Nuclear expression of Ku70/80 is associated with CHEK2 germline mutations in breast cancer.

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.

Nuclear CK19-immunopositive pseudoinclusions as a new additional objective diagnostic feature of papillary thyroid carcinoma.

One of the key parameters in the diagnosis of papillary thyroid carcinoma (PTC) are true nuclear pseudoinclusions (NPs), which constitute invaginations of the cytoplasm into the nucleus. On the other hand, strong cytoplasmic expression of CK19 is a well-known attribute of PTC tumor cells. We analyzed NPs using CK19 immunohistochemistry in histological sections of 52 PTCs and seven noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs).

Fatty acids distribution and content in oral squamous cell carcinoma tissue and its adjacent microenvironment.

Squamous cell carcinoma of the oral cavity mucosa grows under conditions of poor oxygenation and nutrient scarcity. Reprogramming of lipid biosynthesis accompanies tumor growth, but the conditions under which it occurs are not fully understood. The fatty acid content of the serum, tumor tissue and adjacent tumor microenvironment was measured by gas chromatography in 30 patients with squamous cell carcinoma grade 1-3.

BRCA1 and PARP1 mRNA expression during progression from normal breast to ductal carcinoma in situ and invasive breast cancer: a laser microdissection study.

The contribution of DNA damage repair mechanisms to the progression of normal breast to ductal carcinoma in situ (DCIS) and invasive ductal carcinoma is largely unknown. The purpose of this report was to assess the mRNA expression levels of two important genes associated with DNA repair, BRCA1 and PARP1, in normal breast tissue, DCIS G1, G2 and G3, and co-existing adjacent invasive ductal carcinoma. BRCA1 and PARP1 mRNA expression was assessed in 32 ductal carcinomas in situ of the breast using a laser microdissection and pressure catapulting system and quantitative real-time PCR.

Immunohistochemical analysis of thymidylate synthase expression in gastric carcinoma: correlation with clinicopathological parameters and survival.

The correlation of thymidylate synthase (TS) expression in gastric cancers with tumor histology and prognostic or predictive information remains unclear. Most studies have involved Asian populations, with few conducted in European cohorts. Moreover, all published studies analyze TS expression using semi-quantitative methods.

E2F1/TS Immunophenotype and Survival of Patients with Colorectal Cancer Treated with 5FU-Based Adjuvant Therapy.

The predictive value of thymidylate synthase (TS) expression alone for 5FU-based treatment of colorectal cancer (CRC) has not been clinically confirmed. Little is known on the association of expression of E2F1, which controls the transcription of genes encoding proteins engaged in DNA synthesis including TS, and survival of patients with CRC. The purpose of this study is to assess the correlation between expression of both E2F1 and TS in CRCs and survival of patients administered adjuvant 5FU-based chemotherapy, in order to find a better predictor of treatment outcome than expression of TS or E2F1 alone.

Thymidylate synthase expression and p21(WAF1)/p53 phenotype of colon cancers identify patients who may benefit from 5-fluorouracil based therapy.

Background: Studies on the expression of thymidylate synthase (TS) in colorectal cancers (CRCs) have failed to provide unequivocal prognostic or predictive information. Here, we assessed the prognostic significance of TS expression in Astler-Coller stage B2 and C CRCs defined by a p21(WAF1)/p53 immunophenotype in patients subjected to 5-fluorouracil (5FU)-based adjuvant therapy.

Methods: A cohort of 189 CRCs was asssessed for TS, p21(WAF1) and p53 expression on tissue microarrays using immunohistochemistry, and associations with disease-free survival (DFS) and overall survival (OS) of the patients were assessed using univariate and multivariate analyses.

KRAS mutation testing in colorectal cancer as an example of the pathologist's role in personalized targeted therapy: a practical approach.

Identifying targets for personalized targeted therapy is the pathologist's domain and a treasure. For decades, pathologists have had to learn, understand, adopt and implement many new laboratory techniques as they arrived on the scene. Pathologists successfully integrate the results of those tests into final pathology reports that were, and still are, the basis of clinical therapeutic decisions.

Morphometric distinction of signet-ring cell adenocarcinoma cells from foamy macrophages in gastric endoscopic biopsies.

Aims: To distinguish signet-ring cancer cells from foamy macrophages in the small gastric endoscopic biopsies using objective morphometric measurements of nuclei.

Material And Methods: Using computerized image analysis, the mean nuclear area, length, breadth, perimeter and roundness were analyzed in histological sections of ten gastric endoscopic biopsies with signet-ring cell adenocarcinoma and four benign lesions with numerous foamy macrophages.

Results: Nuclei of signet-ring cell adenocarcinoma were significantly bigger than nuclei of foamy macrophages.

Reed-Sternberg cells in classical Hodgkin lymphoma in children seem to be predominantly oestrogen receptor α negative and oestrogen receptor β positive.

Oestrogen receptor α (ERα) is responsible for activation of gene transcription, while oestrogen receptor β (ERβ) serves as a negative regulator of ERα function. Since ER status is a prognostic and predictive factor in some cancers, we analysed the immunohistochemical expression of ERα and ERβ in Reed-Sternberg (RS) cells in paraffin-embedded lymph node specimens from 27 children with classical Hodgkin lymphoma (HL) in relation to histological type, clinical stage, age, and gender. Percentage of RS cells with positive nuclear reaction for the presence of ERα and/or ERβ was assessed.

Different CHEK2 germline mutations are associated with distinct immunophenotypic molecular subtypes of breast cancer.

Germline mutations in BRCA1 were already linked to basal-like subtype of immunophenotypic molecular classification of breast cancer (BC). However, it is not known whether mutations in other BC susceptibility genes are associated with molecular subtypes of this cancer. We tested the hypothesis that distinct mutations in another BC susceptibility gene involved in DNA repair, i.

Activation of NF-ĸB in leukemic cells in response to initial prednisone therapy in children with acute lymphoblastic leukaemia: relation to other prognostic factors.

Nuclear factor ĸB (NF-ĸB) is a transcription regulator of proliferation and cell death. Increased activation of NF-ĸB may be responsible for treatment failure in children with acute lymphoblastic leukaemia (ALL). This study aimed to assess changes in NF-ĸB activation in peripheral blood mononuclear cells prior to and after 6 and 12 h of prednisone administration in relation to age, initial WBC count at diagnosis and early treatment response in childhood ALL.

PARP-1 expression in breast cancer including BRCA1-associated, triple negative and basal-like tumors: possible implications for PARP-1 inhibitor therapy.

Despite ongoing trials of PARP inhibitors in the treatment of breast cancer (BC), the extent of poly(ADP-ribose)polymerase-1 (PARP-1) protein expression in BCs, which may influence treatment results, is not known. The purpose of this report is to assess expression of PARP-1 in BC including BRCA1-associated, triple negative (TN), and basal-like tumors. Immunohistochemistry with a PARP-1 antibody on tissue microarrays from 130 BRCA1-associated and 594 BRCA1-non-related BCs was used.

Expression of p21WAF1 in Astler-Coller stage B2 colorectal cancer is associated with survival benefit from 5FU-based adjuvant chemotherapy.

In several, but not all, previous studies, positive p21(WAF1) expression has been suggested as an indicator of a good prognosis in patients with stage III/IV colorectal cancer. However, it is not known whether the same is true for stage B2 patients. The purpose of this study is to assess the influence of p21(WAF1) expression in tumor cells on disease-free survival (DFS) and overall survival (OS) of Astler-Coller stage B2 and C patients with colorectal cancer who underwent 5-fluorouracil-based adjuvant chemotherapy.

Simultaneous assessment of p53 and MDM2 expression in leukemic cells in response to initial prednisone therapy in children with acute lymphoblastic leukemia.

Ineffective apoptosis is one of main causes of a treatment failure in childhood acute lymphoblastic leukemia (ALL). p53 plays a crucial role in triggering apoptosis of ALL in response to prednisone treatment. MDM2 is the endogenous inhibitor of apoptosis that downregulates the functional activity of p53 protein.

Immunophenotypic predictive profiling of BRCA1-associated breast cancer.

The immunophenotypic predictive profile of BRCA1-associated cancers including major predictive markers, i.e., PARP-1, EGFR, c-kit, HER-2, and steroid hormones (ER/PR) that may have therapeutic relevance has not yet been reported in a comprehensive study.

Effects of recombinant human growth hormone (rhGH) replacement therapy on detailed immunologic parameters in somatotropine--deficient paediatrics patients prior and after 6 months of rhGH treatment.

Objective: This study aims at assessing how recombinant human growth hormone treatment of children and young people suffering from isolated growth hormone deficiency affects some selected parameters of the immune system: a percentage of lymphocytes, granulocytes, monocytes, concentrations of A, G, and M immunoglobulins, a percentage of T lymphocytes divided into subpopulations CD4 and CD8, a percentage of NK and B lymphocytes, and phagocytic activity of granulocytes and monocytes.

Materials And Methods: The study comprised 30 children and young people aged 4.2-18 years with isolated growth hormone deficiency both prior to and 6 months after rhGH (recombinant human growth hormone) treatment with a dose of 0.

Prognostic significance of morphometric parameters of nucleoli and nuclei of invasive ductal breast carcinomas.

The aim of this study was to evaluate associations between seven morphometric parameters of the nucleoli and nuclei of methyl green and pyronin Y (MG-PY) stained tumour cells of invasive ductal breast carcinoma with relapse-free survival (RFS) and overall survival (OS) time. Histological sections from 150 invasive ductal breast cancers were stained with MG-PY and the following parameters were evaluated by computer image analysis: the nucleolar area, long to short nucleolar axis ratio, nucleolar shape parameter assessing the degree of nucleolar roundness, long to short nuclear axis ratio, number of nucleoli in the nucleus and the percentage of the nuclear cross-section surface area occupied by the nucleoli. A statistically significant association between a nucleolar shape polymorphism and the number of nucleoli in the nuclei of tumour cells and the RFS but not OS was found in the entire group of patients as well as patients with axillary lymph node metastases.

Mutational analysis of CDKN2A gene in a group of 390 larynx cancer patients.

CDKN2A gene belongs to the genes involved in cell cycle regulation. When is absent or inactivated by mutation or promoter hypermethylation a cell may undertake an uncontrolled proliferation. Inactivation of CDKN2A gene is observed in many human malignancies, including larynx cancer.

Good early treatment response in childhood acute lymphoblastic leukemia is associated with Bax nuclear accumulation and PARP cleavage.

Background: Bax activation and intracellular redistribution as well as its prognostic significance during steroid-induced apoptosis of leukemic cells in childhood acute lymphoblastic leukemia (ALL) remain a matter of controversy. The purpose of this study was to assess time-resolved changes in Bax activation and its intracellular distribution as well as the percentage of apoptotic cells evaluated by PARP cleavage in response to prednisone treatment in childhood ALL.

Material/methods: The study comprised 43 children with de novo ALL.

Nuclear thymidylate synthase expression in sporadic colorectal cancer depends on the site of the tumor.

Colorectal carcinoma (CRC) is a heterogeneous disease with specific epidemiological, pathological, molecular, and clinical characteristics that depend on the location of the tumor relative to the splenic flexure. Thymidylate synthase (TS) is a major target of 5-fluorouracil-based chemotherapy for CRC and high expression of this enzyme in tumor cells can influence the effect of therapy. We examined differences in TS protein expression in nuclei of tumor cells between CRCs located proximal and distal to the splenic flexure.

In vitro assessment of adhesion molecules expression by human endothelial cells cocultured with c-erbB2-positive and c-erbB2-negative breast carcinoma cell lines.

Objective: In vitro assessment of ICAM-1, VCAM-1 and P-selectin expression on endothelial cells cocultured with c-erbB2-positive (SK-BR-3) and c-erbB2-negative (MCF-7) breast carcinoma cell lines.

Material And Methods: The expression of adhesion molecules was determined by immunofluorescence, and measured by a laser scanning cytometer.

Results: Endothelial cells cocultured with c-erbB2-negative breast carcinoma cell line--as compared to endothelial cells cultured without carcinoma cells--demonstrated an increase in the expression of VCAM-1 and P-selectin, a decrease in the expression of ICAM-1, and an increase of the maximal pixel intensity of ICAM-1, VCAM-1 and P-selectin orange fluorescence.

Genetic contribution to all cancers: the first demonstration using the model of breast cancers from Poland stratified by age at diagnosis and tumour pathology.

The aim of the study is to verify the hypothesis that genetic polymorphisms are associated with the predisposition to all malignancies. Using as a model breast cancers from the homogenous Polish population (West Pomeranian region) after stratification of 977 patients by age at diagnosis (under 51 years and above 50 years) and by tumour pathology (ductal cancers--low and high grade, lobular cancers, ER-positive/negative) we tested this hypothesis. Altogether 20 different groups of breast cancer cases have been analyzed.