Immunohistochemical Profile of Tumor Pathways and Prognostic Significance in Colon Adenocarcinomas.

The current study examined the immunohistochemical expression levels of molecules on carcinogenesis pathway and evaluated their clinicopathologic significance in colorectal adenocarcinoma (CRA). A total of 189 CRA and 20 colonic mucosal tissue samples were evaluated by immunohistochemical staining using 38 antibodies targeting the known molecules that play roles in developmental pathways of various tumors. The immunoexpression data of the patients were compared to clinicopathologic parameters. Expression loss of MLH1, MSH2, MSH6, PMS2, PTEN, Smad4 and E-cadherin, and overexpression of ALDH1, CD44, CAIX, P504S (AMACR), TGFΒ, and ZEB1 were statistically significant in CRA compared to normal colon mucosa. Long-term clinical follow-up findings in our cases suggested that AMACR, CAIX, ALDH1, TGFΒ, ZEB1 overexpression, and cyclinD1, p53, E-cadherin, and PTEN inactivity might be useful markers of a poor prognosis in CRA. In survival analyses, the expression of CAIX and AMACR were significantly associated with overall survival in both the univariate and multivariate analyses (log-rank test; p < 0.01 and p < 0.05, respectively).

Gastric Adenocarcinoma Biomarker Expression Profiles and their Prognostic Value.

Expression levels of several molecules implicated in carcinogenesis were examined by immunohistochemical staining, and the prognostic significance of their expression levels in gastric adenocarcinoma (GA) was evaluated. A total of 115 GA and 20 control gastric tissue samples were evaluated by immunohistochemistry using 33 antibodies targeting molecules known to play a part in the development of various tumors. Overexpression of carbonic anhydrase IX (CAIX) and loss of AT-rich interactive domain-containing protein 1A (ARID1A), aldehyde dehydrogenase 1 (ALDH1), and CD44 expression in GA patients were significantly correlated with lymph node (LN) metastasis, advanced tumor stage, and poor prognosis. The results demonstrated that ALDH1A and ARID1A may be strong independent prognostic factors associated with overall survival and recurrence-free survival (p < 0.01 and p < 0.05, respectively). Our results demonstrated that ALDH1, CD44, ARID1A, and CAIX in immunoreactive GA tumor cells exhibit different expression profiles compared with control cells and that these differences are associated with patient survival. The molecules with differential expression profiles were associated with some common functions, including hypoxia, epithelial-to-mesenchymal transition, and SW1/SNF-mediated chromatin remodeling. In addition, the loss of ALDH1, ARID1A, and CD44 and the overexpression of CAIX are important for tumor invasion and metastasis; therefore, they may serve as useful prognostic indicators of long-term survival in patients with GA. In conclusion, our study found that abnormal expression of some of the proteins evaluated in GA tumor cells might have an important role in carcinogenesis and tumor progression and thus may influence the prognosis of patients with GA.

Stromal Clues in Endometrial Carcinoma: Loss of Expression of ß-Catenin, Epithelial-Mesenchymal Transition Regulators, and Estrogen-Progesterone Receptor.

Epithelial-stroma interactions in the endometrium are known to be responsible for physiological functions and emergence of several pathologic lesions. Periglandular stromal cells act on endometrial cells in a paracrine manner through sex hormones. In this study, we immunohistochemically evaluated the expression of epithelial-mesenchymal transition regulators (SNAIL/SLUG, TWIST, ZEB1), adhesion molecules (ß-catenin and E-cadhenin), estrogen (ER)-progesterone (PR) receptor and their correlation with each other in 30 benign, 148 hyperplastic (EH), and 101 endometrioid-type endometrial carcinoma (EC) endometria. In the epithelial component, loss of expression in E-cadherin, ER and PR, and overexpression of TWIST and ZEB1 were significantly higher in EC than in EH (P<0.01). In the periglandular stromal component, ß-catenin and SNAIL/SLUG expression were significantly higher in normal endometrium and simple without atypical EH compared with complex atypical EH and EC (P<0.01). In addition, periglandular stromal TWIST expression was significantly higher in EH group compared with EC (P<0.05). There was significantly negative correlation between ß-catenin and ER, TWIST and ER, and TWIST and PR in hyperplastic and carcinomatous glandular epithelium, whereas there was a significantly positive correlation between ß-catenin and SNAIL-SLUG, ß-catenin and TWIST, ß-catenin and ER, ß-catenin and PR, SNAIL-SLUG and ER, SNAIL-SLUG and PR, TWIST and ER, TWIST and PR, in periglandular/cancer-associated stromal cells (P<0.01). In conclusion, the pattern of positive and negative correlations in the expression of epithelial-mesenchymal transition regulators (SNAIL-SLUG and TWIST), sex hormone receptors (ER and PR), and ß-catenin between ECs and hyperplasia, as well as between epithelium and stroma herein, is suggestive of a significant role for these proteins and their underlying molecular processes in the development of endometrial carcinomas.

Folate receptor α expression and significance in endometrioid endometrium carcinoma and endometrial hyperplasia.

Endometrioid-type endometrial carcinoma (EEC) developing on the ground of endometrial hyperplasia (EH) is amongst the most commonly observed type of cancer in the world. Folate receptor α (FRα) is a vitamin molecule that has a role in cell proliferation. The fact that FRα, which is known to be needed extremely by the cells of malignancies that proliferate rapidly, is present in limited amounts in normal tissues while it is overexpressed in malignant cells of the same tissues makes folate a candidate for target molecular therapy. In our study, FRα expression in 214 cases, with 95 diagnosed within EEC and 119 with EH, was studied immunohistochemically. FRα expression in EEC was found significantly high compared to EH and normal endometrium (P<0.01). Similarly, FRα expression in EH cases with complex atypia were significantly high compared to other hyperplasia subgroups (P<0.01). The findings of our results make us think that FRα overexpression may play a role in the EEC carcinogenesis and carcinoma progression from EH. Furthermore, we suggest that it can be helpful in the treatment of EEC and/or transition from hyperplasia stage to EEC as a molecular therapy targeting receptors labeled with antibody-based props containing FRα. Finally, we suggest that FRα may be used, based on the expression intensity, as a supplemental option to determine the patients that shall be directed to radical therapy amongst patients with complex atypical EH.

Relation of stem cell markers ALDH1 and CD44 with clinicopathological factors in urothelial carcinomas of urinary bladder.

Molecular studies are ongoing in regards to superficial urothelial carcinoma of the bladder (UCB) either to define targeted therapy or to better select aggressive therapy candidates and also to delineate the outcome of the disease. In this study, we aimed to present the impact of ALDH1 and CD44 as stem cell markers in tumorigenesis and their prognostic value in urothelial carcinoma. We investigated ALDH1 and CD44 immunohistochemically in paraffin-embedded material of 125 non-muscle-invasive (NMI) cases in 163 UCB patients. In the NMI-UCB subgroup, we found ALDH1 to be significantly correlated with all poor prognostic factors, including high stage (≥pT2), high grade, recurrence and progression development and poor survey (P=0.001) in contrast to CD44 expression (P>0.05). Although ALDH1 expression had a good correlation with a poor clinical course of UCB, it could be used as a molecular marker to determine the best treatment strategy and could contribute to the development of targeted therapies.

Evaluation of histopathological changes in control biopsies which taken 48 sessions after NBUVB phototherapy for early-stage mycosis fungoides.

BACKGROUND: There are not many studies investigating histomorphological changes in 48 sessions in patients with early-stage MF after narrowband UVB (NBUVB) treatment. Our purpose is to evaluate histological features of phototherapy after 48 sessions and determine which parameters are more reliable for controlling skin biopsies. METHODS: Biopsies of 32 patients with early stage of MF, who were treated with NBUVB phototherapy, were histologically evaluated before and after the treatments, including epidermotropism, stratum corneum, epidermal thickness, dermal infiltration, papillary dermal fibrosis, vascular alterations, and other dermal changes. We discuss the histomorphological effects of NBUVB phototherapy on skin biopsies by comparing the responders with nonresponders, with before and after the treatment. RESULTS: 9 patients (28%) did not give any response to treatment. Alleviation in epidermotropism, increases in parakeratosis and normal keratosis, perivascular infiltration, and melanophages, decrease in the lichenoid/patchy lichenoid infiltration pattern after the treatment was statistically significant. Comparing by response, normalization of stratum corneum and epidermis, orthohyperkeratosis, decrease in linearly arranged cells, the lichenoid/patchy lichenoid infiltration, the loss of inflammation were statistically significant in responders group. CONCLUSION: We detected a significant decrease in linearly arranged cells after phototherapy, indicating that it is an "important diagnostic parameter" in evaluation of therapeutic response.