Probiotics for Inflammatory Bowel Disease; A Deep Dive into Their Impact on Disease Course and Associated Health Risks.

To date, the underlying pathology of inflammatory bowel disease (IBD) is undetermined. Disturbance of intestinal gut microbiota was implicated in many health diseases, including IBD. Increasing evidence suggests that probiotics play a beneficial role in restoring the balance of the gut ecosystem. This review searched multiple databases for relevant works that examined probiotics' possible benefits in adults with IBD. Probiotic mode of action in ulcerative colitis patients and Crohn's disease were examined with respect to probiotic strain, their benefits, and their advantages in adult cases. Eligible studies for inclusion were assessed and analyzed. They were effective in reducing IBD disease course, inducing and maintaining remission, particularly for ulcerative colitis patients, with good efficacy and safety profile. However, the evidence for Crohn's disease was lacking. Probiotics positively affect IBD-related risks, reducing the risk of gastrointestinal malignancy and optimizing treating them. Additionally, they improved reduced fertility odds for both genders. The osteoporosis risk among IBD patients was also reduced, although the duration of use and dose were still not established. There was an encouraging role for them in reducing IBD -cardiovascular risks among cases with acute myocardial infarction and those with chronic heart failure. Finally, they had novel use in reducing IBD-related depression and improved overall mental health. In conclusion, we recommend probiotics as an adjuvant therapeutic option for IBD therapy for ulcerative colitis; however, their role in Crohn's disease needs further research.

Evaluation of immunohistochemical expression of stem cell markers (NANOG and CD133) in normal, hyperplastic, and malignant endometrium.

Cancer stem cells (CSC) are a potential cause for recurrence, metastasis, and resistance of tumors to different therapeutic modalities like hormonal radiotherapy and chemotherapy. We investigated two CSC markers (NANOG and CD 133) in normal, hyperplastic endometrium and endometrial carcinoma. A total of 93 formalin-fixed paraffin-embedded tissue blocks were used for immunohistochemical expression of NANOG and CD133 markers. NANOG expression was detected in 88.37% of endometrial carcinoma cases compared to 15% of the normal proliferative endometrium and 60% of hyperplasia cases. In endometrial carcinoma, high NANOG expression was significantly correlated with high grade, deep myometrial invasion, lymph node metastasis, and high stage with p-values (0.009, 0.005, 0.014, and 0.003, respectively). CD133 was positive in 76.74% of endometrial carcinoma cases, and it showed a significant correlation with deep myometrial invasion, positive lymph node, positive lymphovascular invasion, and high stage (p-values 0.003, 0.001, 0.003, and 0.013, respectively). Normal endometrium showed less expression of CD133 (only 5%) than hyperplasia and endometrial carcinoma with a statistically highly significant difference (p less than 0.0001). Hyperplastic cases with atypia expressed higher CD133 than those without atypia (6 out of 12 versus 3 out of 18). However, this difference was not statistically significant (p-value 0.111). The cancer stem cell markers NANOG and CD 133 are expressed in a high percentage in endometrial carcinoma compared to normal and hyperplasia and their expression is positively correlated with the aggressive behavior of the tumor. High expression of these two markers in apparently normal tissue around the tumor and in hyperplastic conditions with atypia suggests the possibility to use NANOG and CD133 expression as a diagnostic marker distinguishing dysplasia from reactive atypia. Therefore, inhibition of these markers can be a promising method to stop the progression of early cancers.

Diagnostic Value of Cytokeratin 34 beta E12 (Ck34ßE12) and α-Methylacyl-CoA racemase (AMACR) Immunohistochemical Expression in Prostatic Lesions.

BACKGROUND & OBJECTIVE: Some prostatic lesions contain small suspicious foci for prostatic carcinoma in which the morphological features are equivocal. Two immunohistochemical markers namely, cytokeratin 34 beta E12 (Ck34ßE12) and α-Methylacyl-CoA racemase (AMACR), were evaluated in these lesions for a definitive diagnosis and avoiding misdiagnosis or overdiagnosis of prostatic carcinoma. METHODS: A total of 90 paraffin embedded blocks of prostatic tissue were selected and categorized into three groups as follows: 50 cases of benign prostatic hyperplasia (BPH), 20 cases of prostatic carcinoma, and 20 cases of benign prostatic lesions with suspicious foci labeled as ASAP (atypical small acinar proliferation) that occupy not more than 5% of the lesion. These cases were revised for histopathological diagnosis and stained with two immunohistochemical markers: Ck34ßE12 and AMACR. RESULTS: While 92.9% of BPH were positive for Ck34ßE12, 96% of prostatic carcinoma were negative for this marker (P=0.0001). Regarding AMACR, 92.9% of BPH cases were negative, but 92% of prostatic carcinoma cases were positive for this marker (P=0.0001). Out of 20 cases of BPH, 15 cases containing suspicious foci showed Ck34ßE12+/AMACR- (diagnosis: benign), but 5 cases were Ck34ßE12-/AMACR+, for which the diagnosis changed to prostatic carcinoma (P=0.04). CONCLUSION: Immunohistochemical staining with Ck34ßE12 and AMACR improved the diagnostic performance and increased confidence level for establishing definite diagnosis in cases with suspicious foci, in which the morphological features were equivocal. This could help to avoid misdiagnosis or overdiagnosis of prostatic carcinoma that would eventually improve the management of the patient and subsequently the prognosis.

Immunohistochemical expression of interlukin10 (IL10) and heat shock protein-90 (HSP-90) in prostatic carcinoma.

BACKGROUND: Specific cytokines are related to pathologically changed prostate, propose that the balance in cytokine differs in normal and pathological prostate. Of these cytokines the interleukins 10, due to its "pleiotropic" actions in inflammation and angiogenesis, and HSP-90 due to its expression in tumor cells at high levels, suggesting that it has an important role for growth and/or survival of tumor cells. AIMS: Evaluation of HSP-90 and IL10 immunoreactivity in benign prostatic hyperplasia (BPH) and prostatic carcinoma and to correlate this expression with clinicopathological parameters. SETTINGS AND DESIGN: A retrospective study in which 83 Paraffin-embedded tissue specimens including (43) BPH, (40) prostatic carcinoma and (20) normal prostate as control were included between the period of January 2015 and January 2017. PATIENTS, MATERIAL AND METHODS: All the cases were evaluated histopathologically and stained immunohistochemically for IL10 and HSP-90. Only cytoplasmic staining was considered as positive. Immunoreactivity scoring for both markers expression was calculated based on both staining intensity and percentage. STATISTICAL ANALYSIS: Was done using SPSS Version 21 statistical analysis software. P value of <0.05 was considered statistically significant. RESULT: Statistical analysis of HSP-90 and IL10 expression revealed a highly significant correlation of expression of these two markers in advanced Gleason grading and tumor, node, and metastasis (TNM) staging cases of prostatic carcinoma. CONCLUSION: High expression of IL10 and HSP-90 is associated with high grade and stage of prostatic carcinoma. This provides a base for further studies and researches on the role of these investigated proteins as prognostic markers immunotherapy targets for carcinoma of the prostate.

Ki67 expression in invasive breast cancer: the use of tissue microarrays compared with whole tissue sections.

BACKGROUND: Although the prognostic value of Ki67 in breast cancer is well documented, using optimal cut-points for patient stratification, reproducibility of the scoring and interpretation of the results remains a matter of debate particularly when using tissue microarrays (TMAs). This study aims to assess Ki67 expression assessed on TMAs and their matched whole tissue sections (WTS). Moreover, whether the cut-off used for WTS is reproducible on TMA in BC molecular classes and the association between Ki67 expression cut-off, assessed on TMAs and WTS, and clinicopathological parameters and patient outcome were tested. METHOD: A large series (n = 707) of primary invasive breast tumours were immunostained for Ki67 using both TMA and WTS and assessed as percentage staining and correlated with each other, clinicopathological parameters and patient outcome. In addition, MKI67 mRNA expression was correlated with Ki67 protein levels on WTS and TMAs in a subset of cases included in the METABRIC study. RESULTS: There was moderate concordance in Ki67 expression between WTS and TMA when analysed as a continuous variable (Intraclass correlation coefficient = 0.61) and low concordance when dichotomised (kappa value = 0.3). TMA showed low levels of Ki67 with mean percentage of expression of 35 and 22% on WTS and TMA, respectively. MKI67 mRNA expression was significantly correlated with protein expression determined on WTS (Spearman Correlation, r = 0.52) and to a lesser extent on TMA (r = 0.34) (p < 0.001). Regarding prediction of patient outcome, statistically significant differences were detected upon stratification of patients with tumours expressing Ki67 at 10, 15, 20, 25 or 30% in TMA. Using TMA, ≥20% Ki67 provided the best prognostic cut-off particularly in triple-negative and HER2-positive classes. CONCLUSION: Ki67 expression in breast cancer can be evaluated using TMA although different cut-points are required to emulate results from WTS. A cut-off of ≥20% for Ki67 expression in BC provides the best prognostic correlations when TMAs are used.

Prognostic and biological significance of peroxisome proliferator-activated receptor-gamma in luminal breast cancer.

Peroxisome proliferator-activated receptor-gamma (PPARγ) is an adopted orphan receptor that belongs to the nuclear receptor superfamily of transcription factors. PPARγ is regarded as a differentiation factor and it plays an important role in regulating adipogenesis, cell growth, proliferation and tumour progression. In breast cancer (BC), PPARγ agonists were reported to inhibit proliferation and growth invasion and promote phenotypic changes associated with a less malignant and more differentiated status. This study aims to assess the prognostic and biological roles of PPARγ protein expression in a large cohort of BC patients (n = 1100) with emphasis on the luminal oestrogen receptor (ER) positive class. Immunohistochemistry was used to assess the levels of PPARγ expression in BC series prepared as tissue microarrays (TMAs). PPARγ antibody specificity was confirmed using Western blotting. PPARγ nuclear expression was detected in 79 % of the cases and its expression was positively correlated with the hormonal receptors (ER, progesterone receptor and androgen receptor). PPARγ levels were significantly higher in tumours with lobular subtype, smaller size and lower grade, while HER2-positive, ductal or medullary tumours were associated with lower PPARγ levels. Survival analysis showed that PPARγ is associated with better outcome in the whole series as well as in luminal ER-positive class. Cox regression model showed that PPARγ is an independent predictor of outcome. Higher PPARγ was associated with longer survival in patients with ER-positive tumours who did not receive hormone therapy. PPARγ is a good prognostic marker associated with hormone receptors. In patients with luminal BCs, PPARγ is a marker of better prognosis and is associated with longer survival.

Clinical and biological significance of glucocorticoid receptor (GR) expression in breast cancer.

The glucocorticoid receptor (GR) is a member of the nuclear receptor superfamily of transcription factors, which exerts anti-proliferative and anti-apoptotic activities. The GR is expressed in a large proportion of breast cancer (BC) although levels generally decrease during cancer progression. This study aimed to determine the clinical and biological significance of GR expression using a large series of early-stage BC with long-term follow-up and BC cell lines. Immunohistochemistry was used to assess the expression of GR in 999 cases of primary invasive BC prepared as tissue microarrays. Reverse phase protein microarray was used to assess the expression of GR in MCF7 and MDA-MB-231 cell lines. Nuclear expression of GR was observed in 61.6 % of breast tumours and was associated with features of good prognosis including smaller tumour size and lower grade with less pleomorphism and low mitotic count. GR expression was positively correlated with expression of oestrogen (ER) and progesterone receptors. In ER-positive tumours, GR was associated with other features of favourable outcome including FOXA1, GATA3 and BEX1 expression, while low GR expression was associated with high Ki67, p53 and CD71 expression. GR expression is associated with features of good outcome but does not provide prognostic information independent of size, stage and grade. Understanding the receptor and its effects on BC behaviour is essential for avoiding any unwanted effects from the use of glucocorticoids in routine oncology practice.