Associations of angiogenesis-related proteins with specific prognostic factors, breast cancer subtypes and survival outcome in early-stage breast cancer patients. A Hellenic Cooperative Oncology Group (HeCOG) trial.

Several studies support an important role of angiogenesis in breast cancer growth and metastasis. The main objectives of the study were to investigate the immunohistochemical expression of vascular endothelial growth factor (VEGF) family ligands (VEGF-A and VEGF-C) and receptors (VEGFR1, VEGFR2 and VEGFR3) in breast cancer and their associations with clinicopathological parameters, cancer subtypes/subgroups and patient outcome. Formalin-fixed paraffin-embedded tumor tissue samples were collected from early-stage breast cancer patients treated with anthracycline-based chemotherapy within a randomized trial. Immunohistochemistry was performed on serial 2.5 µm thick tissue sections from tissue microarray blocks. High VEGF-A, VEGF-C, VEGFR1, VEGFR2 and VEGFR3 protein expression was observed in 11.8% (N = 87), 80.8% (N = 585), 28.1% (N = 202), 64.6% (N = 359) and 71.8% (N = 517) of the cases, respectively. Significant associations were observed among all proteins (all p-values <0.05), with the exception of the one between VEGF-C and VEGFR1 (chi-square test, p = 0.15). Tumors with high VEGF-A protein expression, as compared to tumors with low expression were more frequently ER/PgR-negative (33.3% vs. 20.8%, chi-square test, p = 0.009) and HER2-positive (44.8% vs. 20.6%, p<0.001). In addition, tumors with high VEGFR1 expression, were more frequently HER2-positive (32.8% vs. 19.6%, p<0.001), while tumors with high VEGFR3 expression were more frequently ER/PgR-negative (24.9% vs. 17.0%, p = 0.024) and HER2-positive (26.9% vs. 14.8%, p = 0.001). High VEGF-A and VEGF-C protein expression was associated with increased DFS in the entire cohort (HR = 0.57, 95% CI 0.36-0.92, Wald's p = 0.020 and HR = 0.71, 95% CI 0.52-0.96, p = 0.025, respectively), as well as in specific subtypes/subgroups, such as HER2-positive (VEGF-A, HR = 0.32, 95% CI 0.14-0.74, p = 0.008) and triple-negative (VEGF-C, HR = 0.44, 95% CI 0.21-0.91, p = 0.027) patients. High vs. low VEGFR1 expression was an unfavorable factor for DFS in triple-negative patients (HR = 2.74, 95% CI 1.26-5.98, p = 0.011), whereas the opposite was observed among the ER/PgR-positive patients (HR = 0.69, 95% CI 0.48-0.98, p = 0.041). Regarding OS, high VEGF-C protein expression was associated with increased OS in the entire cohort (HR = 0.64, 95% CI 0.46-0.89, Wald's p = 0.008), as well as in in specific subtypes/subgroups, such as ER/PgR-negative (HR = 0.37, 95% CI 0.20-0.71, p = 0.003) and triple-negative (HR = 0.42, 95% CI 0.19-0.90, p = 0.026) patients. In conclusion, high expression of angiogenesis-related proteins is associated with adverse clinicopathological parameters in early-stage breast cancer patients and may be surrogate markers of biologically distinct subgroups of ER/PgR-negative or triple-negative tumors with superior outcome. Further validation of our findings in independent cohorts is needed.

Pure small cell carcinoma of the prostate: a case report and literature review.

Primary small cell carcinoma of the prostate (SCPCa) is a rare pathologic entity with unique clinical features and a poor prognosis. We present a case of a patient diagnosed with pure SCPCa treated with a combined chemo-radiotherapeutic approach. Pathological findings showed that the neoplastic cells exhibited positivity for pancytokeratin, synaptophysin, thyroid transcription factor-1 and CD56. Immunostaining for prostate-specific antigen was negative, while serum prostate-specific antigen was within normal limits. We review the available literature to gain additional information about diagnosis, treatment and prognosis of pure SCPCa.

Plexiform neurofibroma of the cauda equina: a case report and review of the literature.

Plexiform neurofibroma of the cauda equina is extremely rare. Herein, a case is reported in a 56-year-old man who also had muscle atrophy, severe motor disturbance, and mild sensory disturbance of the left leg due to childhood poliomyelitis. The clinical symptoms manifested insidiously until the patient developed cauda equina syndrome. At operation, the tumor mass was observed to engulf the nerve roots of the cauda equina. After pathological examination, the diagnosis of plexiform neurofibroma was made. Neither the patient described herein nor any previously reported patients had neurofibromatosis.

Important drug safety information on the internet: assessing its accuracy and reliability.

BACKGROUND: The Internet is becoming increasingly important as a source of health-related information, but the accuracy and reliability of information presented on the world wide web is debated. OBJECTIVE: We aimed to assess whether important, recent drug safety information is accurately reflected on Internet sites. METHODS: We evaluated whether major warnings issued by the US FDA between October 1, 2000 and September 30, 2001 on severe and life-threatening drug toxicity were mentioned 4-16 months later in the top ten web pages identified for these drugs by each of seven different search engines. We examined predictors of precise mention of the FDA warnings using logistic regressions. RESULTS: Twenty major safety warnings on 21 drugs (including three withdrawals) were eligible for the study. Among 519 different pertinent web pages retrieved (16-32 for each drug), precise mention of the safety issue was made in only 165 (31.8%). Best rates of precise mention were seen in web sites sponsored by attorneys (79.4%), in physician-oriented web pages (65.5%) and for withdrawn drugs (57.9%). In addition to these factors, better coverage of the FDA warnings was independently seen when no other adverse effects from the same organ system was mentioned (p < 0.001), while coverage was worse when there was no date on the site and web page (p = 0.020), and when the site owner could not be classified or was unknown (p = 0.014). CONCLUSIONS: Important safety warnings are inadequately covered in the majority of web pages. This deficiency creates a source of potentially harmful misinformation for health consumers.