UNASSIGNED: Choledochal cysts are congenital anomalies that occur as localized cystic or fusiform dilatations of the biliary tree. Reflux and stasis of pancreatic enzymes in the biliary duct may relate to the development of intestinal metaplasia which might be an important factor related to the carcinogenesis of choledochal cyst, thus the expression of beta-catenin in the metaplastic epithelium might be associated with malignant transformation of choledochal cyst epithelium.
UNASSIGNED: This study was conducted at a tertiary care pediatric center between October 2014 and March 2017. Forty patients were evaluated for epithelial lining, mural ulceration, fibrosis, inflammation, and metaplasia.
UNASSIGNED: Out of 40, 12 cases (30.0%) were the infantile age group and 28 cases (70.0%) were in the classic pediatric group. Ulceration was classified as grade 0 (14 cases, 35.0%), grade 1 (17 cases, 42.5%), or grade 2 (nine cases, 22.5%). Inflammation was classified as grade 0 (2 cases, 5.0%), grade 1 (26 cases, 65.0%), or grade 2 (12 cases, 30.0%). Fibrosis was classified as grade 0 (five cases, 12.5%), grade 1 (11 cases, 27.5%), grade 2 (17 cases, 42.5%), or grade 3 (seven cases, 17.5%). Metaplasia was noted in five (12.5%) out of 40 cases. All choledochal cysts with metaplasia showed beta-catenin nuclear positivity on immunohistochemistry and were followed up.
UNASSIGNED: This study emphasizes the importance of detailed histopathological examination and documentation of metaplastic changes. Metaplasia was associated with beta-catenin nuclear positivity. These findings suggest a potential role for beta-catenin as a marker of metaplastic changes in choledochal cysts.

Background and Objectives: Gastric cancer (GC) is one of the most commonly diagnosed cancers and the fourth cause of cancer death worldwide. Personalised treatment improves GC outcomes. A molecular classification is needed to choose the appropriate therapy. A classification that uses on-slide biomarkers and formalin-fixed and paraffin-embedded (FFPE) tissue is preferable to comprehensive genomic analysis. In 2016, Setia and colleagues proposed an on-slide classification; however, this is not in widespread use. We propose a modification of this classification that has six subgroups: GC associated with Epstein-Barr virus (GC EBV+), GC with mismatch-repair deficiency (GC dMMR), GC with epithelial-mesenchymal transformation (GC EMT), GC with chromosomal instability (GC CIN), CG that is genomically stable (GC GS) and GC not otherwise specified (GC NOS). This classification also has a provision for biomarkers for current or emerging targeted therapies (Her2, PD-L1 and Claudin18.2). Here, we assess the implementation and feasibility of this inclusive working classification. Materials and Methods: We constructed a tissue microarray library from a cohort of 79 resection cases from FFPE tissue archives. We used a restricted panel of on-slide markers (EBER, MMR, E-cadherin, beta-catenin and p53), defined their interpretation algorithms and assigned each case to a specific molecular subtype. Results: GC EBV(+) cases were 6%, GC dMMR cases were 20%, GC EMT cases were 14%, GC CIN cases were 23%, GC GS cases were 29%, and GC NOS cases were 8%. Conclusions: This working classification uses markers that are widely available in histopathology and are easy to interpret. A diagnostic subgroup is obtained for 92% of the cases. The proportion of cases in each subgroup is in keeping with other published series. Widescale implementation appears feasible. A study using endoscopic biopsies is warranted.

BACKGROUND: A myriad of therapeutic modalities for alopecia areata are available; however, none is of high level of evidence, creating an immense need for the evaluation of other treatment modalities, of which topical sodium valproate is of potential role via proposed decrease in beta-catenin breakdown, despite its well-known side effect of hair fall as an oral therapy.
OBJECTIVE: Evaluating the efficacy and the safety of sodium valproate (SV)-loaded nanospanlastics, in comparison to topical corticosteroids, this is the currently available gold standard topical treatment for patchy AA.
METHODS: A total of 66 patients with patchy AA were randomly assigned to receive either topical mometasone furoate lotion or topical SV applied twice daily to all patches except a control patch, which was left untreated. Clinical, trichoscopic and biochemical assessments of beta-catenin tissue levels and Axin-2 gene expression were carried out at baseline and after 3 months.
RESULTS: Both therapeutic modalities were comparable. Potential efficacy was highlighted by significant improvement in the representative patch, the largest treated patch, to the control patch, the smallest untreated patch in both steroid and valproate groups (p = 0.027, 0.003 respectively). Both beta-catenin levels and Axin-2 gene expression were reduced after treatment, pointing to the inhibitory effect of dominating uncontrolled inflammatory milieu. Baseline beta-catenin was found to significantly negatively correlate with improvement in the representative patch in patients with baseline level above 0.42 ng/ml (p = - 0.042).
CONCLUSIONS: Both topical SV and steroids are of comparable modest efficacy. Thus, further evaluation of SV is due in combination with intralesional steroids and other anti-inflammatory treatment modalities, together with developing individualized approaches based on baseline beta-catenin level.
RESULTS:
UNASSIGNED: NCT05017454, https://clinicaltrials.gov/ct2/show/NCT05017454 .

Ampullary carcinomas are uncommon malignant tumours of the digestive system, they usually are adenocarcinomas presenting histologically as three types: intestinal, pancreaticobiliary and mixed. β-catenin is a multifunctional protein involved in physiological homoeostasis and intracellular adhesion. Abnormal nuclear accumulation of β-catenin has been described in many malignancies such as colon, breast, liver and others. The relationships between the immunohistochemical expression of β-catenin and the subtype, the grade and the stage of ampullary carcinoma are studied.
UNASSIGNED: A cross-sectional retrospective study was done on 25 formalin-fixed paraffin-embedded blocks of ampullary carcinoma: Cases were collected from the archives of the pathology department in the Gastroenterology and hepatology teaching hospital, medical city/ Baghdad from January 2019 to March 2022. The data of the patients and the characteristics of the tumour were derived from the pathological reports; additional sections from the block were stained with β-catenin immunohistochemically.
UNASSIGNED: 25 paraffin blocks from patients with ampullary carcinoma (12 males, 13 females) were included in the study. 64% of the cases are classified as pancreaticobiliary, 20% as mixed, 12% as intestinal and 4% as adenosquamous type. Eighty-four percent of the cases are moderately differentiated, and the remaining is poorly differentiated. Most cases show strong β-catenin membranous staining and 80% express 3+ staining of cytoplasmic β-catenin. Regarding nuclear β-catenin staining, 56% has negative staining.
UNASSIGNED: No significant association was found between the cytoplasmic and the nuclear expression of β-catenin and the tumour type, size and lymph node status. The grade of the tumour showed a significant correlation with the cytoplasmic expression; while, no correlation was noted with the nuclear expression. This study results do not support the use of beta-catenin as a diagnostic marker or prognostic marker in ampullary cancers.

Sebaceous carcinoma (SC) is a rare malignant neoplasm with sebaceous differentiation. SC is classified into eyelid and extraocular SC clinically. Most studies have focused on the eyelid SC in terms of pathogenesis, treatment, and prognosis. In skin, Wnt/beta-catenin and hedgehog signaling are two major pathways in sebaceous differentiation. We aimed to characterize the clinical and histopathological features of extraocular SC and to measure the expression of beta-catenin, lymphoid enhancer-binding factor 1 (LEF1), sonic hedgehog (Shh), and protein patched homolog 1 (PTCH) in extraocular SC. Ten cases of extraocular SC were identified from 2007 to 2020. The clinical features, microscopic findings, and prognosis were analyzed. Immunohistochemical stain for beta-catenin, LEF1, Shh, and PTCH were performed in extraocular SC and other benign sebaceous tumors including sebaceous hyperplasia, sebaceous adenoma, and sebaceoma. The male:female ratio was 4:6. The median onset age was 73.5 years (range, 43-88). Seven patients out of 10 were diagnosed after 60 years. Most extraocular SC were located on the head and neck with indurated plaque. Two patients had concurrent internal cancers and three patients showed lymph node metastasis at time of presentation. Five-year overall-survival was 40%. Beta-catenin was expressed membranously in all sebaceous hyperplasia, but was expressed variably in extraocular SC (1/5). While LEF1 was unequivocally expressed in normal hair follicles, LEF1 expression was absent in all extraocular SC and benign sebaceous tumors. Regarding the sonic hedgehog signaling, Shh and PTCH were all expressed in the cytoplasm of sebaceous hyperplasia, sebaceous adenoma, and sebaceoma. In contrast, PTCH was absent in all cases of extraocular SC and only 50% of the extraocular SC expressed cytoplasmic Shh. To conclude, extraocular SC commonly affects facial skin in the elderly. Inactivated Wnt/beta-catenin and aberrant hedgehog pathway may contribute to the carcinogenesis of extraocular SC. Further studies may be required to elucidate the causative mechanism of these pathways in extraocular SC.

UNASSIGNED: Oral potentially malignant disorders have increased propensity to turn malignant than its apparently normal counterparts. Histopathological examination, although gold standard, needs adjunct technique to give accurate diagnosis. Immunohistochemistry has proved to be a promising adjunct to aid in the diagnosis so far. The quest for a definitive marker is still on. Beta-catenin (β-catenin), a structural protein has been evaluated to identify its likely role in malignant transformation of potentially malignant lesions and possibly designate it as one of the identifiable signature molecules in the transformation.
UNASSIGNED: To evaluate and estimate the expression of β-catenin in different grades of dysplasia, oral submucous fibrosis (OSMF) and normal mucosa and compare the same.
UNASSIGNED: A total number of 40 cases including different grades of dysplasia, OSMF and normal mucosa were immunohistochemically stained, location and intensity of its expression were evaluated for β-catenin. The results were statistically analyzed using the one-way analysis of variance and Chi-square test.
UNASSIGNED: The expression of β-Catenin in the cytoplasm as well as in the nucleus increased from mild-to-moderate dysplasia to OSMF and to severe epithelial dysplasia in an increasing order. The expression is seen to translocate from membranous to cytoplasm to nucleus indicating a proliferative potential in these group of lesions.
UNASSIGNED: β-catenin is a promising marker which indicates the malignant transformation potential in the higher grades of dysplasia and OSMF.

OBJECTIVE: NFKBIA is frequently encountered. However, its expression and relevance of the proliferation, invasion, and migration in human cervical cancer (CC) remain unclear. The role and novel mechanism of NFKBIA in CC progression were investigated in this study.
METHODS: We analyzed the expression of NFKBIA in CC and adjacent normal tissues and explored the proliferation, migration, and invasion of HeLa cells by treating with either wild-type NFKBIA plasmid or NFKBIA siRNA. Effect of NFKBIA on the epithelial-mesenchymal transition (EMT) and the β-catenin-mediated transcription of target genes were evaluated subsequently.
RESULTS: NFKBIA expression was lower in CC tissues than that of adjacent tissues. An obvious dysregulation of NFKBIA overexpression was revealed in CC cell proliferation, invasion, and migration, which differed from the effect of knockdown NFKBIA. NFKBIA overexpression facilitated the expression of both phosphorylated β-catenin and E-cadherin protein. It inhibited the expression of vimentin, TWIST, as well as downstream targets of β-catenin including c-MYC, TCF-4 and MMP14. Conversely, NFKBIA silencing elevated the expression of c-MYC, TCF-4, and MMP14, and promoted the EMT in HeLa cells. Both endogenous and exogenous NFKBIA interacted with β-catenin. Moreover, β-catenin overexpression stemmed effects of NFKBIA on the proliferation, migration, and invasion of HeLa cells. By overexpressing NFKBIA in vivo, the volume and size of tumors were notably decreased, while no obvious alteration was found in mice body weight.
CONCLUSIONS: By inhibiting β-catenin-mediated transcription, NFKBIA functioning as a tumor suppressor might be introduced as a novel anti-metastatic agent for the treatment of targeted CC.

An increasing number of \'-omics\' datasets, generated by labs all across the world, are becoming available. They contain a wealth of data that are largely unexplored. Not every scientist, however, will have access to the required resources and expertise to analyze such data from scratch. Fortunately, a growing number of investigators is dedicating their time and effort to the development of user friendly, online applications that allow researchers to use and investigate these datasets. Here, we will illustrate the usefulness of such an approach. Using regulation of Wnt7b expression as an example, we will highlight a selection of accessible tools and resources that are available to researchers in the area of mammary gland biology. We show how they can be used for in silico analyses of gene regulatory mechanisms, resulting in new hypotheses and providing leads for experimental follow up. We also call out to the mammary gland community to join forces in a coordinated effort to generate and share additional tissue-specific \'-omics\' datasets and thereby expand the in silico toolbox.

Beta-catenin, encoded by the CTNNB1 gene, plays an important role in cell proliferation. Mutations of CTNNB1 are oncogenic in several tumor types and are often associated with a nuclear abnormal expression. However, such mutations have only rarely been reported in non-small cell lung carcinomas and their clinical signification is not well described. Our study was conducted on 26 CTNNB1-mutated non-small cell lung carcinomas. Tumors were routinely tested by next generation sequencing for mutations in exon 3 of CTNNB1 gene. Twenty three cases were from a series of 925 tumors (2.48%). The hospital files and pathological data, from surgical samples (n = 16), small biopsies (n = 5) and trans-bronchial fine needle aspirations (n = 5), were reviewed. Immunohistochemistry was performed with an anti-beta-catenin antibody. There were 10 female and 16 male patients aged 52 to 83. Eleven of 25 patients were no-smoking or light smokers. Three cases were diagnosed while under treatment with EGFR tyrosine kinase inhibitor. There were 25 adenocarcinomas and 1 squamous cell carcinoma. Most adenocarcinomas had a papillary component and were TTF1-positive. One case was a well-differentiated fetal adenocarcinoma. Eleven cases (42%) with CTNNB1 mutations showed associated EGFR mutations. The frequency of CTNNB1 mutations was higher among EGFR mutated carcinomas. Immunohistochemistry showed heterogeneous nuclear or cytoplasmic abnormal expression. Our study shows that CTNNB1 mutations mostly occur in TTF1-positive adenocarcinomas with a papillary pattern. These mutations are often associated with EGFR mutations and possibly interfer in the mechanism of resistance to tyrosine kinase inhibitors. Our experience suggests that immuno-histochemistry cannot be used for screening.

OBJECTIVE: To examine the immunohistochemical expression of Ki-67 and beta-catenin in pseudoepitheliomatous hyperplasia and squamous cell carcinoma (SCC) in oral mucosal biopsies.
METHODS: In this comparative cross sectional study, 70 cases of each PEH and OSCC were taken from the patients of both genders and in all age groups. Study was conducted at Armed Forces Institute of Pathology (AFIP), Rawalpindi from Dec 2017 to March 2019. Statistical analysis was done with the help of SPSS Version 24.0. We used Chi-Squared test with p value of < 0.05 which was considered as statistically significant.
RESULTS: In the current study, 80 (57.1%) male and 60 (42.8%) female patients with the mean age of 51.69 ± 16.121 (mean ± SD) years were included. It was found that 6-25% Ki-67 labeling index was observed in all (70) PEH cases, which involved only basal layer of the epithelium. Whereas, Ki-67 labeling index was highly expressed in tumor of high grade malignancy than tumor of low grade malignancy. On the other hand, expression of membranous beta-catenin was higher in PEH and cytoplasmic beta-catenin expression was higher in OSCC.
CONCLUSIONS: It is concluded that Ki-67 and beta-catenin showed significant expression in PEH and OSCC in oral mucosal biopsies especially those with intense inflammation or unoriented tissue, helping the clinicians to arrive at a final diagnosis before planning any surgical intervention.