In this multi-institutional prospective study, we evaluated whether we could identify risk factors predictive for non-sentinel lymph node (non-SN) metastases in breast cancer patients with a positive ...sentinel lymph node (SN).
In this multi-institutional study, 541 eligible breast cancer patients were included prospectively.
The occurrence of non-SN metastases was related to the size of the SN metastasis (P = .02), primary tumor size (P = .001), and lymphovascular invasion (P = .07). The adjusted odds ratio was 3.1 for SN micro-metastasis compared with SN isolated tumor cells, 4.0 for SN macro-metastasis versus SN isolated tumor cells, 3.1 for tumor size (>3.0 cm compared with </=3.0 cm), and 2.0 for lymphovascular invasion (yes versus no). There were no positive non-SNs when the primary tumor size was </=1.0 cm (n = 24) 95% confidence interval (95% CI) 0%-14.0%. The proportion of positive non-SNs ranged in a prognostic logistic regression model from 9.7% (95% CI 4.0%-23.0%) for patients with SN isolated tumor cells, tumor size of 1.1-3.0 cm, and without vessel invasion, to 72.6% (95% CI 47.0%-89.0%) for patients with SN macro-metastasis, tumor size >3.0 cm, and with vessel invasion.
We identified three predictive factors for non-SN metastases in breast cancer patients with a positive SN: size of the SN metastasis; primary tumor size; and vessel invasion. We were not able to identify a specific group of patients with a positive SN in whom the risk for non-SN metastases was less than 5%.
OBJECTIVE:The objective of this study was to evaluate the performance of a new commercially available open breast coil and compatible intervention device (Machnet) for magnetic resonance image ...(MRI)-guided breast interventions.
MATERIALS AND METHODS:Breast lesions detected on MRI were evaluated using MRI-guided core biopsy (n = 20) and/or preoperative wire localization (n = 23) on histologic outcome and accuracy of localization. Time needed to perform a procedure and occurring problems were recorded.
RESULTS:Mean lesion size was <10 mm. Two of 20 lesions could not be biopsied because they were out of range for the device. Biopsies were conclusive in half of the cases; most lesions missed were <10 mm. The average accuracy for needle placement in the localization procedures was less than 2 mm (range, 0–5 mm). The average procedure time was 40 minutes for a biopsy procedure and 33 minutes for an MRI-guided localization.
CONCLUSIONS:Preoperative MRI-guided localizations can be performed quickly and accurately. However, in MRI-guided core biopsies, especially in small lesions, the device does not guarantee conclusive histologic evaluation of the lesion targeted.
Esophageal cancer (EC) has a globally increasing incidence with poor curative treatment options and survival rates. Crucial risk factors are exposure to toxins or carcinogens. Microsomal epoxide ...hydrolase (mEH) is a biotransformation enzyme essential for the detoxification of xenobiotics. Polymorphisms in exon 3 and exon 4 of the microsomal epoxide hydrolase gene (EPHX1) modify catalytic activity of this enzyme and subsequently may play a role in EC etiology. This case-control study investigated whether these polymorphisms in the EPHX1 gene influence esophageal cancer susceptibility in a Dutch Caucasian population. A case-control study including 349 Caucasian EC patients and 581 Caucasian healthy controls was conducted and the polymorphisms Tyr113His (exon 3) and His139Arg (exon 4) in the EPHX1 gene were determined, using polymerase chain reaction. The distribution of exon 3 and exon 4 genotypes were compared between cases and controls. Analyses included a stratification according to tumor histology; esophageal adenocarcinoma (EAC) or squamous cell carcinoma (ESCC). Furthermore, on the basis of allelic in vitro enzyme activity assays, exon 3 and 4 genotypes were combined and categorized according to their predicted high, medium or low enzyme activity. Homozygosity and heterozygosity for both exon 3 and 4 polymorphisms were correlated with a decreased esophageal squamous cell carcinoma risk. Heterozygosity and homozygosity for both polymorphisms correlated with an increased and a decreased esophageal adenocarcinoma risk, respectively. Predicted intermediate and high activity genotypes were risk and protective factors for esophageal squamous cell carcinoma and esophageal adenocarcinoma, respectively. However, none of these associations were statistically significant. In conclusion, the polymorphisms in exon 3 and exon 4 of the EPHX1 gene do not seem to be modifiers of esophageal squamous cell carcinoma or esophageal adenocarcinoma risk in Dutch Caucasians.
In recent years, it has become evident that T cells can recognize peptides of melanocytic lineage antigens such as gp100, MART-1, and tyrosinase at the tumor cell surface and can subsequently destroy ...these cells. It is thus feasible to develop immunotherapeutic approaches based on the melanocytic marker profiles of melanoma cells. One of the predictors of the success rate of such a treatment is the extent of positive (target) tumor cells within the lesions of the patient. First, we investigated the presence of these three proteins in 18 human melanoma cell lines using RT-PCR and immunohistochemistry. In 11 cell lines, mRNA and protein of all three markers could be detected; in one cell line, only two markers were present, and six melanoma cell lines showed no evidence for these markers. Secondly, we stained frozen sections of 105 human melanocytic lesions, 13 common nevocellular nevi, 13 atypical nevi, 13 early primary melanomas (Breslow < 1.5 mm), 25 advanced primary melanomas (aPM; Breslow > or =1.5 mm), and 41 melanoma metastases (MM) with antibodies against glycoprotein 100, melanoma antigen recognized by T cells, and tyrosinase. In addition, we used the 3,4-dihydroxy-L-phenylalanine reaction to detect tyrosinase enzyme activity as a confirmation of the tyrosinase immunohistochemical results in a subset of the lesions. In the benign lesions, glycoprotein 100 was more prominently expressed in epidermal melanocytes, whereas melanoma antigen recognized by T cells was encountered in all or nearly all dermal melanocytes in all nevocellular nevi and atypical nevus lesions. Tyrosinase was found in a lower percentage of melanocytes, both in the epidermis and in the dermis within these lesions. With regard to heterogeneity of staining within the malignant lesions, we found that 54% (early primary melanomas), 48% (aPMs), and 56% (MM) of the lesions stained within the same staining category for all three proteins studied. Approximately 17% of the aPM and MM lesions did not show positive tumor cells for any of the three proteins. We conclude that a subgroup of patients with high expression should be selected for immunotherapeutic treatment approaches based on the presence of these proteins.
Factors determining individual susceptibility to esophageal cancer or premalignant Barrett's epithelium are still largely unclear. An imbalance between phase I drug metabolism e.g., cytochrome P450 ...(CYP) and phase II detoxification e.g., glutathione S-transferase (GST) may contribute to the development of these diseases. Polymorphic variants in the CYP1A1 gene were described leading to increased levels of bioactive compounds, whereas polymorphisms in GST genes often resulted in impaired detoxification. We studied the frequencies of polymorphic variants in CYP1A1, GSTP1, GSTT1, and GSTM1 genes in 98 patients with Barrett's epithelium and 34 patients with esophageal cancer. The results were compared with those obtained from 247 healthy blood donors. DNA was extracted, and PCR-RFLP methods were used to detect genetic polymorphisms. Chi2 analysis, Spearman rank correlation, and Wilcoxon rank sum tests were used for statistical evaluation. Polymorphisms in CYP1A1, GSTM1, and GSTT1 occurred at an equal frequency in patients and controls. Occurrence of the polymorphic GSTP1b variant in the GSTP1 gene resulted in a significantly lower GST enzyme activity (P < 0.05), and GSTP1b was found significantly more often in patients with Barrett's epithelium (70%; P < 0.001) and patients with esophageal adenocarcinoma (76%; P = 0.005), as compared to healthy blood donors (41%). In conclusion, presence of the GSTP1b allele leads to lower GST enzyme activity levels and, consequently, impaired detoxification. This most important esophageal GST isoform may, therefore, contribute to the development of Barrett's epithelium and adenocarcinoma.
It is hypothesized that excessive generation of reactive oxygen species (ROS) by phagocytes or leakage from mitochondria may harm key genes or proteins responsible for intestinal cell homeostasis. ...This may initiate the multistage process of colon cancer development. The present study investigates whether ROS production by whole blood may contribute to the etiology of colorectal cancer (CRC). Whole–blood oxygen radical production was measured by luminol–enhanced chemiluminescence and performed in fourfold with and without the stimuli phorbol 12–myristate 13–acetate (PMA) and serum–treated zymosan (STZ). We evaluated patients (i) with a history of sporadic CRC at least 3 months after surgery, (ii) who were hereditary nonpolyposis colorectal cancer (HNPCC) gene carriers, and (iii) with familial adenomatous polyposis (FAP). For each patient group (
n = 20) an age- and gender-matched healthy control group was measured. Unstimulated and PMA-stimulated values for maximal oxygen radical production were significantly higher in patients with sporadic CRC in comparison to controls (
p = 0.01,
p = 0.04, respectively). Furthermore, trends toward higher unstimulated and PMA-stimulated area under the curve chemiluminescence were seen in CRC patients compared with controls (
p = 0.08,
p = 0.09, respectively). In patients with HNPCC or FAP, unstimulated or PMA- or STZ-stimulated chemiluminescence did not differ compared to their control groups. In conclusion, whole–blood oxygen radical production was higher in patients with a history of sporadic CRC, in comparison with age- and gender-matched controls, which indicates that ROS may play a role in the etiology of sporadic CRC.
