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Recently, studies have been focused on single nucleotide polymorphisms (SNPs) in matrix metalloproteinases 2 (MMP-2 C-1306T) and 9 (MMP-9 C-1562T) promoter regions and its role as a risk factor for cancer development.Concerning to breast cancer and MMP-2 C-1306 T, two studies were reported so far. Zhou et al., in China, showed that T alelle carries have a diminished risk of cancer development [1]. However, no association was detected among genotypes, TNM stage and estrogen receptor (ER) status [1]. On the other hand, Grieu et al., in a case-series of Caucasian individuals, in Australia, showed significant association between TT genotype and small and ER negative tumors [2]. In the same sample TT homozygous patients with ER negative tumors had poor survival rates (P < 0.001) [2].Regarding to MMP-9 C-1562T and carcinogenesis there are few information. Grieu et al.' study showed evidence of a probable association between the presence of the T allele and good prognosis (P = 0.06) [2]. In this case-series, T allele was associated with nonductal type histology, positive ER status and lack of TP53 mutation (P < 0.05) [2]. Przybylowska et al. [3] recently reported lack of association among MMP-9 C-1562T, breast cancer risk and the level of MMP-9 in tumor samples.Porto Alegre (South Brazil) has the highest breast cancer incidence and mortality of the country. The no association with breast cancer risk, neither with clinicopathological features in a South Brazilian population of high incidence of breast cancer.

-Medulloblastoma (MB) is the most common malignant brain tumor in childhood. The alterations found include: presence of oncoproteins p53 and HER2, elevated mitotic index, and presence of neuronal differentiation. The aim of this study was to determine the immunohistochemical expression of markers Ki-67, NeuN, synaptophysin, HER2 and p53 in 40 MB samples and their correlation with clinicopathologic parameters and survival. In 29 patients (72.5%), ≥20% of cells were positive for Ki-67. Males showed greater ki-67 expression (p=0.02) and smaller survival rates (p=0.002). NeuN and synaptophysin were negative in 16 (40%) and 8 (20%) cases, respectively. P53 was positive in 18 (45%) cases, with 11 (61%) weakly positive and 7 (39%) strongly positive. HER2 was positive in 23 (57.5%) of the samples and did not show statistical association with survival (p=0.07).KEy woRds: medulloblastoma, immunohistochemistry, Ki-67, NeuN, synaptophysin, HER2, p53, survival analysis. expressão imunoistoquímica dos marcadores ki-67, neun, sinaptofisina, p53 e her2 em meduloblastoma e sua correlação com os parâmetros clínico-patológicosResumo -Meduloblastoma (MB) é o tumor maligno encefálico mais freqüente na infância. dentre as alterações encontradas estão: a presença das oncoproteínas p53 e HER2, elevado índice mitótico e presença de diferenciação neuronal. o objetivo deste estudo foi determinar a expressão imunoistoquímica (IMQ) dos marcadores Ki-67, NeuN, sinaptofisina, HER2 e p53 em 40 amostras de MB, correlacionando-as com parâmetros clinicopatológicos e com a sobrevida. Vinte e nove pacientes (72,5%) apresentaram 20% ou mais das células positivas para Ki-67. os pacientes do sexo masculino apresentaram maior expressão do Ki-67 (p=0,02) e também menor sobrevida (p=0,002). NeuN e sinaptofisina foram negativos em 16 (40%) e 8 (20%) casos, respectivamente. P53 foi positivo em 18 (45%) casos, sendo 11 (61%) fracamente positivos e 7 (39%) fortemente positivos. HER2 foi positivo em 23 (57,5%) das amostras e não demonstrou associação estatística com a sobrevida (p=0.07).PAlAVRAs-cHAVE: meduloblastoma, imunoistoquímica, Ki-67, NeuN, sinaptofisina, HER2, p53, sobrevida. Medulloblastoma (MB) is the most common malignant brain tumor in children, accounting for about 20% of all primary tumors of the central nervous system (cNs), with a peak of incidence at 5-7 years-old. These tumors have an aggressive behavior and despite treatment, the 5-year survival rate is 60% 1,2 . For therapeutic and prognostic purposes, patients are divided in groups of high and low risk, according to the staging proposed by chang et al. (1969) 3 , age at the time of diagnosis, and presence of residual tumor 4,5 . A more accurate assessment of risk in children with MB can be done using a combination of clinical, histopathologic, and molecular prognostic factors 4,6,7 .

Cancer stem cells (CSCs) residing in colorectal cancer tissues have tumorigenic capacity and contribute to chemotherapeutic resistance and disease relapse. It is well known that the survival of colorectal CSCs after 5-fluorouracil (5-FU)-based therapy leads to cancer recurrence. Thus CSCs represent a promising drug target. Here, we designed and synthesized novel hybrid molecules linking 5-FU with the plant-derived compound thymoquinone (TQ) and tested the potential of individual compounds and their combination to eliminate colorectal CSCs. Both, Combi and SARB hybrid showed augmented cytotoxicity against colorectal cancer cells, but were non-toxic to organoids prepared from healthy murine small intestine. NanoString analysis revealed a unique signature of deregulated gene expression in response to the combination of TQ and 5-FU (Combi) and SARB treatment. Importantly, two principle stem cell regulatory pathways WNT/ß-Catenin and PI3K/AKT were found to be downregulated after Combi and hybrid treatment. Furthermore, both treatments strikingly eliminated CD133+ CSC population, accompanying the depleted self-renewal capacity by eradicating long-term propagated 3D tumor cell spheres at sub-toxic doses. In vivo xenografts on chicken eggs of SARB-treated HCT116 cells showed a prominent nuclear ß-Catenin and E-cadherin staining. This was in line with the reduced transcriptional activity of ß-Catenin and diminished cell adhesion under SARB exposure. In contrast to 5-FU, both, Combi and SARB treatment effectively reduced the angiogenic capacity of the remaining resistant tumor cells. Taken together, combination or hybridization of single compounds target simultaneously a broader spectrum of oncogenic pathways leading to an effective eradication of colorectal cancer cells.

MYC amplification is a frequent event in SCLC and is related to a short survival time. MYC amplification may be an independent prognostic factor for SCLC. Further studies are required to support this finding and clarify the role of MYC in SCLC tumorigenesis.

Our method showed good sensitivity/specificity to indicate the outcome of patients according to their cofilin immunocontent in biological samples. Its application in a retrospective cohort and the results presented here are an important step toward the validation process of cofilin-1 as a prognostic biomarker.

Purpose Enhancer of zeste homolog 2 (EZH2) is associated with epigenetic gene silencing and aggressiveness in many tumor types. However, the prognostic impact of high EZH2 expression is controversially discussed for colorectal cancer. For this reason, we immunohistochemically analyzed EZH2 expression in 105 specimens from colon cancer patients separately for tumor center and invasion front. Methods All sections from tissue microarrays were evaluated manually and digitally using Definiens Tissue Studio software (TSS). To mirror-image the EZH2 status at the tumor invasion front, we treated HCT116 colon cancer cells with the EZH2 inhibitor 3-Deazaneplanocin A (DZNep) and studied the growth of in ovo xenografts in the chorioallantoic membrane (CAM) assay. Results We showed a significant decrease in EZH2 expression and the repressive H3K27me3 code at the tumor invasion front as supported by the TSS-constructed heatmaps. Loss of EZH2 at tumor invasion front, but not in tumor center was correlated with unfavorable prognosis and more advanced tumor stages. The observed cell cycle arrest in vitro and in vivo was associated with higher tumor aggressiveness. Xenografts formed by DZNep-treated HCT116 cells showed loosely packed tumor masses, infiltrative growth into the CAM, and high vessel density. Conclusion The differences in EZH2 expression between tumor center and invasion front as well as different scoring and cutoff values can most likely explain controversial literature data concerning the prognostic value of EZH2. Epigenetic therapies using EZH2 inhibitors have to be carefully evaluated for each specific tumor type, since alterations in cell differentiation might lead to unfavorable results. Electronic supplementary material The online version of this article (10.1007/s00432-019-02977-1) contains supplementary material, which is available to authorized users.

Primary epidermoid carcinoma of the breast presenting as a breast abscess and sepsisresUMo CONTEXTO: O carcinoma de células escamosas da mama é um câncer extremamente raro, representando cerca de 0,04% dos tumores malignos da mama. Até o momento, apenas um número limitado de casos da doença foi relatado, a maioria se apresentando clinicamente como um carcinoma de mama usual. RELATO DE CASO: Paciente feminina de 39 anos de idade se apresentando com grande abscesso de mama e sinais de sepse. Após debridamento cirúrgico da lesão, o exame histopatológico da cápsula do abscesso revelou a presença de carcinoma de células escamosas da mama. O tratamento definitivo do tumor foi uma mastectomia radical modificada com ressecção da lesão residual na mama direita. CONCLUSÃO: O presente caso, de apresentação incomum, demonstra como uma lesão aparentemente benigna, como um abscesso mamário, pode estar relacionada a uma neoplasia maligna oculta. Uma revisão da literatura a respeito do carcinoma de células escamosas de mama é apresentada.I MD, PhD. Attending Physician,