Central compartment revision surgery for persistent or recurrent thyroid carcinoma: analysis of survival and complication rate.

PURPOSE: Locoregional recurrence of thyroid carcinoma is relatively common and reported rate are between 5 and 20%. Cervical nodes are usually involved, especially at the central compartment. The management of recurrent thyroid carcinoma at central compartment still remains challenging because of higher incidence of complication rate. The aim of the study is to evaluate the survival and complications rate after revision surgery. METHODS: Retrospective cohort study on a group of patients that underwent revision surgery for persistent or recurrent thyroid carcinoma from January 1, 2003 to December 31, 2017. Survival outcomes were calculated using Kaplan-Meier method. Significant variables on univariate analysis were subjected to a Cox proportional hazards regression multivariate model. RESULTS: Fifty-two patients involved, 22 male (40%) and 30 female (60%). Mean age was 54 years old (range 24-85). Mean follow-up was 79 months, median follow-up was 85 months, with a range between 8 and 153 months. The 5-year overall survival was 90.8% while at 10 years it was 69.8%. The 5-year disease-specific survival was 93.5%, while at 10 years it dropped to 77.9%. The rate of recurrent laryngeal nerve paralysis and persistent hypocalcemia in our series were 1.3% and 5.9%, respectively. No evidence of thoracic duct, esophageal or laryngeal and tracheal injury was found in this case series. Regarding prognostic factors, univariate and multivariate analysis highlighted as statistically significant: the aggressive histological variants, the presence extranodal extension or soft-tissue metastasis. CONCLUSION: The surgical option remains the gold standard in locoregional recurrences of thyroid carcinoma and should be performed by experienced surgeons to reduce postoperative complications.

Identification of cancer biomarkers of prognostic value using specific gene regulatory networks (GRN): a novel role of RAD51AP1 for ovarian and lung cancers.

To date, microarray analyses have led to the discovery of numerous individual 'molecular signatures' associated with specific cancers. However, there are serious limitations for the adoption of these multi-gene signatures in the clinical environment for diagnostic or prognostic testing as studies with more power need to be carried out. This may involve larger richer cohorts and more advanced analyses. In this study, we conduct analyses-based on gene regulatory network-to reveal distinct and common biomarkers across cancer types. Using microarray data of triple-negative and medullary breast, ovarian and lung cancers applied to a combination of glasso and Bayesian networks (BNs), we derived a unique network-containing genes that are uniquely involved: small proline-rich protein 1A (SPRR1A), follistatin like 1 (FSTL1), collagen type XII alpha 1 (COL12A1) and RAD51 associated protein 1 (RAD51AP1). RAD51AP1 and FSTL1 are significantly overexpressed in ovarian cancer patients but only RAD51AP1 is upregulated in lung cancer patients compared with healthy controls. The upregulation of RAD51AP1 was mirrored in the bloods of both ovarian and lung cancer patients, and Kaplan-Meier (KM) plots predicted poorer overall survival (OS) in patients with high expression of RAD51AP1. Suppression of RAD51AP1 by RNA interference reduced cell proliferation in vitro in ovarian (SKOV3) and lung (A549) cancer cells. This effect appears to be modulated by a decrease in the expression of mTOR-related genes and pro-metastatic candidate genes. Our data describe how an initial in silico approach can generate novel biomarkers that could potentially support current clinical practice and improve long-term outcomes.

Associations between RAD51D germline mutations and breast cancer risk and survival in BRCA1/2-negative breast cancers.

Background: RAD51D is involved in DNA double-strand break repair by homologous recombination and plays an important role in the maintenance of genomic stability. The associations between RAD51D germline mutations and breast cancer risk and survival are not fully elucidated. Patients and methods: RAD51D germline mutations were determined using a multigene panel in 7657 unselected breast cancer patients who were negative for BRCA1/2 germline mutations. The RAD51D recurrent mutation p.K91fs was screened in 7947 healthy controls by Sanger sequencing. Results: A total of 29 cases (0.38%) carried deleterious RAD51D germline mutations among this cohort of 7657 unselected breast cancer patients. The RAD51D recurrent mutation p.K91fs was identified in 18 cases (0.24%) of these 7657 patients. In contrast, the p.K91fs mutation was found in 8 of 7947 healthy controls with a frequency of 0.10%. The RAD51D p.K91fs mutation was significantly associated with increased breast cancer risk in unselected breast cancer [odds ratio = 2.34, 95% confidence interval (CI) 1.02-5.38; P = 0.040]. RAD51D mutation carriers were diagnosed at a younger age (P = 0.006) and were more likely to be triple-negative breast cancer (P = 0.003), estrogen receptor negative (P = 0.005) and high-grade cancers (P = 0.023) than noncarriers. Furthermore, RAD51D mutation carriers had a significantly worse recurrence-free survival [unadjusted hazard ratio (HR) = 3.00, 95% CI 1.56-5.80; P = 0.001] and distant recurrence-free survival (unadjusted HR = 2.54, 95% CI 1.14-5.67; P = 0.023) than noncarriers. Conclusion: The RAD51D recurrent mutation, p.K91fs, confers a moderately increased breast cancer risk, and RAD51D mutation carriers have an unfavorable survival compared with noncarriers.

Thyroid cancer: trends in incidence, mortality and clinical-pathological patterns in Zhejiang Province, Southeast China.

BACKGROUND: Thyroid cancer is the most common malignant disease of the endocrine system. Previous studies indicate a rapid increase in the incidence of thyroid cancer in recent decades, and this increase has aroused the great public concern. The aim of this study was to analyze the trends in incidence, mortality and clinical-pathological patterns of thyroid cancer in Zhejiang province. METHODS: Population-based incidence and mortality rates of thyroid cancer were collected from eight cancer registries in Zhejiang from 2000 to 2012. The incidence and mortality rates were age-standardized to Segi's world population. A Joinpoint model was used to examine secular trends in age-adjusted thyroid cancer rates with the Joinpoint Regression Program Version 4.0.0. Thyroid cancer patients were recruited from Zhejiang Cancer Hospital from 1972 to 2014. Patient demographics, tumor histology and tumor size were compared among the different periods of 1972-1985, 1986-1999 and 2000-2014. RESULTS: The age-standardized incidence rate of thyroid cancer in Zhejiang cancer registries was 2.75/105 in 2000, and increased to 19.42/105 in 2012. Additionally, we observed significantly increasing incidence rates with the Annual Percent Change (APC) of 22.86% (95%CI, 19.2%-26.7%). The age-standardized mortality of thyroid cancer in Zhejiang cancer registries was 0.23/105 in 2000 and 0.25/105 in 2012. No significant change in mortality rate was found. We observed a rapid increase in the proportions of papillary thyroid carcinoma (PTC) in 12,508 patients with thyroid carcinoma identified in the Zhejiang Cancer Hospital from 1972 to 2014 while the proportions of poorly differentiated thyroid cancer (PDTC), medullary thyroid carcinoma (MTC) and follicular thyroid carcinoma (FTC) decreased over the decades. In the PTC cases, the proportion of patients with maximum tumor diameter (MTD) < 1 cm dramatically and significantly increased from 0 in 1972-1985 to 32.1% in 2000-2014. CONCLUSIONS: A rapid increase in incidence and a stable trend in mortality of thyroid cancer were found in the distribution of thyroid cancer. Most of the increased incidence was PTC, especially the papillary thyroid microcarcinoma (PTMC) with MTD < 1 cm. This increase in incidence might be due to increased diagnosis with advanced technology.

Survival in patients with medullary thyroid cancer after less than the recommended initial operation.

BACKGROUND AND OBJECTIVES: We aimed to evaluate the disease specific-survival (DSS) of patients with Medullary Thyroid Cancer (MTC) confined to the central neck based on the extent of the initial operation. METHODS: This retrospective review of patients with MTC from the SEER registry from 2004 to 2012 excluded patients with lateral neck involvement or distant metastases. RESULTS: The cohort (n = 766) included 85(11%) less than total thyroidectomies (TT), 212(28%) TT alone, and 469(61%) TT with lymph node excision. Mean tumor size was similar (2.2cm for

Long-Term Outcome After Surgery for Medullary Thyroid Carcinoma: A Single-Center Experience.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a rare C cells-derived tumor, with a hardly predictable long-term prognosis. This study was aimed to evaluate the predictive factors of cure and survival after surgery for MTC in a monocentric series. METHODS: A retrospective analysis of the long-term outcomes was assessed in 255 MTC patients operated between 1980 and 2015 at Padua University hospital. RESULTS: Sporadic MTC occurred in 65.1% and hereditary MTC in 34.9% of patients. At a median follow-up of 93 months (range 7-430), the cure rate was 56.8%. The overall 10-year survival was 84.4%, and MTC-related death rate was 15.3%. Patients who died because of MTC had a median age of 61 years (range 21-84) and were at stages III-IV in all cases; deaths occurred in 18% of sporadic MTC, 6% of MEN2a and 66.7% of MEN2b patients. None of the patients at stages I-II died because of the disease, but 17.7% had persistent/recurrent disease. Based on univariate analysis, age, gender, genetic variant, extent and year of surgery, tumor size, lymph-nodal metastases and tumor stage significantly affected cure and survival rates. At multivariate analysis, only patient- and tumor-related features (age, lymph-nodal status and stage) remained significant independent prognostic factors. CONCLUSIONS: Radical surgery is the only chance of definitive cure in MTC, but it is possible only at early stage; in advanced stages, even extensive surgery could not grant cure and prolonged survival. Stage, nodal metastases and age remain the main predictive factors for cure and survival.

Overall survival analysis of EXAM, a phase III trial of cabozantinib in patients with radiographically progressive medullary thyroid carcinoma.

BACKGROUND: Primary analysis of the double-blind, phase III Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer (EXAM) trial demonstrated significant improvement in progression-free survival with cabozantinib versus placebo in patients with progressive medullary thyroid cancer (MTC). Final analysis of overall survival (OS), a key secondary endpoint, was carried out after long-term follow-up. PATIENTS AND METHODS: EXAM compared cabozantinib with placebo in 330 patients with documented radiographic progression of metastatic MTC. Patients were randomized (2:1) to cabozantinib (140 mg/day) or placebo. Final OS and updated safety data are reported. RESULTS: Minimum follow-up was 42 months. Kaplan-Meier analysis showed a 5.5-month increase in median OS with cabozantinib versus placebo (26.6 versus 21.1 months) although the difference did not reach statistical significance [stratified hazard ratio (HR), 0.85; 95% confidence interval (CI), 0.64-1.12; P = 0.24]. In an exploratory assessment of OS, progression-free survival, and objective response rate, cabozantinib appeared to have a larger treatment effect in patients with RET M918T mutation-positive tumors compared with patients not harboring this mutation. For patients with RET M918T-positive disease, median OS was 44.3 months for cabozantinib versus 18.9 months for placebo [HR, 0.60; 95% CI, 0.38-0.94; P = 0.03 (not adjusted for multiple subgroup analyses)], with corresponding values of 20.2 versus 21.5 months (HR, 1.12; 95% CI, 0.70-1.82; P = 0.63) in the RET M918T-negative subgroup. Median treatment duration was 10.8 months with cabozantinib and 3.4 months with placebo. The safety profile for cabozantinib remained consistent with that of the primary analysis. CONCLUSION: The secondary end point was not met in this final OS analysis from the trial of cabozantinib in patients with metastatic, radiographically progressive MTC. A statistically nonsignificant increase in OS was observed for cabozantinib compared with placebo. Exploratory analyses suggest that patients with RET M918T-positive tumors may experience a greater treatment benefit with cabozantinib. TRIAL REGISTRATION NUMBER: NCT00704730.

Management and outcomes of patients with renal medullary carcinoma: a multicentre collaborative study.

OBJECTIVE: To describe the management strategies and outcomes of patients with renal medullary carcinoma (RMC) and characterise predictors of overall survival (OS). PATIENTS AND METHODS: RMC is a rare and aggressive malignancy that afflicts young patients with sickle cell trait; there are limited data on management to date. This is a study of patients with RMC who were treated in 2000-2015 at eight academic institutions in North America and France. The Kaplan-Meier method was used to estimate OS, measured from initial RMC diagnosis to date of death. Cox regression analysis was used to determine predictors of OS. RESULTS: In all, 52 patients (37 males) were identified. The median (range) age at diagnosis was 28 (9-48) years and 49 patients (94%) had stage III/IV. The median OS for all patients was 13.0 months and 38 patients (75%) had nephrectomy. Patients who underwent nephrectomy had superior OS compared to patients who were treated with systemic therapy only (median OS 16.4 vs 7.0 months, P < 0.001). In all, 45 patients received chemotherapy and 13 (29%) had an objective response; 28 patients received targeted therapies, with 8-week median therapy duration and no objective responses. Only seven patients (13%) survived for >24 months. CONCLUSIONS: RMC carries a poor prognosis. Chemotherapy provides palliation and remains the mainstay of therapy, but <20% of patients survive for >24 months, underscoring the need to develop more effective therapy for this rare tumour. In this study, nephrectomy was associated with improved OS.

Renal medullary carcinoma: A national analysis of 159 patients.

BACKGROUND: Renal medullary carcinoma (RMC) is an aggressive malignancy seen predominantly in young males with sickle cell trait. RMC is poorly understood, with fewer than 220 cases described in the medical literature to date. We used a large national registry to define the typical presentation, treatments, and outcomes of this rare tumor. METHODS: The National Cancer Database was queried for patients under 40 years of age diagnosed with RMC from 1998 to 2011. An analysis of patient and tumor characteristics, treatment details, and overall survival (OS) was undertaken, and factors associated with mortality were identified using multivariable regression analysis. RESULTS: In total, 159 patients with RMC were identified, of whom a majority were male (71%), African American (87%), and had metastatic disease (71%). Median tumor size was 6 cm and median survival was 7.7 months. Most patients underwent surgery (60%) and chemotherapy (65%). Few patients received radiation (12%). Patients with metastatic disease had a significantly worse median survival (4.7 vs. 17.8 months, P < 0.001) and were less likely to receive surgery (42% vs. 91%, P < 0.001). Age and tumor size did not appear to impact OS. CONCLUSION: In the largest cohort to date of patients with RMC, we found a dismal median survival of less than 8 months. Age and tumor size were not associated with OS. Metastatic disease at presentation was the main negative prognostic indicator in RMC and was present in a majority of patients at the time of diagnosis.

Platinum plus bortezomib for the treatment of pediatric renal medullary carcinoma: Two cases.

Renal medullary carcinoma (RMC) was first described over two decades ago as the seventh sickle nephropathy. Survival after diagnosis with metastatic disease still rarely extends beyond 1 year, with recent reports of median overall survival in patients treated with platinum therapy being just 10 months. We describe our experience using platinum-based chemotherapy plus the proteasome inhibitor bortezomib to treat metastatic RMC in two pediatric patients who had complete responses. One patient passed away 7 years after diagnosis, while another remains disease free nearly 2 years from diagnosis.

First report on molecular breast cancer subtypes and their clinico-pathological characteristics in Eastern Morocco: series of 2260 cases.

BACKGROUND: Breast cancer is the most frequent malignancy among women in Eastern Morocco. In this paper, we provide the first report on molecular breast cancer subtypes in this region. This is the largest population-based study on breast cancer among Moroccan women. METHODS: We analyzed 2260 breast cancer cases diagnosed at the Hassan II Regional Oncology Center between October 2005 and December 2012. Clinico-pathological and therapeutic features were studied. Molecular subtypes were determined and their associations with the clinico-pathological characteristics of the tumors were examined. RESULTS: The mean age at diagnosis was 48.7 years ±11.4. Invasive ductal carcinoma was the predominant histological type (77.1%), followed by lobular invasive carcinoma (15.3%). The mean size of breast tumors was 3.5 cm ± 1.96, and 84% of our patients are diagnosed with tumors of more than 2 cm. Histological grade II tumors were the most frequent (70.4%), followed by advanced histological grade (18%). Lymph node positive tumors were observed in 64.8% of cases and 29.3% of patients had distant metastasis. Most tumors were hormone receptor-positive (73%) and 28.6% were HER2 positive. 86.1% of patients with hormone receptor-positive breast cancer were given hormone therapy, while 68.9% of patients with HER2+ breast cancer received targeted therapy with Herceptin. Luminal A was the commonest molecular subtype, followed by Luminal B, Triple Negative and HER2. The highest prevalence of premenopausal patients was observed in Triple Negative subtype (72.2%), followed by HER2 (64.1%), Luminal B (62.2%), and Luminal A (55.1%). Luminal B subtype had a poorer prognosis than Luminal A. Compared with Triple Negative, HER2 subtype tend to spread more aggressively and is associated with poorer prognosis. CONCLUSIONS: Unlike Western countries, breast cancer occurs at an earlier age and is diagnosed at a more advanced stage in Eastern Morocco. In this region, hormone receptor-positive tumors are predominant and so the majority of breast cancer patients should benefit from hormone therapy. HER2 subtype presents an aggressive tendency, suggesting the importance of anti-HER2 therapy. This study will contribute in developing appropriate screening and cancer management strategies in Eastern Morocco.

Atypical medullary carcinoma of the breast has similar prognostic factors and survival to typical medullary breast carcinoma: 3,976 cases from the National Cancer Data Base.

BACKGROUNDS AND OBJECTIVES: Medullary breast carcinoma (MBC) is a subtype with a more favorable prognosis. Tumors with some, but not all, characteristics of MBC are classified as atypical medullary carcinoma of the breast (AMCB). METHODS: Patients with invasive MBC and AMCB reported to the National Cancer Data Base (NCDB) from 2004 to 2013 were compared for tumor characteristics and overall survival, using infiltrating ductal carcinoma (IDC) as a reference. RESULTS: Patients with MBC (n = 3,688), AMCB (n = 288), and IDC (n = 918,870) met inclusion criteria. Comparing MBC with AMCB, the mean age at diagnosis (52.9 vs. 53.9 years), mean tumor size (2.4 vs. 2.5 cm), lymph node positivity (22.8% vs. 22.4%), estrogen receptor (ER) positivity (22% vs. 25%), progesterone receptor (PR) positivity (14% vs. 15%), HER2 positivity (11% vs. 14%), rate of breast conserving surgery (67% vs. 68%), use of chemotherapy (76% vs. 75%), and use of hormonal therapy (19% vs. 18%), respectively, were not clinically or statistically different. Five-year (92% vs. 89%) and 10-year survival rates (85% vs. 87%) were not significantly different (P = 0.46). CONCLUSIONS: There does not appear to be any reason to differentiate between AMCB and MBC given the similarities in presentation, treatment and prognosis. J. Surg. Oncol. 2016;114:533-536. © 2016 Wiley Periodicals, Inc.

Lymph node metastases and elevated postoperative calcitonin: Predictors of poor survival in medullary thyroid carcinoma.

Background Total thyroidectomy is the treatment of choice for medullary thyroid carcinoma (MTC), but the extent of neck dissection is controversial. Lymph node metastases, distant metastases, and old age are known predictors of poor survival. Patients Patients treated for primary MTC at Helsinki University Hospital from 1990 to 2009 were included (n = 54). Their clinical characteristics, treatment, and outcome were analysed retrospectively, these patients were followed until death or their last follow-up date. Results At last follow-up (3.4-23 years), of 54 MTC patients, 19 (35%) were disease-free, 17 (32%) were alive with disease, and 12 (22%) had died of MTC; six patients died of unrelated causes (11%). All disease-free patients were node negative and had normal postoperative calcitonin level. Of 19 disease-free patients, only four (21%) had undergone lymph node dissection. All patients who died of MTC were Stage IV at diagnosis and died with distant metastases. Disease-specific five-and 10-year survival was 84% and 76.2%. Advanced T-stage (p = 0.004), lymph node metastases (p < 0.001), distant metastases (p < 0.001), stage (p < 0.001), and elevated postoperative calcitonin (p < 0.001) significantly associated with survival. Conclusions Lymph node metastasis and elevated postoperative calcitonin are important prognostic factors. Patients with lymph node metastasis and/or elevated postoperative calcitonin with present treatments cannot become disease-free, but most of them can live a long life with metastasis.

Disease-free survival after complete mesocolic excision compared with conventional colon cancer surgery: a retrospective, population-based study.

BACKGROUND: Application of the principles of total mesorectal excision to colon cancer by undertaking complete mesocolic excision (CME) has been proposed to improve oncological outcomes. We aimed to investigate whether implementation of CME improved disease-free survival compared with conventional colon resection. METHODS: Data for all patients who underwent elective resection for Union for International Cancer Control (UICC) stage I-III colon adenocarcinomas in the Capital Region of Denmark between June 1, 2008, and Dec 31, 2011, were retrieved for this population-based study. The CME group consisted of patients who underwent CME surgery in a centre validated to perform such surgery; the control group consisted of patients undergoing conventional colon resection in three other hospitals. Data were collected from the Danish Colorectal Cancer Group (DCCG) database and medical charts. Patients were excluded if they had stage IV disease, metachronous colorectal cancer, rectal cancer (≤ 15 cm from anal verge) in the absence of synchronous colon adenocarcinoma, tumour of the appendix, or R2 resections. Survival data were collected on Nov 13, 2014, from the DCCG database, which is continuously updated by the National Central Office of Civil Registration. FINDINGS: The CME group consisted of 364 patients and the non-CME group consisted of 1031 patients. For all patients, 4-year disease-free survival was 85.8% (95% CI 81.4-90.1) after CME and 75.9% (72.2-79.7) after non-CME surgery (log-rank p=0.0010). 4-year disease-free survival for patients with UICC stage I disease in the CME group was 100% compared with 89.8% (83.1-96.6) in the non-CME group (log-rank p=0.046). For patients with UICC stage II disease, 4-year disease-free survival was 91.9% (95% CI 87.2-96.6) in the CME group compared with 77.9% (71.6-84.1) in the non-CME group (log-rank p=0.0033), and for patients with UICC stage III disease, it was 73.5% (63.6-83.5) in the CME group compared with 67.5% (61.8-73.2) in the non-CME group (log-rank p=0.13). Multivariable Cox regression showed that CME surgery was a significant, independent predictive factor for higher disease-free survival for all patients (hazard ratio 0.59, 95% CI 0.42-0.83), and also for patients with UICC stage II (0.44, 0.23-0.86) and stage III disease (0.64, 0.42-1.00). After propensity score matching, disease-free survival was significantly higher after CME, irrespective of UICC stage, with 4-year disease-free survival of 85.8% (95% CI 81.4-90.1) after CME and 73.4% (66.2-80.6) after non-CME (log-rank p=0·0014). INTERPRETATION: Our data indicate that CME surgery is associated with better disease-free survival than is conventional colon cancer resection for patients with stage I-III colon adenocarcinoma. Implementation of CME surgery might improve outcomes for patients with colon cancer. FUNDING: Tvergaards Fund and Edgar and Hustru Gilberte Schnohrs Fund.

Medullary colorectal carcinoma revisited: a clinical and pathological study of 102 cases.

AIM: Medullary carcinoma is a recently described subtype of mismatch repair deficient (MMRd) colorectal carcinoma (CRC) which, despite being poorly differentiated by traditional morphological criteria, has been reported to have a good prognosis. We investigated the pathological and clinical features of medullary CRC in an unselected cohort of CRCs undergoing surgical resection. METHODS: All CRCs resected within a single health district database from 1998 to 2012 were categorized prospectively and underwent retrospective review to identify 91 medullary CRCs, with 11 additional cases from 2013 to 2014. Strict criteria were employed to diagnose medullary carcinoma requiring both MMRd and greater than 90 % of the tumor to demonstrate typical morphology, including solid growth. The demographic and pathological features, as well as all-cause survival, were compared with other CRCs, and specifically to other MMRd CRCs. RESULTS: From 1998 to 2012, 91 of 3,295 CRCs (2.8 %) were of the medullary type. Medullary CRC was more likely to arise in females than males (3.3:1; p < 0.0001), the elderly (mean age 77 vs. 71 years; p < 0.001), and the right colon (86 %; p < 0.0001). All medullary CRCs demonstrated MMR deficiency (considered an inclusion criteria) and 86 % were BRAFV600E-mutated (p < 0.0001). Thirty-day mortality after resection was higher in medullary CRC (4.6 vs. 1.7 %; p = 0.049). On univariate analysis, survival was not better than well-differentiated or other MMRd tumors. However, using a multivariate model, a medullary phenotype was protective (hazard ratio of death 0.54, 95 % CI 0.30-0.96; p = 0.037). CONCLUSIONS: Medullary CRC is more common than previously reported, frequently presents with locally advanced disease, and may be associated with higher mortality at 30 days after resection. Despite this, when strict criteria are used for diagnosis, the overall survival is favorable when compared with CRCs with equivalent demographic and pathological characteristics.

Androgen receptor expression predicts decreased survival in early stage triple-negative breast cancer.

BACKGROUND: A subset of triple-negative breast cancer (TNBC) has been reported to express androgen receptor (AR); however, the clinical significance of AR expression in TNBC is unclear. METHODS: We examined immunohistochemical expression of AR in a large cohort of TNBC cases and correlated its expression with clinicopathologic features and clinical outcome. RESULTS: AR expression was found in 17.7% (87/492) of TNBCs. Positive expression of AR showed significant correlation with older age (p < 0.001), apocrine histology (p = 0.001), and lower histologic grade (p < 0.001). AR was a poor prognostic marker for overall survival (OS) in univariate (p = 0.026) and multivariate (p = 0.008) analyses. In the lymph node-negative (n = 316) subgroup, AR expression was a significant predictor of worse OS and disease-free survival (DFS) in both univariate (p = 0.028 and 0.011) and multivariate (p = 0.024 and 0.01, respectively) analyses. AR expression also was a prognostic factor in pT1 subgroup (OS, p = 0.007; DFS, p = 0.01); however, its prognostic value was not observed in TNBC patients with lymph node metastasis or tumor size larger than pT1. CONCLUSIONS: AR-expressing TNBCs represent a distinct breast cancer subgroup with adverse clinical outcome and AR blockade could be a potential endocrine therapy for these TNBC patients. Evaluation of AR status may provide additional information on prognosis and treatment in patients with TNBC.

Elevated expression of CCAT2 is associated with poor prognosis in esophageal squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: CCAT2, a novel long non-coding RNAs (lncRNAs), is found to promote the metastasis and invasion of colon, lung, and breast cancers. This study aimed to investigate the level of CCAT2 in esophageal squamous cell carcinoma (ESCC) and to elucidate its clinical significance. METHODS: The expression level of CCAT2 and the status of MYC amplification were examined in 229 ESCC samples using quantitative real- time PCR. RESULTS: CCAT2 was upregulated in ESCC tissues, especially in cases with lymph node metastasis (LNM), advanced TNM stages, and MYC amplification. Furthermore, the level of CCAT2 was positively correlated with TNM stages, LNM, and the number of positive lymph nodes. High CCAT2 expression and MYC amplification were significantly associated with TNM stages and LNM. Survival analyses revealed that high CCAT2 expression and MYC amplification were significantly associated with poorer overall survival in ESCC patients. Furthermore, patients with high CCAT2 expression and MYC amplification had a 2.199-fold increased risk of death compared with those with low CCAT2 expression and MYC non-amplification. CONCLUSIONS: Our study provides the first evidence associating CCAT2 expression and poor survival in ESCC. CCAT2 may be a prognostic biomarker and therapeutic target for ESCC.

Association between axillary lymph node status and Ki67 labeling index in triple-negative medullary breast carcinoma.

OBJECTIVE: Medullary breast carcinoma is a rare breast carcinoma with good prognosis. Although it has been established that axillary lymph node metastasis is a poor prognostic factor, little is known about the relationship between axillary lymph node metastasis and clinicopathological characteristics of medullary breast carcinoma patients. The aim of this study was to identify factors that predict occurrence of axillary lymph node metastasis in medullary breast carcinoma patients. METHODS: We performed a retrospective study of axillary lymph node status and the relevant clinicopathological characteristics in 49 triple-negative medullary breast carcinoma patients with axillary lymph node dissection between November 2004 and July 2011. RESULTS: A total of 49 patients were enrolled in the study. Fourteen patients (28.6%) had axillary lymph node metastasis that was confirmed pathologically. Axillary lymph node metastasis was not associated with age, menopausal status, primary tumor size or its location, the degree of inflammation within the tumor or mitotic count. However, we found a statistically significant association between axillary lymph node metastasis and Ki67 labeling index in primary tumors (P < 0.001). CONCLUSIONS: There is a positive association between Ki67 labeling index in the primary tumor and axillary lymph node metastasis in triple-negative medullary breast carcinoma patients.

Low prognostic implication of fibroblast growth factor family activation in triple-negative breast cancer subsets.

BACKGROUND: Despite a greater understanding of the molecular heterogeneity of breast cancer, current therapeutic strategies still cannot overcome the relatively poor prognosis of triple-negative breast cancer (TNBC). Deregulation of fibroblast growth factor (FGF) signaling has been found in breast cancer, and blocking this pathway has been suggested as a potential therapeutic target. We therefore evaluated the expression and copy number changes of FGF family members in TNBC. METHODS: We retrospectively evaluated 148 primary TNBC in 2009 for FGFR1, FGFR2, and FGF2 expression by immunohistochemistry. FGFR1 and FGFR2 gene copy numbers were analyzed by fluorescence in situ hybridization. The Cancer Genome Atlas (TCGA) data was used to study correlations between gene expression and amplification or methylation of FGFR1, FGFR2, and FGF2 in basal-like TNBC. RESULTS: FGFR1, FGFR2, and FGF2 expression were found in 16.2 % (24 of 148), 12.8 % (19 of 148), and 12.8 % (19 of 148) of TNBCs, respectively. FGFR1 gene amplification was observed in 4.1 % (6 of 145), and FGFR1 high polysomy was detected in 6.9 % (10 of 145) of the cases examined. FGFR2 gene amplification and high polysomy were identified in 4.7 % (6 of 129 cases) and 0.8 % (1 of 129 cases), respectively. FGF2 expression was found to be associated with basal-like TNBC. The expression of FGF family members and FGFR1 or FGFR2 gene amplification did not affect patient survival. TCGA data revealed that promoter methylation of the 3 genes was significantly associated with mRNA expression. CONCLUSIONS: Even though the implications for patient outcomes are not significant, subsets of TNBCs harbor FGFR1 or FGFR2 gene amplification and FGFR1, FGFR2, or FGF2 protein overexpression.

Relationship between IL-10 expression and prognosis in patients with primary breast cancer.

This retrospective study was designed to investigate the relationship between the expression of IL-10, CD4, CD8, and FOXP3 and clinicopathological features and prognosis in breast cancer patients. The expression of IL-10, CD4, CD8, and FOXP3 was detected by immunohistochemistry. Staining intensity of only IL-10 was associated with disease-free survival and distance disease-free survival (P<0.05). Staining density of IL-10 in stromal cells was associated with overall survival and distance disease-free survival (P<0.05). IL-10 expression levels might be used as a prognostic indicator for the recurrence, metastasis, and survival of breast cancer patients.