Search Results (5)

Atypical polypoid adenomyoma (APA) is a benign uterine lesion with a premalignant potential and occurs in women of reproductive age. The histological pattern is characterized by irregular epithelial proliferation and muscular stroma. Based on a case report, we performed a systematic review of the literature to assess the main immunohistochemical and molecular markers that contribute to its differential diagnosis against endometrial adenocarcinoma (EC). The distinction is essential for offering to patients a conservative treatment compared to the radical management required for endometrial cancer, a critical issue for the significant physical and psychological consequences that one procedure or another can have on women’s health. We performed a meta-analysis of the immunohistochemical markers used for the histological diagnosis of APA, comparing it with our case study. The evaluated markers were beta-catenin, h-caldesmon, desmin, vimentin, smooth muscle alpha-actin, CD10, Ki67, estrogen receptor (ER), progesterone receptor (PR), pan-cytokeratin, PTEN, PMS2, MSH2, MSH6, p53, MLH1, and p16. Discrepancies were observed in the expression of CD10, h- caldesmon, and p16 when comparing APA with EC. The results of the case evaluated by our team showed beta-catenin nuclear expression and positive immunostaining for pan-cytokeratin, ER, and PR in the glands; smooth muscle actin and desmin positive expression in stromal muscle; and p16 positive immunostaining in squamous morules. Moreover, the c.94G>T p. (Asp132Tyr) mutation in the CTNNB1 gene was detected. This study supports the combination of appropriate immunohistochemical and molecular markers, along with the presumptive histological diagnosis, and determines the correct classification of the lesion as APA and not as other malignant pathologies, allowing for the establishment of a treatment protocol adjusted to the biological reality of this pathology. Full article

Background: Desmoid-type fibromatosis (DTF) is a locally aggressive myofibroblastic/fibroblastic neoplasm with a high risk of local recurrence. It has a variety of histologic features that might confuse diagnosis, especially when detected during core needle biopsy. The Wnt/β-catenin pathway is strongly linked to the pathogenesis of DT fibromatosis. Method: This study examined 33 desmoid-type fibromatoses (DTFs) from 32 patients, analyzing its clinical characteristics, histologic patterns, occurrence rates, relationship with clinical outcomes, immunohistochemical and molecular findings. Results: The DTFs exhibit a range of 1 to 7 histologic patterns per tumor, including conventional, hypercellular, myxoid, hyalinized/hypocellular, staghorn/hemangiopericytomatous blood vessels pattern, nodular fasciitis-like, and keloid-like morphology. No substantial association was found between the existence of different histologic patterns and the clinical outcome. All thirty-three (100%) samples of DTF had a variable percentage of cells that were nuclear positive for β-catenin. An NGS analysis detected novel non-CTNNB1 mutations in two DTFs, including BCL10, MPL, and RBM10 gene mutations. Conclusions: This study reveals a diverse morphology of DTFs that could result in misdiagnosis. Therefore, surgical pathologists must comprehend this thoroughly. Also, the importance of the newly identified non-CTNNB1 gene mutations is still unclear. More research and analyses are needed to completely grasp the clinical implications of these mutations. Full article

Male Tsumura-Suzuki Obese Diabetes (TSOD) mice, a spontaneous metabolic syndrome model, develop non-alcoholic steatohepatitis and liver tumors by feeding on a standard mouse diet. Nearly 70% of liver tumors express glutamine synthetase (GS), a marker of hepatocellular carcinoma. In contrast, approximately 30% are GS-negative without prominent nuclear or structural atypia. In this study, we examined the characteristics of the GS-negative tumors of TSOD mice. Twenty male TSOD mice were sacrificed at 40 weeks and a total of 21 tumors were analyzed by HE staining and immunostaining of GS, liver fatty acid-binding protein (L-FABP), serum amyloid A (SAA), and beta-catenin. With immunostaining for GS, six (29%) tumors were negative. Based on the histological and immunohistological characteristics, six GS-negative tumors were classified into several subtypes of human hepatocellular adenoma (HCA). One large tumor showed generally similar findings to inflammatory HCA, but contained small atypical foci with GS staining and partial nuclear beta-catenin expression suggesting malignant transformation. GS-negative tumors of TSOD mice contained features similar to various subtypes of HCA. Different HCA subtypes occurring in the same liver have been reported in humans; however, the diversity of patient backgrounds limits the ability to conduct a detailed, multifaceted analysis. TSOD mice may share similar mechanisms of HCA development as in humans. It is timely to review the pathogenesis of HCA from both genetic and environmental perspectives, and it is expected that TSOD mice will make further contributions in this regard. Full article

Fagraea berteroana is a tree used in traditional medicine in various islands of the South Pacific. Here, we studied its hair growth-inducing properties as suggested by one of its Marquesan ethno-uses in haircare. The ethyl acetate extract of the fruits of F. berteroana (FEAE) and four resulting fractions (FEAE-F0, FEAE-F1, FEAE-F2, and FEAE-F3) were tested on hair follicle dermal papilla cells to determine their cell proliferative activity. Furthermore, RT-qPCR analysis enabled gene modulation analysis, while immunostaining of the β-catenin protein was used to follow protein regulation. We found that the plant extracts induced a controlled, dose-dependent cell proliferation. FEAE-F0 simultaneously down-regulated Bone Morphogenetic Protein 2 (BMP2) mRNA expression and upregulated Cyclin-D1 (CCND1) gene expression, which suggests an involvement in the regulation of the Wnt and Transforming Growth Factor beta (TGFβ) pathways that control the hair cycle. FEAE-F0 exhibited a 1.34-fold increase of nuclear β-catenin protein. This is indicative of an active hair growth state. Thus, we conclude that FEAE-F0 could be an innovative candidate in hair care, which opens interesting leads to promote the Marquesan cosmetopoeia. Full article

The susceptibility of brain to secondary formation from lung cancer primaries is a well-known phenomenon. In contrast, the molecular basis for invasion and metastasis to the brain is largely unknown. In the present study, 31 brain metastases that originated from primary lung carcinomas were analyzed regarding over expression of Dishevelled-1 (DVL1), Dishevelled-3 (DVL3), E-cadherin (CDH1) and beta-catenin (CTNNB1). Protein expressions and localizations were analyzed by immunohistochemistry. Genetic alterations of E-cadherin were tested by polymerase chain reaction (PCR)/loss of heterozygosity (LOH). Heteroduplex was used to investigate mutations in beta-catenin. DVL1 and DVL3 showed over expression in brain metastasis in 87.1% and 90.3% of samples respectively. Nuclear staining was observed in 54.8% of cases for DVL1 and 53.3% for DVL3. The main effector of the Wnt signaling, beta-catenin, was up-regulated in 56%, and transferred to the nucleus in 36% of metastases. When DVL1 and DVL3 were up-regulated the number of cases with nuclear beta-catenin significantly increased (p = 0.0001). Down-regulation of E-cadherin was observed in 80% of samples. Genetic analysis showed 36% of samples with LOH of the CDH1. In comparison to other lung cancer pathologies, the diagnoses adenocarcinoma and small cell lung cancer (SCLC) were significantly associated to CDH1 LOH (p = 0.001). Microsatellite instability was detected in one metastasis from adenocarcinoma. Exon 3 of beta-catenin was not targeted. Altered expression of Dishevelled-1, Dishevelled-3, E-cadherin and beta-catenin were present in brain metastases which indicates that Wnt signaling is important and may contribute to better understanding of genetic profile conditioning lung cancer metastasis to the brain. Full article