Expression of trefoil factor 3 is decreased in colorectal cancer.

In colorectal cancer (CRC), high expression of trefoil factor 3 (TFF3) is associated with tumor progression and reduced patient survival; however, bioinformatics analyses of public 'omics' databases show low TFF3 expression in CRCs as compared to normal tissues. Thus, we examined TFF3 expression in CRCs and matching normal tissues to evaluate its role in CRC progression. TFF3 gene expression was characterized using the bioinformatics portal UALCAN (http://ualcan.path.uab.edu). Tissue microarrays (TMAs) of archival CRC specimens (n=96) were immunostained with anti­human TFF3 antibodies. Immunohistochemical (IHC) staining intensity was semi­quantitatively scored. For this cohort, the median follow­up was 5.4 years. Associations between clinical and pathological variables were determined using Chi­square or Fisher's exact tests. Univariate disease­free survival was estimated by the Kaplan­Meier method. Omics data analyses by UALCAN showed downregulation of TFF3 expression in CRC relative to normal tissue at protein (χ2, P<0.0001) levels. There was a similar decreasing trend of TFF3 expression in the pathologic stages of the CRCs (RNA, χ2, P=0.88 and protein, χ2 P<0.0001). UALCAN data analysis showed that TFF3 exhibited 27% lower mRNA expression in tumors with mutant TP53 (P=0.007). Confirming the findings of omics analyses, IHC analysis of TMAs exhibited lower TFF3 expression in 95.6% (65 of 68) of the available normal­tumor matching pairs (χ2, P<0.0001). There was no statistically significant association of tumor TFF3 expression with patient sex, race/ethnicity, tumor location within the colorectum, Tumor, Node, Metastasis (TNM) stage, lymph node metastasis, or surgical margins. However, low TFF3 IHC staining in tumor tissue was associated with histological grade (P=0.026). Kaplan­Meier survival analysis showed no prognostic value of low TFF3 expression relative to those with high expression (log­rank, P=0.605). Our findings demonstrate low expression of TFF3 in CRCs. Association between low TFF3 and histopathological features suggests involvement of this molecule in progression of CRC.

Timing of surgery and the role of adjuvant radiotherapy in ewing sarcoma of the chest wall: a single-institution experience.

BACKGROUND: Ewing sarcoma (ES) is the most common chest wall malignancy in adolescents. Current therapy incorporates chemotherapy to treat systemic disease and radiotherapy to assist with local control. We sought to evaluate the timing of surgery and role of adjuvant radiotherapy. METHODS: We reviewed the St. Jude Children's Research Hospital chest wall ES experience from 1979 to 2009. Patient demographics, tumor characteristics, treatment variables, and outcomes were analyzed with respect to timing of surgery and use of adjuvant radiotherapy. RESULTS: Our cohort consisted of 36 patients with chest wall ES; median follow-up was 14.2 years, and 15-year estimate of overall survival was 66 %. In patients with localized disease, the timing of surgery (up-front vs. delayed) did not impact margin negativity or the use of adjuvant radiotherapy, but it did decrease the extent of chest wall resection. When considering radiotherapy in patients with localized disease, we found that patients who did not receive radiotherapy had smaller tumor size (median 6 vs. 10 cm) (p = 0.04) and were more likely to have had negative margins (p = 0.01) than patients who received adjuvant radiotherapy. One patient in each group developed a locoregional recurrence. The 15-year estimated of overall survival for patients who received adjuvant radiotherapy was 80 versus 100 % for those who did not. CONCLUSIONS: Delayed surgery decreased the extent of chest wall resection and helped define a patient population with favorable tumor biology. Patients with complete pathologic responses to chemotherapy, and those with tumors <8 cm and negative surgical margins may be spared adjuvant radiotherapy without any decrement in overall survival.

Analysis of prognostic factors in extraosseous Ewing sarcoma family of tumors: review of St. Jude Children's Research Hospital experience.

BACKGROUND: Advances in the treatment of Ewing sarcoma family of tumors (ESFT) are the result of improvements in systemic and local therapies. Clinical data of extraosseous ESFT are scarce. METHODS: A retrospective analysis of all patients with extraosseous ESFT treated at St. Jude Children's Research Hospital (SJCRH) from June 1982 to August 2009. RESULTS: Forty-six patients with extraosseous ESFT were identified. The mean age at diagnosis was 13.8 years. The majority of patients were male and white. The most common site of primary tumor was the trunk. Twelve patients had subcutaneous tumors. The median tumor size was 8 cm. Six patients (13 %) had metastatic disease at diagnosis. A total of 59 % of patients were alive at the time of analysis, with a median follow-up from diagnosis of 15.3 years. Fifteen-year estimates of survival and event-free survival (EFS) for all patients were 53.3 ± 9.4 and 50 ± 9.1 %, respectively. Fifteen-year estimates of survival and EFS with localized disease were 61.4 ± 9.8 and 57.6 ± 9.7 %, respectively. Stage and subcutaneous ESFT were significant predictors of outcome. There was no significant difference in patient's demographics and tumor characteristics between patients with skeletal ESFT and extraosseous Ewing sarcoma. The outcome for patients with localized extraosseous Ewing sarcoma was similar to that reported for all localized ESFT patients treated at SJCRH. CONCLUSIONS: The outcome for localized patients treated with extraosseous ESFT was similar to that reported for all ESFT patients treated on protocols at SJCRH. Patients with subcutaneous ESFT had a favorable prognosis when compared to their counterparts.