Membrane expression of trail receptors DcR1 and DcR2 in the normal endometrium, endometrial atypical hyperplasia and endometrioid endometrial cancer.

We aimed to evaluate the membrane expression of DcR1 and DcR2 in the normal endometrium (NE), endometrial atypical hyperplasia (EAH) and endometrioid endometrial cancer (EEC). The study comprised 101 patients: 20 NE, 14 EAH and 67 EEC. Membrane expression of DcR1 and DcR2 was examined and presented as total score (TS). The membrane expression of both DcR1 and DcR2 was more common in EEC than in NE (p < 0.001; p < 0.001). A strong correlation was found between type of endometrial tissue (NE/EAH/EEC) and the TS of DcR1 (p = 0.001) and DcR2 (p < 0.001). In EEC, the TS of DcR1 and DcR2 was not related to grading and survival. The TS of DcR1 negatively correlated with staging (p = 0.018), but DcR2 did not. The membrane expression of decoy receptors for TRAIL DcR1 and DcR2 is greater in NE than EEC. In EEC patients, membrane expression of DcR1 and DcR2 are not independent predictors of survival.

Membrane expression of the death ligand trail receptors DR4 and DR5 in the normal endometrium, endometrial atypical hyperplasia and endometrioid endometrial cancer.

To assess membrane expression of DR4 and DR5 in the normal endometrium (NE), endometrial atypical hyperplasia (EAH) and endometrioid endometrial cancer (EEC), the study examined 101 patients: 20 NE, 14 EAH and 67 EEC. The expression of DR4 and DR5 was examined and presented as the total score (TS). DR4 expression was seen in 18 NE, 11 EAH and 10 EEC. DR5 expression was seen in 20 NE, 13 EAH and 21 EEC. A strong correlation between type of endometrial tissue and TS of both receptors was identified. In EEC TS of DR4 and DR5 was not related to grading, staging or survival. Malignant transformation in the endometrium is related to reduction of membrane DR4 and DR5 expression. The level of membrane staining of the receptors in EEC is not dependent on grading and staging, and is not sufficient to predict survival in EEC patients.

Construction of a tissue microarray with two millimeters cores of endometrioid endometrial cancer: factors affecting the quality of the recipient block.

The tissue microarray (TMA) method currently is not used to render a primary diagnosis of cancer, but its scientific value has been proved in studies of various cancer types. TMA technology still is not used often for uterine tumors, however. We investigated the repeatability of histological diagnosis of endometrioid endometrial cancer (EEC) using conventional histology and TMA using 2 mm cores. We examined EEC tissues from 171 patients. Formalin fixed, paraffin embedded tissue donor blocks from EEC specimens were selected and examined histologically. Duplicate 2 mm tissue cores were inserted into a TMA recipient block. EEC tissues were examined as hematoxylin-eosin stained sections from the TMAs. EEC tissue was identified in the TMAs in 158 cases (92.4%) and not found in 13 cases (7.6%). On the TMA slides, both EEC positive cores were identified in 129 cases (75.4%), but only one core in 29 cases (17.0%). Among 342 biopsies of the donor blocks (each case in duplicate), EEC was found in 287 cases (83.9%) using the TMA: 124/146 (84.9%) with superficial infiltration, 153/178 (86.0%) with deep myometrial infiltration, and 10/18 (55.6%) without myometrial infiltration. We concluded that two 2 mm tissue cores from a biopsy of a donor block inserted into a TMA recipient block were sufficient to diagnose EEC in more than 90% of cases. EEC was identified in the TMAs with similar frequency with respect to superficial and deep myometrial infiltration. Cases without myometrial infiltration were identified less often.

An extremely rare presentation of relapse in endometrioid endometrial adenocarcinoma: isolated metastases to the tibia and humerus. Case report and review of the literature.

In endometrial carcinoma patients, metastases to bones are rare and isolated metastases to extremities are extremely rare. We describe the case of a 59-year-old patient who underwent surgery followed by adjuvant radiotherapy due to endometrioid endometrial adenocarcinoma (grade 2, FIGO Stage II). After intervals of nine and 18 months respectively, she was diagnosed with metastatic tumours located in the right tibia and in the left humerus. The metastases were confirmed by biopsy. Following irradiation of metastatic lesions, the relief of symptoms was observed, and the patient remains under observation. We conclude that patients presenting a history of endometrial carcinoma with chronic pain in the extremities should be carefully evaluated, because although extremely rare, the carcinoma can metastasize to bones. Treatment of bone metastasis from endometrioid endometrial carcinoma by irradiation may increase quality of life and prolong survival.

Maspin and Nm23-H1 expression in colorectal cancer.

The aim of the study was to analyze the expression of Nm23-H1 and maspin proteins in a series of colorectal adenocarcinoma and to assess their applicability as prognostic factors in this type of cancer. 102 specimens of colorectal carcinoma were analyzed by immunohistochemistry with the use of anti-Nm23-H1 and anti-maspin monoclonal antibodies. Cytoplasmic expression of Nm23-H1 and maspin was found in 90 of all investigated cases. In 60 cases maspin protein was found also in nucleus. Medium/high Nm23-H1 cytoplasmic expression level was associated with tubular type of adenocarcinoma with deeper invasion of cancer into intestinal wall (T3, T4) and presence of vascular invasion. Medium/high expression level of maspin was connected uniformly with bad prognostic features: low differentiation of tumors (G3), deeper invasion of cancer (T3, T4) presence of nodular and distant metastases, higher Astler-Coller stage (C1, C2, D) and presence of vascular invasion. No statistically significant associations between presence of nuclear maspin expression and any clinicopatological and biological features were stated. Cytoplasmic medium/high expression level of maspin but no Nm23-H1 and no presence of maspin nuclear expression was found as independent bad prognostic factor in the investigated group of patients. Measurement of level and cellular pattern of maspin expression could be valuable for predicting disease course in patients suffering from colorectal cancer.

Astonishingly rapid growth of malignant cystosarcoma phyllodes tumor in a pregnant woman--a case report.

There are very few reports concerning the presence of malignant cystosarcoma phyllodes (CSP) in breasts of pregnant women. In the hereby described case, a 28-year-old woman presented in our department with huge (18 x 11 x 8 cm) tumor of left breast, 2 weeks after labor. The patient discovered a tumor in 34th week of pregnancy, 6 weeks before labor. Histopatholgic examination of excised tumor revealed the presence of malignant CSP tumor. Simple mastectomy was proposed to patient as a best treatment modality. However, the patient refused. She underwent excision of tumor bed (2-cm tumor-free margin was achieved). Despite insufficient treatment, she remains free of disease 20 months after the wide excision of breast malignancy. It is not known how pregnancy influences prognosis of patients with malignant CSP. Lack of such information prompted us to describe the clinical course of our patient.

Cyclin D1 protein and CCND1 gene expression in colorectal cancer.

AIMS: To report the expression of cyclin D1 protein and its gene in a series of colorectal adenocarcinoma. METHODS: One hundred and eleven specimens of colorectal carcinomas and adjacent normal colorectal mucosa were investigated by staining with a monoclonal antibody against cyclin D1 and by RT-PCR. RESULTS: Expression of CCND1 gene was found in 54 out of 111 cases of colorectal cancers, while in normal mucosa the expression of this gene was not observed. Cyclin D1 protein expression was checked in the same group of adenocarcinoma cases. Presence of this protein was observed in 69 cases and for 43 of them also expression of its gene was found. Dependence between the presence of protein and the gene expression was statistically significant (p=0.0002). In the group of cases where CCND1 gene expression was detected, high level of its protein expression was found in 20 cases. The CCND1 gene expression was associated with metastases to lymph nodes (p=0.0181) and also with distant metastasis (p=0.0204). CONCLUSIONS: The combined measurement of both the gene and its protein product, is an important contribution to the study of molecular markers in histological material.

Expression of the p65 gene in patients with colorectal cancer: comparison with some histological typing, grading and clinical staging.

AIMS: P65 protein/gene is a potential, non-specific tumour marker expressed by different types of neoplasms. In this study p65 gene expression was estimated in a group of colorectal cancers and compared with some histological features, grading and clinical staging of the neoplasms to assess its role as a prognostic marker for colorectal cancer. METHODS: 109 pairs of frozen samples of colorectal carcinomas and adjacent normal colorectal mucosa and four samples of tissue from patients without neoplastic diseases were analysed by means of RT-PCR. RESULTS: Expression of p65 gene was found in 51 out of 109 cases of colorectal cancers. For 19 of them expression of examined gene was observed both in cancer and corresponding healthy mucosa. p65 Gene expression was associated with more advanced tumours (T3, T4; p=0.0003) with metastases to lymph nodes (N1, N2; p=0.0003) and distant metastases (p=0.0005). We did not find association between the age, gender, tumour localization, histological type and p65 gene expression. CONCLUSIONS: p65 Gene expression in primary tumour tissue is associated with poor prognosis for the patients with colorectal cancer in this series.

HMGI(Y) gene expression in colorectal cancer: comparison with some histological typing, grading, and clinical staging.

We investigated HMGI(Y) gene expression in 81 pairs of frozen samples obtained from colorectal carcinomas and adjacent normal colorectal mucosas and in four samples from colorectal mucosa from patients without neoplastic diseases. In this group, HMGI(Y)-positive/-negative expression was compared with some histological features, grading, and clinical staging of neoplasms investigated to assess its potential role as a prognostic marker for colorectal cancer. Expression of HMGI(Y) gene was found in 51 of 81 cases of colorectal cancers, while, in normal mucosa, expression of this gene was not observed. HMGI(Y) gene expression was associated with more advanced tumors (T3, T4) and metastases to lymph nodes (N1, N2). The most interesting finding was that expression of this gene correlated with distant metastases. HMGI(Y) gene expression was detected in all cases classified as M1 (n = 19, p = 0.0008). We did not find any association between age, gender, tumor localization, histological type and this gene expression.

P21 (WAF1) expression in colorectal cancer: correlation with P53 and cyclin D1 expression, clinicopathological parameters and prognosis.

P21 (WAF1), P53 and cyclin D1 belong to the cell cycle-regulating family of proteins, and the loss of activity of proteins P53 and P21 (WAF1) seems to be one of the most important regulatory mechanisms of carcinogenesis in colorectal cancer. The purpose of this study was to assess the relationship between P21 (WAF1), P53 and cyclin D1 immunoreactivity, and to evaluate the prognostic significance of their expression. Tissue sections from 122 paraffin-embedded colorectal carcinomas were immunostained with monoclonal antibodies. Positivity for P21 (WAF1) was found in 48 cases (39%), positivity for P53 in 96 cases (70%) and positivity for cyclin D1 in all the cases (100%). Statistical analyses revealed a statistically significant inverse correlation between P53 and P21 (WAF1)-immunopositivity and between P21 (WAF1)-immunopositivity and the degree of cyclin D1-immunopositivity, as well as an inverse correlation between P21 (WAF1) expression and clinical stage. In univariate analysis, down-regulation of P21 (WAFI) expression was associated with poor prognosis, but multivariate analysis did not confirm its independent prognostic significance. In Cox's analysis only regional lymph node invasion and hepatic metastases were proven as independent prognostic parameters. Our investigation results suggest that in colorectal cancer, the induction of P21 (WAF1) may occur mostly in a P53-dependent pathway. P21 (WAF1), as the main cyclin-dependent kinase (CDK)-inhibitor, may also inhibit the activity of cyclins such as cyclin D1.

Comparative evaluation of the expression of cell cycle regulating proteins: cyclin D1, P53 and P21 (WAF1) in colorectal cancer.

Cyclin D1, P53 and P21 (WAF1) are cell cycle regulating proteins, playing a crucial role in oncogenesis of a large number of human malignancies, and loss of activity of P53 and P21 (WAF1) proteins seems to be one of the most important regulatory mechanisms of carcinogenesis in colorectal cancer. To find out their mutual relations we investigated the expression of cyclin D1, P53 and P21 (WAF1) in 122 colorectal cancers by immunohistochemistry. Positivity for cyclin D1 was found in all the cases (100%), positivity for P53 in 96 cases (70%) and positivity for P21 in 48 cases (39%). Statistical analysis revealed a statistically significant inverse correlation between P53 and P21 (WAF1)-immunopositivity and also between P21 (WAF1)-immunopositivity and the degree of cyclin D1-immunopositivity. These data suggest that in colorectal cancer induction of P21 (WAF1) may occur mostly in a P53-dependent pathway. Wild-type P53, which is undetectable by immunohistochemistry, induces transcriptionally P21 (WAF1) and in tumours it may cause its accumulation, while mutations of the P53 may result in a sufficient increase of intracellular protein having no ability to transactivate P21 (WAF1). Moreover P21 (WAF1) as the main cyclin-dependent kinases (CDKs) inhibitor may also inhibit the activity of the cyclins, thus overexpression of P21 (WAF1) may result in reduced level of cyclin D1.