RESUMO
Breast cancer is characterized by oncobiosis, the abnormal composition of the microbiome in neoplastic diseases. The biosynthetic capacity of the oncobiotic flora in breast cancer is suppressed, as suggested by metagenomic studies. The microbiome synthesizes a set of cytostatic and antimetastatic metabolites that are downregulated in breast cancer, including cadaverine, a microbiome metabolite with cytostatic properties. We set out to assess how the protein expression of constitutive lysine decarboxylase (LdcC), a key enzyme for cadaverine production, changes in the feces of human breast cancer patients (n = 35). We found that the fecal expression of Escherichia coli LdcC is downregulated in lobular cases as compared to invasive carcinoma of no special type (NST) cases. Lobular breast carcinoma is characterized by low or absent expression of E-cadherin. Fecal E. coli LdcC protein expression is downregulated in E-cadherin negative breast cancer cases as compared to positive ones. Receiver operating characteristic (ROC) analysis of LdcC expression in lobular and NST cases revealed that fecal E. coli LdcC protein expression might have predictive values. These data suggest that the oncobiotic transformation of the microbiome indeed leads to the downregulation of the production of cytostatic and antimetastatic metabolites. In E-cadherin negative lobular carcinoma that has a higher potential for metastasis formation, the protein levels of enzymes producing antimetastatic metabolites are downregulated. This finding represents a new route that renders lobular cases permissive for metastasis formation. Furthermore, our findings underline the role of oncobiosis in regulating metastasis formation in breast cancer.
RESUMO
Although tumour recurrence is an important and not infrequent event in meningiomas, predictive immunohistochemical markers have not been identified yet. The aim of this study was to address this clinically relevant problem by systematic retrospective analysis of surgically completely resected meningiomas with and without recurrence, including tumour samples from patients who underwent repeat surgeries. Three established immunohistochemical markers of routine pathological meningioma work-up have been assessed: the proliferative marker Ki-67 (clone Mib1), the tumour suppressor gene p53 and progesterone receptor (PR). All these proteins correlate with the tumour WHO grade, however the predictive value regarding recurrence and progression in tumour grade is unknown. One hundred and fourteen surgical specimens of 70 meningioma patients (16 male and 54 female) in a 16 years' interval have been studied. All tumours had apparently complete surgical removal. On Mib1, PR and p53 immunostained sections, the percentage of labelled tumour cells, the staining intensity and the multiplied values of these parameters (the histoscore) was calculated. Results were statistically correlated with tumour WHO grade, (sub)type, recurrence and progression in WHO grade at subsequent biopsies. Our results confirmed previous findings that the WHO grade is directly proportional to Mib1 and p53 and is inversely proportional to the PR immunostain. We have demonstrated that Mib1 and p53 have a significant correlation with and predictive value of relapse/recurrence irrespective of the histological subtype of the same WHO grade. As a quantitative marker, Mib1 has the best correlation with a percentage of labelled cells, whereas p53 with intensity and histoscore. In conclusion, the immunohistochemical panel of PR, p53, Mib1 in parallel with applying standard diagnostic criteria based on H and E stained sections is sufficient and reliable to predict meningioma recurrence in surgically completely resected tumours.