem-like properties is assumed to be responsible for tumor invasion, metastasis, heterogeneity and therapeutic resistance. This population is termed cancer stem cells (CSCs). We have developed a simple method for identification and characterization of circulating cancer stem cells among circulating epithelial tumor cells (CETCs).MethodsCETCs were cultured under conditions favoring growth of tumorspheres from 72 patients with breast cancer, including a subpopulation of 23 patients with metastatic disease. CETCs were determined using the maintrac® method. Gene expression profiles of single CETCs and tumorspheres of the same patients were analyzed using qRT-PCR.ResultsSphere formation was observed in 79 % of patients. We found that the number of tumorspheres depended on stage of disease. Furthermore, the most important factor for growing of tumorspheres is obtaining chemotherapy. Patients with chemotherapy treatment had lower numbers of tumorspheres compared to patients without chemotherapy. Patients with HER2 positive primary tumor had higher number of tumorspheres. Analysis of surface marker expression profile of tumorspheres showed that cells in the spheres had typical phenotype of cancer stem cells. There was no sphere formation in a control group with 50 healthy donors.ConclusionsThis study demonstrates that a small fraction of CETCs has proliferative activity. Identifying the CETC subset with cancer stem cell properties may provide more clinically useful prognostic information. Chemotherapy is the most important component in cancer therapy because it frequently reduces the number of tumorspheres.

Identification of methylation markers for the prediction of nodal metastasis in oral and oropharyngeal squamous cell carcinoma

Hypermethylation is an important mechanism for the dynamic regulation of gene expression, necessary for metastasizing tumour cells. Our aim is to identify methylation tumour markers that have a predictive value for the presence of regional lymph node metastases in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). Significantly differentially expressed genes were retrieved from four reported microarray expression profiles comparing pN0 and pN+ head-neck tumours, and one expression array identifying functionally hypermethylated genes. Additional metastasis-associated genes were included from the literature. Thus genes were selected that influence the development of nodal metastases and might be regulated by methylation. Methylation-specific PCR (MSP) primers were designed and tested on 8 head-neck squamous cell carcinoma cell lines and technically validated on 10 formalin-fixed paraffin-embedded (FFPE) OOSCC cases. Predictive value was assessed in a clinical series of 70 FFPE OOSCC with pathologically determined nodal status. Five out of 28 methylation markers (OCLN, CDKN2A, MGMT, MLH1 and DAPK1) were frequently differentially methylated in OOSCC. Of these, MGMT methylation was associated with pN0 status (P = 0.02) and with lower immunoexpression (P = 0.02). DAPK1 methylation was associated with pN+ status (P = 0.008) but did not associate with protein expression. In conclusion, out of 28 candidate genes, two (7%) showed a predictive value for the pN status. Both genes, DAPK1 and MGMT, have predictive value for nodal metastasis in a clinical group of OOSCC. Therefore DNA methylation markers are capable of contributing to diagnosis and treatment selection in OOSCC. To efficiently identify additional new methylation markers, genome-wide methods are needed.

Abstract 1495: Identification of markers for the presence of lymph nodes metastasis in patients with oral squamous cell carcinomas

Abstract INTRODUCTION: Oral cancer is the most common subset of head and neck squamous cell carcinomas (OSCC). These tumors often have an aggressive clinical outcome hallmarked by a propensity for local invasion and regional nodal metastasis. The presence of metastatic disease in cervical lymph nodes is an important prognostic factor and it influences in the choice of the therapeutic strategy to be adopted. Thus, the identification of molecular markers able to select patients who are at high risk for lymph node metastasis and/or locoregional recurrence could be of great value. Recent studies have shown that microRNAs can be regulators of the tumor metastasis process by the activation of various signaling pathways involved in this process being useful in diagnosis, determination of disease prognosis and prediction of therapeutic response. PURPOSE: to identify microRNAs expressed in OSCC associated with the presence of lymph node metastasis. METHODS: Tumor samples were obtained from patients diagnosed with OSCC at the Head and Neck Surgery Department, Cancer Hospital of Barretos. For microRNA microarrays experiments, total RNA from 32 tumor samples (12 without lymph node metastasis and 12 with metastasis) was extracted labelled and hybridizated Analysis of microarray data was performed using GeneSpring GX 12.0 and R program. RESULTS: This analysis allowed the identification of six microRNAs differentially expressed in the comparison between metastatic and non-metastatic OCCS cases. These microRNAs will be validate and selected by qRT-PCR in an independent cohort of OSCC patients and correlate the molecular data with the clinical features of the patients. Financial Support: FAPESP Note: This abstract was not presented at the meeting. Citation Format: Fernando Tadeu Zamunér, Danielle Calheiros Campelo Maia, André Lopes Carvalho, André Luiz Vettore. Identification of markers for the presence of lymph nodes metastasis in patients with oral squamous cell carcinomas. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1495. doi:10.1158/1538-7445.AM2014-1495

Assessing the Presence of Circulating Tumor Cells in Breast Cancer Patients Using Multiplex Reverse Transcription Polymerase Chain Reaction and Specific Primers for Mammaglobin, Pthrp and Ck19

ABSTRACT Aim: The aim of this study was to develop a multiplex reverse transcription polymerase chain reaction (RT-PCR) assay for the detection of circulating tumor cells in peripheral blood of patients with breast cancer. Methods: Peripheral blood samples were collected from 54 breast cancer patients and 20 healthy blood donors. Subsequently, the samples processed for RNA extraction and then were analyzed for the expression of PTHrP, CK19 and Mammaglobin using specific primers and multiplex PCR. Results: The detection rates in breast cancer patients for PTHrP, CK19 and Mammaglobin were 68.5%, 63% and 22.2% and for healthy donors 10%, 0% and 10%., respectively. The statistical analysis revealed that PTHrP, CK19 and their combination could be used for diagnosing breast cancer. The combination of positive detection rates of PTHrP with CK19 correlated with the presence of distant metastasis in patients with breast cancer, especially with bone metastasis. Moreover, positive detection rates of CK19 correlated with high proliferation rate of breast cancer Conclusions: Multiplex-PCR based detection of circulating tumor cells can provide useful information for the disease stage and presence of metastasis in breast cancer patients. Disclosure: All authors have declared no conflicts of interest.

Predicting the presence of extracranial metastases in patients with brain metastases upon first diagnosis of cancer

This study aimed to determine factors allowing the prediction of extracranial metastases in patients presenting with brain metastases at the first diagnosis of cancer. Data from 659patients with brain metastases upon first diagnosis of cancer were retrospectively analyzed. The parameters age, gender, Karnofsky performance score (KPS), primary tumor type and number of brain metastases were compared between 359patients with extracranial metastases and 300patients without extracranial metastases. Additional analyses were performed for patients with the most unfavorable and those with the most favorable characteristics. The comparison of patients with versus without extracranial metastases revealed significant differences between the groups in terms of KPS (p < 0.001) and number of brain metastases (p < 0.001). Of the study patients, 113had both most unfavorable characteristics, i.e. KPS≤ 50 and ≥ 4brain metastases. The sensitivity for identifying patients with extracranial metastases was 82 %; specificity was 51 %. A total of 50patients had KPS≥ 90 and only one brain metastasis. The sensitivity for identifying patients without extracranial metastases was 86 %; specificity was 58 %. The combination of KPS and the number of brain metastases can help to predict the presence or absence of extracranial metastases.

Hybrid SPECT/CT imaging of sentinel nodes in esophageal cancer: first results

Sentinel node (SN) biopsy in esophageal cancer has the potential of becoming an important tool for ruling out the presence of lymph node metastases in patients opted for less extensive surgery without neoadjuvant treatment. To investigate preoperative SN imaging in esophageal cancer using hybrid single photon emission computed tomography (SPECT)/CT. Eight patients with esophageal cancer scheduled for thoracoabdominal esophagectomy after neoadjuvant treatment, underwent endoscopic submucosal injection of (99m)Tc-nanocoll the day before surgery, followed by imaging with SPECT/CT for preoperative detection. Intraoperative detection of SNs was performed with a gamma probe. SNs were identified by SPECT/CT in 7/8 cases (88%) and by gamma probe in all cases. The median number of identified lymph node stations with SN in the operating field was 1 (range 0-2) for SPECT/CT and 1 (range 1-3) for gamma probe. The median distance between the perceived location of the respective SN according to SPECT/CT and the location identified with the gamma probe was <5 mm (range <5-15 mm). In one patient who had a complete histologic response to neoadjuvant treatment in the primary tumor, there was one single metastasis that was not contained in one of the SNs. Preoperative identification of sentinel nodes with hybrid SPECT/CT after endoscopic injection of radiocolloid is a technique with obvious potential for SN mapping in esophageal cancer.

Abstract P1-01-06: Evaluation of the stage IB designation of the 7th edition of the AJCC staging system: Biologic factors are more important

Abstract Purpose: The stage IB designation was added to the AJCC 7th edition staging system to denote micrometastasis in patients with T1 tumors. We have previously examined this group and found that receptor status and nuclear grade were better survival discriminates than the presence of micrometastases. The current study was undertaken to validate this finding in a larger cohort from the American College of Surgeons Oncology Group (ACOSOG) Z0010 study. Methods: Clinicopathologic and outcomes data from patients enrolled on ACOSOG Z0010 were recorded. All patients underwent breast conserving surgery, sentinel lymph node biopsy and whole breast radiation for clinical T1-2, N0 breast cancer. Sentinel lymph nodes were evaluated by H&amp;E locally and if negative, by immunohistochemistry (IHC) at a central laboratory. Patients were staged according to the 7th edition AJCC system and recurrence-free (RFS), disease-specific (DSS) and overall survival (OS) were determined using the Kaplan-Meier method and compared using the log-rank test. Results: There were 5210 eligible and evaluable patients enrolled on ACOSOG Z0010. AJCC stage distribution was known in 4590 and included: 2849 (62.0%) stage IA, 376 (8.2%) stage IB, 878 (19.1%) stage IIA, 322 (7.0%) stage IIB, and 170 (3.7%) stage III. Median follow-up for the cohort was 9.0 years (range 0–12.6). Five and 10-year RFS, DSS and OS rates for patients with stage IA versus IB disease are shown in table 1. There were no significant differences between groups. When all stage I patients (stage IA and IB) were evaluated by ER status (positive vs negative) or grade (grade 1 vs 2 vs 3), these biologic factors were able to significantly discriminate patients with respect to RFS, DSS and OS (table 2). Conclusion: Differentiating patients with micrometastases (stage IB) from node negative patients (stage IA) does not stratify patients well with respect to survival. Biologic factors including ER status and grade are better discriminants of survival than the presence of small volume nodal metastases in patients with early stage breast cancer. Breast cancer staging should include biologic factors from the primary tumor. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-06.

Evaluation of the stage IB designation of the 7th edition of the AJCC Staging System.

1130 Background: Recent data from large cooperative group trials have questioned the relevance of small volume metastases identified in the sentinel lymph nodes (SLN) of early stage breast cancer patients. The 7th ed. of the AJCC staging system differentiates node negative patients (stage IA) from those with micrometastases (stage IB) or macrometastases (stage II or III). This study was undertaken to determine the utility of the stage IB designation. Methods: Review of a prospectively maintained database identified 3474 patients who underwent SLN biopsy between 1993 and 2007. Clinicopathologic and outcomes data were recorded and patients staged according to the 7th ed. AJCC system. Recurrence-free (RFS), disease-specific (DSS) and overall survival (OS) were determined using the Kaplan-Meier method and compared using the log-rank test. Results: AJCC stage distribution included: 2246 (65%) stage IA, 207 (6%) stage IB, 685 (20%) stage IIA, 209 (6%) stage IIB, and 127 (3%) stage III. For patients with stage IB disease, SLN micrometastasis was identified by H&amp;E in 173 (84%) and immunohistochemistry (IHC) in 34 (16%); suggesting that 16% would have been staged IA if enhanced evaluation had not been performed. Median follow-up was 6.1 yrs (range 0-17.2). The 5-yr RFS,DSS and OS rates for patients with stage IB disease were 98.0%, 99.5%, and 95.9% respectively, which did not differ significantly from patients with stage IA disease who had 5-year RFS,DSS and OS rates of (97.5%, p=.9), (98.8%, p=.7) and (96.2%, p=.8). When all stage I patients (IA and IB) were evaluated by ER status or grade (grade 1 vs 2 vs 3), these biologic factors were able to significantly discriminate patients with respect to RFS, DSS and OS. Conclusions: Differentiating patients with micrometastases from node negative patients does not stratify patients with respect to survival. Biologic factors (ER status and grade) are better discriminants of survival than the presence of small volume nodal metastases in patients with early stage disease. These data do not support routine use of IHC or alterations in adjuvant therapy decisions based on identification of SLN micrometastases.