Ovarian cancer is a leading cause of death among women with gynecological cancers, and is often diagnosed at advanced stages, leading to poor outcomes. This review explores genetic aspects of high-grade serous, endometrioid, and clear-cell ovarian carcinomas, emphasizing personalized treatment approaches. Specific mutations such as TP53 in high-grade serous and BRAF/KRAS in low-grade serous carcinomas highlight the need for tailored therapies. Varying mutation prevalence across subtypes, including BRCA1/2, PTEN, PIK3CA, CTNNB1, and c-myc amplification, offers potential therapeutic targets. This review underscores TP53\'s pivotal role and advocates p53 immunohistochemical staining for mutational analysis. BRCA1/2 mutations\' significance as genetic risk factors and their relevance in PARP inhibitor therapy are discussed, emphasizing the importance of genetic testing. This review also addresses the paradoxical better prognosis linked to KRAS and BRAF mutations in ovarian cancer. ARID1A, PIK3CA, and PTEN alterations in platinum resistance contribute to the genetic landscape. Therapeutic strategies, like restoring WT p53 function and exploring PI3K/AKT/mTOR inhibitors, are considered. The evolving understanding of genetic factors in ovarian carcinomas supports tailored therapeutic approaches based on individual tumor genetic profiles. Ongoing research shows promise for advancing personalized treatments and refining genetic testing in neoplastic diseases, including ovarian cancer. Clinical genetic screening tests can identify women at increased risk, guiding predictive cancer risk-reducing surgery.

Hepatocellular carcinoma (HCC) is a liver cancer, highly heterogeneous both at the histopathological and molecular levels. It arises from hepatocytes as the result of the accumulation of numerous genomic alterations in various signaling pathways, including canonical WNT/β-catenin, AKT/mTOR, MAPK pathways as well as signaling associated with telomere maintenance, p53/cell cycle regulation, epigenetic modifiers, and oxidative stress. The role of WNT/β-catenin signaling in liver homeostasis and regeneration is well established, whereas in development and progression of HCC is extensively studied. Herein, we review recent advances in our understanding of how WNT/β-catenin signaling facilitates the HCC development, acquisition of stemness features, metastasis, and resistance to treatment. We outline genetic and epigenetic alterations that lead to activated WNT/β-catenin signaling in HCC. We discuss the pivotal roles of CTNNB1 mutations, aberrantly expressed non-coding RNAs and complexity of crosstalk between WNT/β-catenin signaling and other signaling pathways as challenging or advantageous aspects of therapy development and molecular stratification of HCC patients for treatment.

BACKGROUND: A recent systematic review published in Head and Neck Pathology found that 3.8% of dentinogenic ghost cell tumors harbor duct-like/ cribriform architecture. Herein we discuss this finding regarding the differential diagnosis of this tumor with adenoid ameloblastoma.
METHODS: A critical review of some microscopic findings reported in a recent paper published in the Head and Neck Pathology Journal was done.
RESULTS: Although there are overlapping microscopic features with dentinogenic ghost cell tumor, adenoid ameloblastoma is distinguished by the combination of duct-like structures and whorls/morules. In our opinion, at least some cases previously diagnosed as dentinogenic ghost cell tumors may now be more accurately classified as adenoid ameloblastoma.
CONCLUSIONS: We conclude that a reassessment of dentinogenic ghost cell tumor cases using the diagnostic criteria proposed by the new WHO classification of Head and Neck Tumors (2022) is warranted.

Aim: Desmoid tumor (DT) is a rare, locally aggressive benign neoplasm with a high recurrence rate. The majority of sporadic DTs are associated with mutations in CTNNB1, but whether CTNNB1 mutations are associated with the risk of DT recurrence remains unclear. The goal of this meta-analysis was to evaluate the association between CTNNB1 mutation and recurrence in surgically treated DT patients. Methods: PubMed, Embase and Cochrane library were systematically searched. The outcome of interest was the risk of recurrence. The number of patients with CTNNB1 mutation and the number of recurrences they developed were recorded and compared. The quality of these studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Odds ratios and variances were calculated and pooled. Results: A total of eight studies were identified including 637 patients. S45F-mutated DTs were more likely to recur compared with wild type, T41A and other mutated DTs. However, there were no statistically significant differences in the rate of recurrence between wild type and T41A mutation or other mutation. Conclusions: Among CTNNB1 mutations, the mutation S45F is a high-risk factor for recurrence of DT and may be a predictive marker for the recurrence of sporadic DT.

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.

Papillary thyroid carcinoma with nodular fasciitis-like stroma (PTC-NFS) is a rare lesion with dual pathological features, that behaves more aggressively if positive for β-catenin gene (CTNNB1) mutations. Recently, we encountered a recurrent PTC-NFS with CTNNB1 mutations. A 48-year-old female presented with a recurrent enlarging tumor with a diagnosis of desmoid-type fibromatosis 6 months after her initial operation for PTC-NFS. Over a 2-year observation period, she underwent remedial surgery to resect the recurrent tumor. During the operation, the left recurrent laryngeal nerve was engulfed and scarified. Local invasion, β-catenin aberrant staining, and CTNNB1 mutations were detected both in the primary tumor stroma and the recurrent tumor. This case indicates that CTNNB1 mutation screening and β-catenin staining should be performed in PTC-NFS cases as a predictor for recurrence. If either of these are positive, a wider surgical resection should be adopted to achieve negative margins. Otherwise, radiotherapy should be considered. Furthermore, the lesion might be better known as papillary thyroid carcinoma with desmoid-type fibromatosis in such situations to reflect its local aggressive nature.

Ductal adenocarcinoma of the prostate is an aggressive subtype, with high rates of biochemical recurrence and overall poor prognosis. It is frequently found coincident with conventional acinar adenocarcinoma. The genomic features driving evolution to its ductal histology and the biology associated with its poor prognosis remain unknown.
To characterize genomic features distinguishing ductal adenocarcinoma from coincident acinar adenocarcinoma foci from the same patient.
Ten patients with coincident acinar and ductal prostate cancer underwent prostatectomy. Laser microdissection was used to separately isolate acinar and ductal foci. DNA and RNA were extracted, and used for integrative genomic and transcriptomic analyses.
Single nucleotide mutations, small indels, copy number estimates, and expression profiles were identified. Phylogenetic relationships between coincident foci were determined, and characteristics distinguishing ductal from acinar foci were identified.
Exome sequencing, copy number estimates, and fusion genes demonstrated coincident ductal and acinar adenocarcinoma diverged from a common progenitor, yet they harbored distinct alterations unique to each focus. AR expression and activity were similar in both histologies. Nine of 10 cases had mutually exclusive CTNNB1 hotspot mutations or phosphatase and tensin homolog (PTEN) alterations in the ductal component, and these were absent in the acinar foci. These alterations were associated with changes in expression in WNT- and PI3K-pathway genes.
Coincident ductal and acinar histologies typically are clonally related and thus arise from the same cell of origin. Ductal foci are enriched for cases with either a CTNNB1 hotspot mutation or a PTEN alteration, and are associated with WNT- or PI3K-pathway activation. These alterations are mutually exclusive and may represent distinct subtypes.
The aggressive subtype ductal adenocarcinoma is closely related to conventional acinar prostate cancer. Ductal foci contain additional alterations, however, leading to frequent activation of two targetable pathways.

Desmoid tumors (DT) are rare, benign, fibroblastic neoplasm with challenging histological diagnosis. DTs can occur sporadically or associated with the familial adenomatous polyposis coli (FAP). Most sporadic DTs are associated with β-catenin gene (CTNNB1) mutations, while mutated APC gene causes FAP disease. microRNAs (miRNAs) are involved in many human carcinogenesis.The miRNA profile was analyzed by microarray in formalin-fixed, paraffin-embedded (FFPE) specimens of 12 patients (8 sporadic, 4 FAP-associated) and 4 healthy controls. One hundred and one mRNAs resulted dysregulated, of which 98 in sporadic DTs and 8 in FAP-associated DTs, 5 were shared by both tumors. Twenty-six miRNAs were then validated by RT-qPCR in 23 sporadic and 7 FAP-associated DT samples matched with healthy controls. The qPCR method was also used to evaluate the CTNNB1 mutational status in sporadic DTs. The correlation between sporadic DTs and miRNA expression showed that miR-21-3p increased in mutated versus wild-type DTs, while miR-197-3p was decreased. The mRNA expression of Tetraspanin3 and Serpin family A member 3, as miR-21-3p targets, and L1 Cell Adhesion Molecule, as miR-197-3p target, was also evaluate. CTNNB1 mutations associated to miRNA dysregulation could affect the genesis and the progression of this disease and help histological diagnosis of sporadic DTs.