Aims To investigate molecular alteration and expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in hepatocellular carcinoma (HCC), and to evaluate the correlation between PTEN and cancer stem cell (CSC) markers and the prognostic value of these markers. Methods We evaluated changes of PTEN and CSC markers (CD133, epithelial cell adhesion molecule (EpCAM) and CK19) in 183 resection specimens by immunohistochemistry (IHC) and detected PTEN and phosphoinositide-3-kinase catalytic-alpha (PIK3CA) gene by fluorescence in situ hybridisation (FISH) in some specimens. Results PTEN and CD133, EpCAM and CK19 in 183 resection specimens were studied by IHC, and PTEN and PIK3CA genes were detected by FISH. PTEN expression was reduced in 91 HCC tissues (49.7%). There were 16 HCCs with PTEN deletion (51.6%). Comparison between PTEN IHC and FISH showed that the analysis was highly concordant (54/59, 91.5%). There were 19 HCCs with PIK3CA amplification. Deletion of PTEN was positively correlated with amplification of PIK3CA. Positive expression of CD133, EpCAM and CK19 was correlated with steatosis, moderate to poor differentiation, and so on. Reduction of PTEN expression was negatively correlated with positive expression of CD133, EpCAM and CK19. Reduced expression of PTEN (p=0.028) was an independent predictor for HCC recurrence and overall survival in HCC. PTEN−/CD133+ group had shorter OS and RFS time. Conclusions PTEN plays a key role in hepatocarcinogenesis and reduction of PTEN expression is related to increased expression of CD133, EpCAM and CK19, which is a useful tool to evaluate HCC prognosis and recurrence.

Extrahepatic metastasis of hepatocellular carcinoma (HCC) may cause a diagnostic problem. All 195 cases of histologic and immunostained sections were reviewed retrospectively in one center. The expression of arginase-1 (Arg-1), hepatocyte paraffin-1 (HepPar-1), glypican-3 (GPC-3), and α-Fetoprotein (AFP) was evaluated. Eighty cases of metastatic tumors of the liver were also collected to verify their effectiveness. Totally 151 cases had previous history of HCC, in whom 49 had history of liver transplantation. Forty-four cases were diagnosed as metastatic HCC at initial presentation. The most common extrahepatic metastatic sites were bone (57%), followed by lung, lymph node, etc. Around 19 cases were positive for 1 marker, 22 were positive for 2 markers, 95 were positive for 3 markers, and 59 were positive for 4 markers. With the number of antibody increased in the panel, the negative cases decreased. The sensitivity of ARG, GPC-3, HepPar-1, and AFP was 82.6%, 89.2%, 83.6% and 53.8%, and the specificity was 98.3%, 94.8%, 96.2% and 100%, respectively. These data suggest that the panel of ARG-1, GPC-3, HepPar-1 and AFP has a high sensitivity and specificity to differentiate HCC from non-HCC. This study indicated that HCC should be considered when diagnosing metastasis of unclear origin. It is recommended to use the panel of ARG-1, GPC-3, HepPar-1 and AFP to differentiate HCC from non-HCC in extrahepatic metastasis, because of their sensitivity and specificity, especially in poorly differentiated lesions.

The ubiquitin–proteasome system (UPS) plays a pivotal role in determining protein fate, regulating signal transduction, and maintaining cellular homeostasis. Protein ubiquitination, a key post-translational modification, is orchestrated by the sequential actions of three primary enzymes, ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin protein ligase (E3), alongside the regulatory influence of deubiquitinases (DUBs) and various cofactors. The process begins with E1, which activates ubiquitin molecules. Subsequently, E2 receives the activated ubiquitin from E1 and transfers it to E3. E3, in turn, recognizes specific target proteins and facilitates the covalent attachment of ubiquitin from E2 to lysine residues on the target protein. Among the E2 enzymes, ubiquitin-conjugating enzyme E2O (UBE2O) stands out as a unique E2–E3 hybrid enzyme. UBE2O directly mediates the ubiquitination of a wide array of substrates, including 5′-AMP-activated protein kinase catalytic subunit alpha-2 (AMPKα2), MAX interactor 1 (Mxi1), and v-maf musculoaponeurotic fibrosarcoma oncogene homolog (c-Maf), among others. In this narrative review, we will explore the structural characteristics of UBE2O and elucidate its molecular functions. Additionally, we will summarize recent advancements in understanding the role of UBE2O in various tumors, Alzheimer’s disease (AD), and metabolic diseases. Finally, we will discuss the potential of targeting UBE2O as a novel therapeutic strategy for the treatment of human diseases.

To describe the clincopathological features and evaluate risk factors of post-transplant lymphoproliferative disorder (PTLD) after allogeneic haematopoietic stem cell transplants (allo-HSCT), with comparison between paediatric and adult . Clinicopathological features of 81 cases of PTLD after allo-HSCT were analysed by histopatholgy, immunohistochemistry and in situ hybridisatioin. The cases included 58 males and 23 females with a median age of 26.7 years (range 6–55 years) and the PTLDs developed 1–60 months post-transplant (mean 5.9 months). The histological types indicated 10 cases of non-destructive PTLD, including 4 of plasmacytic hyperplasia, 5 of infectious mononucleosis and 1 of florid follicular hyperplasia. Fifty-six cases were polymorphic PTLD, and 15 were monomorphic PTLD, including thirteen of diffuse large B cell lymphoma, 1 of extranodal nasal type natural killer (NK)/T cell lymphoma and 1 of plasmablastic lymphoma. Foci and sheets of necrosis were observed in 31 cases. The infected ratio of Epstein-Barr virus (EBV) was 91.4%. Some cases were treated by reduction of immunosuppression, antiviral therapy, donor lymphocyte infusion or anti-CD20 monoclonal rituximab. Thirty-three cases died. Compared with that of adult, overall survival of paediatric recipient may be better. The first half year after allo-HSCT is very important for the development of PTLD. Type of PTLD, EBV infection and graft-versus-host disease are risk factors. The prognosis of PTLD is poor, and PTLD after allo-HSCT exhibits some features different from that after solid organ transplantation and some differences existing between adult and paediatric recipients.

Background: Invasive lobular carcinoma (ILC) of the breast has a unique metastatic pattern due to E-cadherin deficiency, with a predilection for peritoneal, gastrointestinal, and pelvic organ involvement. Ovarian metastasis from ILC is rare but can mimic primary ovarian cancer clinically and radiologically, leading to misdiagnosis and unnecessary radical surgery. This study aimed to summarize the imaging features of ovarian metastasis from ILC and analyze the causes of misdiagnosis, while highlighting the value of preoperative biopsy. Methods: Clinical and imaging data of six patients with pathologically confirmed ovarian metastasis from ILC were retrospectively analyzed. All six patients were female (age range 33–65 years), had a history of breast cancer (ILC subtype), and were found to have ovarian masses either during follow-up or at initial diagnosis. Imaging findings of the ovaries, peritoneum, and ascites were analyzed and compared with initial clinical diagnoses and pathological results. Results: Among the six patients, five were initially clinically misdiagnosed as having primary ovarian cancer and underwent unnecessary total hysterectomy with bilateral salpingo-oophorectomy. One patient (case 6) was correctly diagnosed via percutaneous biopsy of the omentum and skin nodules, which confirmed metastatic ILC, thereby avoiding unnecessary gynecological surgery. Imaging findings: All six patients had bilateral ovarian masses, appearing as solid or cystic-solid lesions. Peritoneal changes were observed in four cases. Ascites was present in five cases. Laboratory findings showed marked variability in CA125 levels (normal in three cases, elevated in three cases). Immunohistochemistry confirmed breast origin in all cases (GATA3+, PAX8−, E-cadherin−). In case 6, after four cycles of chemotherapy (albumin-bound paclitaxel + carboplatin + bevacizumab), follow-up CT demonstrated significant reduction in ovarian masses and regression of peritoneal and omental lesions. Conclusions: Ovarian metastasis from ILC is easily misdiagnosed as primary ovarian cancer without histologic confirmation, leading to unnecessary radical surgery. However, as demonstrated in case 6, percutaneous biopsy of accessible metastatic sites (omentum, peritoneum, or skin nodules) can establish the correct diagnosis and guide systemic therapy, thereby avoiding unnecessary surgery. In case 6, the ILC ovarian metastasis showed a favorable response to chemotherapy, but this single-case finding requires cautious interpretation as ILC is generally considered less chemosensitive than invasive ductal carcinoma. In patients with a history of breast cancer or with suspected metastatic disease, ILC metastasis should be included in the differential diagnosis of ovarian masses.