Increased Screening Rates for Thyroid Cancer Among Residents Living Near Nuclear Power Plants.

Frequent screening for thyroid cancer has been suggested as a probable explanation for the observed high risk of thyroid cancer in nuclear power plant (NPP) areas. We aimed to compare thyroid cancer screening rates of residents living near NPPs to those of the general population. This study utilized data from two national survey-based studies in 2016 and in 2014, respectively, for residents (n = 1,200) living in administrative districts within 5 km of NPP sites as the interest group, and the general population (n = 228,712) including distant-living residents (n = 19,100) in administrative districts within 30 km of NPP sites as reference groups. We observed an increase in screening rates in residents near NPPs, which may lead to a higher possibility of thyroid cancer detection. Therefore, further epidemiological studies investigating radiation-induced thyroid cancer risk among residents near NPPs should be carefully designed and interpreted considering possible detection bias.

Estimation of the historical radiation dose of Korean radiation workers, 1961-1983.

Accurate dosimetry plays a key role in evaluating the radiation-induced health risks of radiation workers. The National Dose Registry in Korea contains the dose records of radiation workers in nuclear-related occupations since 1984. Thus, radiation doses for workers before 1984 are often sparse or missing. This study aimed to estimate the historical radiation dose before 1984 for radiation workers in Korea based on dose reconstruction models. The dose reconstruction models were derived from the nationwide self-administered questionnaire survey and the personal badge doses for workers in the cohort of the Korean Radiation Worker Study. The mean estimated annual doses between 1984 and 2016 from the dose reconstruction model were 4.67-0.6 mSv, which closely matched the reported doses of 4.51-0.43 mSv. The mean estimated annual doses between 1961 and 1983 based on the exposure scenarios developed by factors associated with radiation doses ranged from 11.08 to 4.82 mSv. The mean estimated annual doses of individuals in the cohort from 1961 to 1983 ranged from 11.15 to 4.88 mSv. Although caution needs to be exercised in the interpretation of these estimations due to uncertainty owed to the nature of extrapolation beyond the range of observed data, this study offers a sense of the radiation doses for workers during Korea's early period of radiation-related activities, which can be a useful piece of information for radiation-induced health risk assessments.

Assessment of working environment and personal dosimeter-wearing compliance of industrial radiographers based on chromosome aberration frequencies.

Industrial radiographers are exposed to relatively higher doses of radiation than other radiation-exposed workers in South Korea. The objective of our study was to investigate the impact of specific occupational conditions on chromosome aberration frequency and evaluate dosimeter-wearing compliance of industrial radiographers in Korea. We studied individual and occupational characteristics of 120 industrial radiographers working in South Korea and evaluated the frequency of dicentrics and translocations in chromosomes to estimate radiation exposure. The association between working conditions and chromosome aberration frequencies was assessed by Poisson regression analysis after adjusting for confounding factors. Legal personal dosimeter-wearing compliance among workers was investigated by correlation analysis between recorded dose and chromosome aberration frequency. Daily average number of radiographic films used in the last six months was associated with dicentrics frequency. Workers performing site radiography showed significantly higher translocation frequency than those working predominantly in shielded enclosures. The correlation between chromosome aberration frequency and recorded dose was higher in workers in the radiography occupation since 2012 (new workers) than other veteran workers. Our study found that site radiography could affect actual radiation exposure to workers. Controlling these working conditions and making an effort to improve personal dosimeter-wearing compliance among veteran workers as well as new workers may be necessary to reduce radiation exposure as much as possible in their workplace.

Projected lifetime cancer risks from occupational radiation exposure among diagnostic medical radiation workers in South Korea.

BACKGROUND: Timely assessment of cancer risk from current radiation exposure among medical radiation workers can contribute to the development of strategies to prevent excessive occupational radiation exposure. The purpose of the present study is to estimate the lifetime risk of cancers induced by occupational radiation exposure among medical radiation workers. METHODS: Using estimated organ doses and the RadRAT risk assessment tool, the lifetime cancer risk was estimated among medical radiation workers who were enrolled in the Korean National Dose Registry from 1996 to 2011. Median doses were used for estimating the risk because of the skewed distribution of radiation doses. Realistic representative exposure scenarios in the study population based on sex, job start year, and occupational group were created for calculating the lifetime attributable risk (LAR) and lifetime fractional risk (LFR). RESULTS: The mean estimated lifetime cancer risk from occupational radiation exposure varied significantly by sex and occupational group. The highest LAR was observed in male and female radiologic technologists who started work in 1991 (264.4/100,000 and 391.2/100,000, respectively). Female workers had a higher risk of radiation-related excess cancer, although they were exposed to lower radiation doses than male workers. The higher LAR among women was attributable primarily to excess breast and thyroid cancer risks. LARs among men were higher than women in most other cancer sites. With respect to organ sites, LAR of colon cancer (44.3/100,000) was the highest in male radiologic technologists, whereas LAR of thyroid cancer (222.0/100,000) was the highest in female radiologic technologists among workers who started radiologic practice in 1991. Thyroid and bladder cancers had the highest LFR among radiologic technologists. CONCLUSIONS: Our findings provide an assessment of the potential cancer risk from occupational radiation exposure among medical radiation workers, based on current knowledge about radiation risk. Although the radiation-related risk was small in most cases, it varied widely by sex and occupational group, and the risk would be underestimated due to the use of median, rather than mean, doses. Therefore, careful monitoring is necessary to optimize radiation doses and protect medical radiation workers from potential health risks, particularly female radiologic technologists.

Epithelial cell shape change of Drosophila as a biomonitoring model for the dose assessment of environmental radiation.

Inevitable exposure to ionizing radiation from natural and human-made sources has been increasing over time. After nuclear disasters, such as the Fukushima accident, the public concerns on health risk of radiation exposure because of radioactive contamination of the environment have increased. However, it is very difficult to assess the biological effects of exposure caused by environmental radiation. A reliable and rapid bioassay to monitor the physiological effects of radiation exposure is therefore needed. Here, we quantitatively analyzed the changes in cell shape in Drosophila epidermis after irradiation as a model for biomonitoring of radiation. Interestingly, the number of irregularly shaped epithelial cells was increased by irradiation in a dose-dependent manner. A dose-response curve constructed with the obtained data suggests that the measurement of the number of irregular shaped cell in the epidermis is useful for the assessment of radiation dose. In addition, a comparison of the variation in the different samples and the data scored by different observers showed that our evaluation for cellular morphology was highly reliable and accurate and would, therefore, have immense practical application. Overall, our study suggests that detection of morphological changes in the epithelial cells is one of the efficient ways to quantify the levels of exposure to radioactive radiation from the environment.

Usefulness of cancer-free survival in estimating the lifetime attributable risk of cancer incidence from radiation exposure.

Risk projection models estimating the lifetime cancer risk from radiation exposure are generally based on exposure dose, age at exposure, attained age, gender and study-population-specific factors such as baseline cancer risks and survival rates. Because such models have mostly been based on the Life Span Study cohort of Japanese atomic bomb survivors, the baseline risks and survival rates in the target population should be considered when applying the cancer risk. The survival function used in the risk projection models that are commonly used in the radiological protection field to estimate the cancer risk from medical or occupational exposure is based on all-cause mortality. Thus, it may not be accurate for estimating the lifetime risk of high-incidence but not life-threatening cancer with a long-term survival rate. Herein, we present the lifetime attributable risk (LAR) estimates of all solid cancers except thyroid cancer, thyroid cancer, and leukemia except chronic lymphocytic leukemia in South Korea for lifetime exposure to 1 mGy per year using the cancer-free survival function, as recently applied in the Fukushima health risk assessment by the World Health Organization. Compared with the estimates of LARs using an overall survival function solely based on all-cause mortality, the LARs of all solid cancers except thyroid cancer, and thyroid cancer evaluated using the cancer-free survival function, decreased by approximately 13% and 1% for men and 9% and 5% for women, respectively. The LAR of leukemia except chronic lymphocytic leukemia barely changed for either gender owing to the small absolute difference between its incidence and mortality. Given that many cancers have a high curative rate and low mortality rate, using a survival function solely based on all-cause mortality may cause an overestimation of the lifetime risk of cancer incidence. The lifetime fractional risk was robust against the choice of survival function.

Is the Linear No-Threshold Dose-Response Paradigm Still Necessary for the Assessment of Health Effects of Low Dose Radiation?

Inevitable human exposure to ionizing radiation from man-made sources has been increased with the proceeding of human civilization and consequently public concerns focus on the possible risk to human health. Moreover, Fukushima nuclear power plant accidents after the 2011 East-Japan earthquake and tsunami has brought the great fear and anxiety for the exposure of radiation at low levels, even much lower levels similar to natural background. Health effects of low dose radiation less than 100 mSv have been debated whether they are beneficial or detrimental because sample sizes were not large enough to allow epidemiological detection of excess effects and there was lack of consistency among the available experimental data. We have reviewed an extensive literature on the low dose radiation effects in both radiation biology and epidemiology, and highlighted some of the controversies therein. This article could provide a reasonable view of utilizing radiation for human life and responding to the public questions about radiation risk. In addition, it suggests the necessity of integrated studies of radiobiology and epidemiology at the national level in order to collect more systematic and profound information about health effects of low dose radiation.

Estimates of Radiation Doses and Cancer Risk from Food Intake in Korea.

The aim of this study was to estimate internal radiation doses and lifetime cancer risk from food ingestion. Radiation doses from food intake were calculated using the Korea National Health and Nutrition Examination Survey and the measured radioactivity of (134)Cs, (137)Cs, and (131)I from the Ministry of Food and Drug Safety in Korea. Total number of measured data was 8,496 (3,643 for agricultural products, 644 for livestock products, 43 for milk products, 3,193 for marine products, and 973 for processed food). Cancer risk was calculated by multiplying the estimated committed effective dose and the detriment adjusted nominal risk coefficients recommended by the International Commission on Radiation Protection. The lifetime committed effective doses from the daily diet are ranged 2.957-3.710 mSv. Excess lifetime cancer risks are 14.4-18.1, 0.4-0.5, and 1.8-2.3 per 100,000 for all solid cancers combined, thyroid cancer, and leukemia, respectively.

Intensive postoperative glucose control reduces the surgical site infection rates in gynecologic oncology patients.

OBJECTIVE: SSI rates after gynecologic oncology surgery vary from 5% to 35%, but are up to 45% in patients with diabetes mellitus (DM). Strict postoperative glucose control by insulin infusion has been shown to lower morbidity, but not specifically SSI rates. Our project studied continuous postoperative insulin infusion for 24h for gynecologic oncology patients with DM and hyperglycemia with a target blood glucose of <139 mL/dL and a primary outcome of the protocol's impact on SSI rates. METHODS: We compared SSI rates retrospectively among three groups. Group 1 was composed of patients with DM whose blood glucose was controlled with intermittent subcutaneous insulin injections. Group 2 was composed of patients with DM and postoperative hyperglycemia whose blood glucose was controlled by insulin infusion. Group 3 was composed of patients with neither DM nor hyperglycemia. We controlled for all relevant factors associated with SSI. RESULTS: We studied a total of 372 patients. Patients in Group 2 had an SSI rate of 26/135 (19%), similar to patients in Group 3 whose rate was 19/89 (21%). Both were significantly lower than the SSI rate (43/148, 29%) of patients in Group 1. This reduction of 35% is significant (p = 0.02). Multivariate analysis showed an odd ratio = 0.5 (0.28-0.91) in reducing SSI rates after instituting this protocol. CONCLUSIONS: Initiating intensive glycemic control for 24h after gynecologic oncology surgery in patients with DM and postoperative hyperglycemia lowers the SSI rate by 35% (OR = 0.5) compared to patients receiving intermittent sliding scale insulin and to a rate equivalent to non-diabetics.

Thrombocytosis is Predictive of Postoperative Pulmonary Embolism in Patients With Gynecologic Cancer.

OBJECTIVES: The prompt diagnosis of postoperative pulmonary embolism (PE) in gynecologic oncology patients is imperative, but the clinical presentation is nonspecific in this high-risk group. We sought to determine risk factors and clinical findings that may assist clinicians in diagnosing PE in the inpatient setting. METHODS: Radiology data were queried to identify patients with gynecologic cancer who had a postoperative PE evaluation with computed tomography pulmonary angiography (CT-PA). Patient clinical findings at the time of the PE evaluation were abstracted, and univariate and multivariate regression analyses were performed to identify predictors of PE. RESULTS: For 6 years, there were 2498 major gynecologic oncology surgical procedures performed at our institution. Within 14 days of surgery, 107 CT-PA studies were obtained with a positive study rate of 24.3%. In patients with and without PE, there was no significant difference noted for age, oxygen saturations, body mass index and heart rate. After controlling for stage, history of venous thromboembolism (VTE), heart rate, and oxygen saturation, platelet count (odds ratio, 1.26 per 50 counts increase; 95% confidence interval, 1.07-1.48; P = 0.006) and history of VTE (odds ratio, 17.1; 95% confidence interval, 1.77-Inf, P = 0.014) were identified as independent predictors of PE in the multivariate model. CONCLUSIONS: Although clinicians often use tachycardia and low oxygen saturation as triggers to order PE imaging studies, these signs have a very low specificity. Given the findings of our study, accounting for high platelet count and history of VTE increases the pretest probability of CT-PA study.

Increased Notch1 expression is associated with poor overall survival in patients with ovarian cancer.

OBJECTIVE: Despite improvements in surgery and chemotherapy, ovarian cancer remains a deadly disease in need of improved therapies. We have previously shown that Notch1 intracellular domain (NICD) is highly expressed in ovarian cancer. We have also shown that NICD inhibition can lead to growth arrest in ovarian cancer cells. The objective of the current study was to delineate whether NICD expression correlates with prognosis of women with ovarian cancer. METHODS: After the institutional review board approval, patients with a diagnosis of primary ovarian cancer between the years 2001 and 2007 who underwent surgery at our institution were identified. Paraffin blocks from the primary ovarian tumor were analyzed, and core samples were obtained to build a tissue microarray. Cytoplasmic NICD expression was assessed by quantitative immunofluorescent morphometry using the automated quantitative analysis system. These results were correlated with clinical and pathology data retrieved from the patient records. RESULTS: We identified 328 patients with primary ovarian cancer during this period. Seventeen percent of patients had stage I, 11% had stage II, 59% had stage III, and 13% had stage IV disease. Most patients (70%) had papillary serous histology, and most (86%) underwent optimal debulking to less than 1 cm of residual disease. High NICD expression was found to correlate strongly with low overall survival (P = 0.001). This effect remained in multivariate analysis (P = 0.023). CONCLUSIONS: High expression of NICD in the primary tumor of women with ovarian cancer is an independently poor prognostic factor for overall survival. Further research into the therapeutic inhibition of the Notch1 pathway is warranted.

Diminished Utilization of in Vitro Fertilization Following Ovarian Transposition in Cervical Cancer Patients.

OBJECTIVE: To assess subsequent utilization of fertility treatment in reproductive-age women with cervical cancer (CC) who underwent ovarian transposition (OT) to preserve fertility prior to pelvic radiation. STUDY DESIGN: This is a case series of 216 CC patients seen in a comprehensive cancer center. Sixteen patients underwent OT for fertility preservation prior to pelvic radiation. Patients were assessed for utilization of fertility treatment, follicle-stimulating hormone (FSH) levels as a measure of ovarian reserve, and functional assessment of chronic illness therapy-cervix cancer (FACT-CX) to assess quality of life after OT. RESULTS: Of the patients, 94% of patients [corrected] maintained regular menstrual cycles 3 years after ovarian transposition (OT) [corrected] surgery (15/16). When measured (n = 5), serum FSH was normal at baseline and showed a transient elevation at 3 months following chemoradiation, with a return to normal levels at 6 months (means, 6.33 ± 2.94, 48.44 ± 18.63, and 12.52 ± 8.25 mIU/mL, respectively). Only 1 patient in this series attempted fertility treatment (in vitro fertilization) following OT, and she did not become pregnant. FACT-CX indicated that quality of life did not change significantly over the 6 months' duration following OT and chemoradiation therapy. CONCLUSION: OT preserves menstrual cycle regularity without negatively impacting patients' quality of life. The utility of OT as an effective fertility preservation option is hampered by the low utilization rate of in vitro fertilization and lack of ovarian reserve assessment following OT.

Intratumoral hu14.18-IL-2 (IC) induces local and systemic antitumor effects that involve both activated T and NK cells as well as enhanced IC retention.

hu14.18-IL-2 (IC) is an immunocytokine consisting of human IL-2 linked to hu14.18 mAb, which recognizes the GD2 disialoganglioside. Phase 2 clinical trials of i.v. hu14.18-IL-2 (i.v.-IC) in neuroblastoma and melanoma are underway and have already demonstrated activity in neuroblastoma. We showed previously that intratumoral hu14.18-IL-2 (IT-IC) results in enhanced antitumor activity in mouse models compared with i.v.-IC. The studies presented in this article were designed to determine the mechanisms involved in this enhanced activity and to support the future clinical testing of intratumoral administration of immunocytokines. Improved survival and inhibition of growth of both local and distant tumors were observed in A/J mice bearing s.c. NXS2 neuroblastomas treated with IT-IC compared with those treated with i.v.-IC or control mice. The local and systemic antitumor effects of IT-IC were inhibited by depletion of NK cells or T cells. IT-IC resulted in increased NKG2D receptors on intratumoral NKG2A/C/E⁺ NKp46⁺ NK cells and NKG2A/C/E⁺ CD8⁺ T cells compared with control mice or mice treated with i.v.-IC. NKG2D levels were augmented more in tumor-infiltrating lymphocytes compared with splenocytes, supporting the localized nature of the intratumoral changes induced by IT-IC treatment. Prolonged retention of IC at the tumor site was seen with IT-IC compared with i.v.-IC. Overall, IT-IC resulted in increased numbers of activated T and NK cells within tumors, better IC retention in the tumor, enhanced inhibition of tumor growth, and improved survival compared with i.v.-IC.

Intratumoral treatment of smaller mouse neuroblastoma tumors with a recombinant protein consisting of IL-2 linked to the hu14.18 antibody increases intratumoral CD8+ T and NK cells and improves survival.

Hu14.18-IL2 is an immunocytokine (IC) consisting of human IL-2 linked to hu14.18 mAb, which recognizes GD2 disialoganglioside. Phase II clinical trials of intravenous-hu14.18-IL2 (IV-IC) in neuroblastoma and melanoma are underway, and have already demonstrated activity in neuroblastoma. In our Phase II trial, lower neuroblastoma burden at the time of treatment was associated with a greater likelihood of clinical response to IV-IC. We have previously shown that intratumoral-hu14.18-IL2 (IT-IC) compared to IV-IC results in enhanced local and systemic antitumor activity in tumor-bearing mice. We utilized a mouse model to investigate the impact of tumor burden on hu14.18-IL2 treatment efficacy in IV- versus IT-treated animals. Studies presented here describe the analyses of tumor burden at the initiation of treatment and its effects on treatment efficacy, survival, and tumor-infiltrating leukocytes in A/J mice bearing subcutaneous NXS2 neuroblastoma. We show that smaller tumor burden at treatment initiation is associated with increased infiltration of NK and CD8+ T cells and increased overall survival. NXS2 tumor shrinkage shortly after completion of the 3 days of hu14.18-IL2 treatment is necessary for long-term survival. This model demonstrates that tumor size is a strong predictor of hu14.18-IL2-induced lymphocyte infiltration and treatment outcome.

The role of appendectomy for mucinous ovarian neoplasms.

OBJECTIVE: To determine how frequently the appendix harbors pathology in women having surgery for mucinous neoplasms of the ovary and assess the associated morbidity. STUDY DESIGN: A retrospective chart review of patients operated on at our institution with the diagnosis of a mucinous neoplasm of the ovary or appendix. RESULTS: A total of 327 cases were identified. Of the 309 women with mucinous ovarian neoplasms, 197 (64%) were benign, 68 (22%) low malignancy potential, and 44 (14%) were invasive. Of 155 appendectomies performed, only 1 metastatic low grade mucinous appendiceal tumor was found, but this appendix was grossly abnormal. There was no association between wound complications and appendectomy. CONCLUSION: When a grossly normal appendix is removed during surgery for a mucinous ovarian neoplasm without evidence of pseudomyxoma peritonei, no primary or metastatic mucinous appendiceal tumors are found.

A new diagnostic test for endometrial cancer?: Cytology analysis of sonohysterography distention media.

OBJECTIVE: During saline-infused sonohysterography (SIS), the distension fluid is typically discarded. If cytology analysis could identify those patients with endometrial cancer, many women would be spared from further procedures. METHODS: Thirty consecutive patients with clinical stage I or II endometrial adenocarcinoma were prospectively recruited preoperatively. Saline-infused sonohysterography was performed by instilling 5 mL of saline, withdrawing and sending for analysis. Saline was reinfused until complete SIS images were obtained and sent separately for cytology. RESULTS: Of the 30 women enrolled, SIS was technically successful in 29. Demographics included mean age (60.5 ± 6.99 years), body mass index (35.55 ± 8.18 kg/m), endometrioid histology (76%), and grade (grade 1, 67%). Prestudy diagnostic method included biopsy (70%), dilatation and curettage (17%), and hysteroscopy (10%). Adequate cytology specimens were obtained in 66% of the 5 mL flushes and 72% of the complete SIS collections. Of adequate specimens, the sensitivities to detect endometrial cancer for the 5-mL, complete, and combined fluid samples were 26% (95% confidence interval, 9%-51%), 36% (17%-59%), and 42% (22%-63%). Sensitivity based on the whole study sample (N = 30) was 33% (17%-53%). Statistical significance was not found in the association between a positive test and age, body mass index, grade, diagnostic method, or volume instilled or aspirated. CONCLUSIONS: Most patients with early endometrial cancer can undergo SIS procedures with adequate cytology specimens obtained from distention media. However, the sensitivity is low, and refinements are necessary before utilizing as a diagnostic test. In cases with positive results, the patient may be able to avoid other costly and painful procedures.

Characteristics and Trends of Occupational Radiation Doses among Korean Radiation Workers (1984-2020).

ABSTRACT: This study identified characteristics of occupational radiation doses among Korean radiation workers from 1984-2020 using the National Dose Registry. The overall mean effective dose from 1984-2020 was 1.05 mSv y -1 , with the highest mean effective dose of 2.61 mSv y -1 for non-destructive testing workers. The mean effective dose gradually decreased from 2.97 mSv in 1984 to 0.34 mSv in 2020. The largest decline ratio between 1984 and 2020 was observed in educational institutions at 97.4% (0.84 mSv in 1984 and 0.02 mSv in 2020), followed by industries at 96.5% (2.55 mSv in 1984 and 0.09 mSv in 2020). Compared to 1984, the individual dose-distribution and collective dose-distribution ratios in 2020 decreased by 82.6-99% and 53.7-94.7%, respectively. This downward trend was consistent in all occupations, while decline characteristics were different depending on occupation types, work experience, and changes in radiation safety regulations. Considering that some changes in radiation doses in the registry could be solely based on changing the recording mode regardless of the actual changes in radiation doses, a careful understanding of radiation doses in the registry is particularly relevant for future epidemiological studies.

Organ dose reconstruction for the radiation epidemiological study of Korean radiation workers: the first dose evaluation for the Korean Radiation Worker Study (KRWS).

The Korea Institute of Radiological and Medical Sciences has started a radiation epidemiological study, titled "Korean Radiation Worker Study," to evaluate the health effects of occupational exposure to radiation. As a part of this study, we investigated the methodologies and results of reconstructing organ-specific absorbed doses based on personal dose equivalent, Hp(10), reported from 1984 to 2019 for 20,605 Korean radiation workers. For the organ dose reconstruction, representative exposure scenarios (i.e., radiation energy and exposure geometry) were first determined according to occupational groups, and dose coefficients for converting Hp(10) to organ absorbed doses were then appropriately taken based on the exposure scenarios. Individual annual doses and individual cumulative doses were reconstructed for 27 organs, and the highest values were observed in the thyroid doses (on average 0.77 mGy/y and 10.47 mGy, respectively). Mean values of individual cumulative absorbed doses for the red bone marrow, colon, and lungs were 7.83, 8.78, and 8.43 mSv, respectively. Most of the organ doses were maximum for industrial radiographers, followed by nuclear power plant workers, medical workers, and other facility workers. The organ dose database established in this study will be utilized for organ-specific risk estimation in the Korean Radiation Worker Study.

Syndecan-1 in breast cancer stroma fibroblasts regulates extracellular matrix fiber organization and carcinoma cell motility.

Stromal fibroblasts of breast carcinomas frequently express the cell surface proteoglycan syndecan-1 (Sdc1). In human breast carcinoma samples, stromal Sdc1 expression correlates with an organized, parallel, extracellular matrix (ECM) fiber architecture. To examine a possible link between stromal Sdc1 and the fiber architecture, we generated bioactive cell-free three-dimensional ECMs from cultures of Sdc1-positive and Sdc1-negative murine and human mammary fibroblasts (termed ECM-Sdc1 and ECM-mock, respectively). Indeed, ECM-Sdc1 showed a parallel fiber architecture that contrasted markedly with the random fiber arrangement of ECM-mock. When breast carcinoma cells were seeded into the fibroblast-free ECMs, ECM-Sdc1, but not ECM-mock, promoted their attachment, invasion, and directional movement. We further evaluated the contribution of the structural/compositional modifications in ECM-Sdc1 on carcinoma cell behavior. By microcontact printing of culture surfaces, we forced the Sdc1-negative fibroblasts to produce ECM with parallel fiber organization, mimicking the architecture observed in ECM-Sdc1. We found that the fiber topography governs carcinoma cell migration directionality. Conversely, an elevated fibronectin level in ECM-Sdc1 was responsible for the enhanced attachment of the breast carcinoma cells. These observations suggest that Sdc1 expression in breast carcinoma stromal fibroblasts promotes the assembly of an architecturally abnormal ECM that is permissive to breast carcinoma directional migration and invasion.