Polish Journal of Pathology最新文献

Ku70/80 protein inhibitors reduce the repair of DNA double-strand breaks via the Ku70/80 pathway, so they can be used to treat cancers with Ku70/80 overexpression. Since the association of Ku70/80 with germline CHEK2 mutations in breast cancer is unknown, in this study we evaluated the expression of Ku70/80 in breast cancers with germline CHEK2 mutations. Immunohistochemistry with a Ku70/80 antibody on tissue microarrays from 225 CHEK2-associated breast cancers was used and automatically assessed with computerized image analysis. We report that the vast majority of breast cancers expressed high level of nuclear Ku70/80 and a small percentage of tumors (3.5%) were negative for Ku70/80 expression. There was a significant difference between the nuclear Ku70/80 expression in CHEK2-associated vs. CHEK2-non-associated breast cancers in all tumors (p = 0.009), and in the estrogen receptor (ER) positive subgroup of breast cancers (p = 0.03). This study is the first reporting an association of Ku70/80 expression with CHEK2 germline mutations in breast cancer. The results suggest that evaluation of Ku70/80 expression in breast cancer may improve the selection of breast cancer patients for Ku70/80 inhibitor therapy, and point to CHEK2-associated breast cancer and a subset of ER-positive breast cancer as potential suitable targets for such therapy.

In cancer research, the mechanism underlying the immune response to a tumour has been of great interest. In this study, we investigated the role of CD274 (programmed cell death-ligand 1 - PD-L1) and CD3+ tumour-infiltrating lymphocytes (TILs) in the prognosis of advanced colorectal cancer (CRC) patients treated with neoadjuvant chemotherapy. We retrospectively examined primary tumour specimens from stage III/IV CRC patients operated on between 2008 and 2018. We found a significant association between these biomarkers and pT stage (PD-L1, p = 0.020; CD3+TILs, p = 0.025), tumour grade (PD-L1, p = 0.005; CD3+TILs, p = 0.004), positive surgical margin (PD-L1, p = 0.001; CD3+TILs, p = 0.001), MSI (PD-L1, p < 0.001; CD3+TILs, p < 0.001), etc. We also discovered that these biomarkers are independent risk factors for MSI (PD-L1, OR = 1.84 [1.27-4.02], p = 0.003; CD3+TILs, OR = 1.92 [1.31-4.35], p = 0.008). Univariate analysis results revealed that patients with high PD-L1, low CD3+TIL, and both showed poor relapse-free survival (RFS) and poor overall survival (OS) (PD-L1: RFS, p = 0.008 and OS, p = 0.001; CD3+TILs: RFS, p = 0.003 and OS, p = 0.005; PD-L1 and CD3+TILs: RFS, p < 0.001 and OS, p < 0.001). The results of the multivariate analysis showed that the combined use of high PD-L1 and low CD3+TILs was a better predictor of poor RFS and OS (PD-L1 and CD3+TILs: RFS, hazard ratio - HR, = 2.85 [95% CI: 1.36-3.84], p < 0.001); OS, HR = 2.74 [1.32-3.71], p < 0.001). We also found a high PD-L1 parameter as another independent overall and relapse-free survival parameter. Our findings suggest that a combination of high PD-L1 and low CD3+TIL can reliably predict poor survival in CRC patients receiving chemotherapy. Therefore, these biomarkers may be promising for the planning and execution of appropriate targeted therapies.

Thyroid neoplasms are the most common endocrine malignancies. ZIP4 is an intramembranous zinc trans membrane protein. Zinc plays a central role in the activation of transcription factors, and zinc transporters. This affects tumour migration, invasion, and cell proliferation. ZO-1 and Claudin-1 are important tight junction proteins whose amounts increase and decrease in various cancers. In this study, we aimed to investigate the expression of ZIP4, ZO-1, and Claudin-1 in thyroid tumours and the relationship of this expression with tumour types and prognostic parameters. ZIP4, ZO-1, and Claudin-1 were studied in all cases by immunohistochemical and Real-Time PCR methods. ZIP4 and Claudin-1 tended to be expressed more in cases with tumours, while ZO-1 in cases with and without tumours. Expression of ZIP4 and Claudin-1 by real-time polymerase chain reaction showed a significant difference between histological subtypes, and this difference was not observed with ZO-1. It was observed that the presence of metastasis increased with the expression of ZIP4 and Claudin-1, and there was no significant change with ZO-1. We think that Claudin-1 and ZIP4 expression can be used as an important marker in terms of showing poor prognosis and susceptibility to metastasis in thyroid tumours, and in developing targeted therapy.

According to the latest data provided by Globocan 2020, the incidence of colorectal cancer ranks third, after lung cancer and breast cancer, becoming a more and more important global health issue. Of the cases diagnosed with colorectal cancer, more than 25% are diagnosed in the metastatic stage, with the presence of secondary tumors more frequently in the liver, lung and bone. Skin metastases from colorectal cancer are still rare today (< 4%). We want to present a rare, unique case in our department of a 74-year-old patient diagnosed 9 years ago with a malignant rectal tumor who, after a disease-free period of approximately 8 years and a half, developed multiple skin metastases of rectal adenocarcinoma.

S100 calcium-binding protein A16 (S100A16) has previously been reported to play a role in tumor cells. Nevertheless, the role that S100A16 played in nephroblastoma cells remains obscure. The expression of S100A16 and DEPDC1 were detected via RT-q PCR and western blotting. Cell transfection was performed to overexpress DEPDC1 or interfere S100A16. CCK8 was applied for the assessment of cell viability. The apoptotic level and the capabilities of WiT49 cells to proliferate, invade and migrated were appraised utilizing Tunel, colony formation Transwell, and wound healing, separately. The angiogenesis was estimated through tube formation assay. Co-immunoprecipitation (CO-IP) was performed to examine the targeted binding of S100A16 to DEPDC1. The contents of PI3K/Akt/mTOR pathway-related proteins were resolved by virtue of western blot. S100A16 and DEPDC1 expression levels were significantly increased in nephroblastoma cell lines. S100A16 deletion suppressed nephroblastoma cell proliferative, invasive, migrative and angiogenetic capabilities but facilitated the apoptotic level. Moreover, S100A16 could bind DEPDC1, DEPDC1 overexpression partially reversed the inhibitory effect of S100A16 interference on nephroblastoma cell. DEPDC1 overexpression also partially counteracted the suppressive impacts of S100A16 interference on PI3K/Akt/mTOR pathway-related proteins. S100A16 synergistic with DEPDC1 promotes the progression and angiogenesis of nephroblastoma cell through the PI3K/Akt/mTOR pathway.

Calcifying epithelioma of Malherbe, also known as pilomatricoma or pilomatrixoma, mostly arises in the matrix hair follicle. It generally affects the head and neck, upper extremities, and trunk, with the lower extremities being a rare exception. We hereby present a case of a 31-year-old male patient who presented with a small, firm, subcutaneous mass over the left malleolus, which was provisionally diagnosed as lipoma. Surgical excision was performed, and the histopathology report revealed it to be pilomatricoma of the left malleolus.

Prostate cancer (PC) is one of the most common cancers in males. A significant proportion of PCs bear TMPRSS2-ETS translocation and overexpress ERG transcription factor, allowing classification into ERG+ and ERG- groups, which differ in several features including the tumor microenvironment. The aim of the study was to verify whether they differ in expression of the miRNA in the microenvironment. The material consisted of 150 radical prostatectomies. Immunohistochemistry (IHC) for ERG was done using a routine method. FISH for TMPRSS2-ETS translocation was done with a ZytoLight SPEC ERG/TMPRSS2 TriCheck Probe. From each case, a representative section was selected, and tumor and non-tumor were microdissected with the LMD7000 device. RNA was isolated using the RNeasy Mini Kit system (Qiagen) and miRNA libraries were prepared with the NEBNext Multiplex Small RNA Library Prep Set for Illumina and their sequencing was performed on the NexSeq 500. Statistical analysis was done with Statistica and R software. When analyzing the expression of miRNAs some differences could be seen, but after correction for multiple comparisons was applied, these were found to be non- significant.

Squamous cell carcinoma (SCC) of the esophagus and adenocarcinoma of the esophago-gastric junction (AEG) are diseases with poor prognosis. Despite radical surgery having been carried out, many patients are at risk of cancer recurrence, especially with the presence of metastases in the lymph nodes. The study involved 60 patients suffering from SCC and AEG who had lymph nodes surgically removed between 2012 and 2018. Only lymph nodes with N0 status were subjected to immunohistochemistry examination. Histopathological criteria were used for the diagnosis of micrometastases (MM), defined as tumor cells or cell clusters of 0.2-2 mm diameter in the lymph node and tumor cell microinvolvement defined as free-floating neoplastic cells or cell clusters within the sub-capsular sinus or intramedullary sinuses of the lymph node. A total of 1130 lymph nodes were removed during surgery, with an average of 22 lymph nodes per patient (range 8-58). Micrometastases were found in 7 (11.66%) patients: 6 (10.0%) with AEG and 1 (1.66%) with SCC, representing a statistically significant difference p = 0.017. Multivariate analysis of the study group did not confirm the dependence of the MM on the T features ( p = 0.7) or G ( p = 0.5). In a Cox regression analysis, MM were not a risk factor for death, HR: 2.57 (0.95; 7.00), p = 0.064. There was no difference in overall survival for patients with MM (N (+)) and those without (N0), p = 0.055, but there was a statistically significant difference in time of relapse between patients with and without MM ( p = 0.049). Patients with the N (+) status are at high risk of cancer recurrence, and therefore we believe that complementary treatment should be considered in this group.

Prognostic factors in Merkel cell carcinoma (MCC) are scarce. Tumour budding (TB) has been shown to have a prognostic role in different cancers but has not been explored in MCC. We aimed to determine if TB influences survival in MCC. We performed a retrospective evaluation of 45 cases of MCC in a cancer centre. This included a survival analysis involving TB in patients with MCC, and we searched for variables associated with TB. The mean age of the patients was 69 years. Histologically, the average Breslow was 11.36 mm, and the mean mitotic rate was 31.9 mitoses/mm2. The diagnosis was made in clinical stages I and II in 40% of cases, 22.2% in stage III, and 37.8% in stage IV. Tumour budding was low ( 10 buds/0.785 mm2) in 24.4%. There were no clinical or pathological features associated with high TB. Among the prognostic factors for 5-year survival, we found that tumour size and clinical stage were statistically associated with survival (p = 0.031 and 0.021), but TB was not. No clinical or pathological characteristics of MCC are associated with any degree of TB. Tumour budding does not influence overall survival.