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Tumor heterogeneity plays a key role in cancer relapse and metastasis, however, the distinct cellular behaviors and kinetics of interactions among different cancer cell subclones and the tumor microenvironment are poorly understood. By profiling an isogenic model that resembles spontaneous human ovarian cancer metastasis with an highly metastatic (HM) and non‐metastatic (NM) tumor cell pair, one finds an upregulation of Wnt/β‐catenin signaling uniquely in HM. Using humanized immunocompetent mice, one shows for the first time that activated β‐catenin acts nonautonomously to modulate the immune microenvironment by enhancing infiltrating tumor‐associated macrophages (TAM) at the metastatic site. Single‐cell time‐lapse microscopy further reveals that upon contact with macrophages, a significant subset of HM, but not NM, becomes polyploid, a phenotype pivotal for tumor aggressiveness and therapy resistance. Moreover, HM, but not NM, polarizes macrophages to a TAM phenotype. Mechanistically, β‐catenin upregulates cancer cell surface metadherin, which communicates through CEACAM1 expressed on macrophages to produce CCL3. Tumor xenografts in humanized mice and clinical patient samples both corroborate the relevance of enhanced metastasis, TAM activation, and polyploidy in vivo. The results thus suggest that targeting the β‐catenin‐metadherin/CEACAM1‐CCL3 positive feedback cascade holds great therapeutic potential to disrupt polyploidization of the cancer subclones that drive metastasis. [ABSTRACT FROM AUTHOR]

Aims Uterine leiomyosarcomas frequently show p16 immunoexpression. However, p16 may also be expressed in some benign leiomyoma variants such as leiomyomas with bizarre nuclei and cellular leiomyomas, limiting its utility as a biomarker to distinguish between benign and malignant neoplasms. We investigated p16 expression in leiomyomas with infarct-type necrosis, tumours which may sometimes be misinterpreted as smooth muscle tumours of uncertain malignant potential or even leiomyosarcoma on conventional light microscopy. Methods and results p16 immunostaining was performed on 35 leiomyomas with infarct-type necrosis and the staining pattern was analysed. Staining was classified as absent, scattered/isolated, <33-, 33-66- or >66%-positive cells, and was assessed in the areas immediately surrounding and distant from the infarct. The median age of patients was 44 years. Seventeen had hormonal/non-hormonal drugs and three were pregnant. The median tumour size was 7.25 cm. The mean mitotic count was 0.9/10 high-power fields. Only one tumour had multifocal mild nuclear atypia. Positive p16 was noted in 34 of 35 (97.2%) tumours. It was typically patchy, and was concentrated in areas immediately surrounding the necrosis. Distant from the necrosis, p16 positivity was seen predominantly in scattered/isolated cells. One tumour without any worrisome microscopic features showed diffuse p16 positivity throughout. Median follow-up was 55 months, and none of the patients experienced any recurrence. Conclusion p16 expression in benign uterine smooth muscle tumours with infarct-type necrosis is common. The staining is particularly concentrated adjacent to areas of necrosis. It is important to be aware of this potential pitfall when interpreting p16 expression. [ABSTRACT FROM AUTHOR]

A total of 16 cases of congenital fibrosarcoma have been reported from 1975 to March 2015. Five of the 16 had abnormal fusion between erythroblast transformation specific translocation variant 6 and neurotrophin recptor gene neurotrophic tyrosine kinase, receptor, type 3 ( ETV6- NTRK3); in another five out of 16 this was absent, and six were not tested. All were managed by surgical resection but none involved metastasis. Herein we report the case of a newborn baby girl with congenital fibrosarcoma negative for ETV6- NTRK3 gene fusion, who presented with ileal perforation and positive resection margin. She had rapid recurrence with lymph node metastasis treated with postoperative chemotherapy. There was no further recurrence at >3 years of follow up. [ABSTRACT FROM AUTHOR]

Aim Studies comparing the efficacy of radiofrequency ablation ( RFA) in terms of overall survival, disease-free survival and local recurrence in recurrent hepatocellular carcinoma ( HCC) are limited. We carried out the present study to compare the survival of recurrent HCC after RFA with that of first-occurrence HCC. Patients and Methods A total of 170 patients with HCC smaller than 5 cm who received RFA in a tertiary academic hospital were recruited. Clinical data were prospectively collected, reviewed and compared between recurrent and first-occurrence HCC groups. Patients who received RFA for post-ablation recurrent HCC were excluded. Results There was no significant difference in the complication, incomplete ablation, recurrence and survival rates between the recurrent HCC and the first-occurrence HCC groups. The tumour size in the recurrent HCC group was significantly smaller than that in the first-occurrence group (1.8 vs 2.5 cm), and the recurrent HCC group had a significantly higher proportion of Child's A cirrhosis. Conclusions When detected and treated early, the overall survival of recurrent HCC treated RFA was comparable to that of first-occurrence HCC. The advantages of RFA, especially when percutaneous route is feasible, over hepatectomy should be extended to recurrent HCC in suitable cases. [ABSTRACT FROM AUTHOR]

Background Radiofrequency ablation (RFA) has been used to treat hepatocellular carcinoma ( HCC) and liver metastases for more than 10 years with promising early outcomes. Preliminary results comparing percutaneous and surgical approaches have shown no difference in short-term outcomes. In this study, the longer-term outcomes were presented. Methods Patients with liver malignancies treated by RFA were prospectively studied from 2003 to 2011. Post-ablation assessment by computed tomography ( CT) scan and serum biochemistry was performed at regular intervals. Recurrence rates and long-term survival were analysed. Results A total of 233 patients with liver malignancies (75.5% HCC and 24.5% liver metastases) were analysed. Three RFA approaches were used (percutaneous 58.4%, laparoscopic 9.4% and open 32.2%). The median follow-up time was 29 months. Complete ablation was achieved in 83.7%, with no difference between the two approaches. More wound and chest complications were observed in the surgical group. Intra-hepatic recurrences were observed in 69.5%; extra-hepatic recurrences were detected in 22.3%, with no difference between the two groups. There was no statistical difference between the two approaches in overall 1-, 3- and 5-year survival. Conclusion An extended period of follow-up in patients with liver malignancies showed that RFA is an effective treatment. No difference was demonstrated between the percutaneous and surgical approach, in terms of recurrence and survival. [ABSTRACT FROM AUTHOR]