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Determination of oestrogen receptor alpha (ER) represents at present the most important predictive factor in breast cancers. Data of ours and of other authors suggest that promising predictive/prognostic factors may also include pS2, metallothionein (MT) and CD24. Present study aimed at determining prognostic and predictive value of immunohistochemical determination of ER, pS2, MT, and CD24 expression in sections originating from 104 patients with breast cancer. An univariate and multivariate analysis was performed. Both univariate and multivariate analyses demonstrated that cytoplasmic-membranous expression of CD24 (CD24c-m) represents a strong unfavourable prognostic factor in the entire group and in most of the subgroups of patients. In several subgroups of the patients also a prognostic value was demonstrated of elevated expression of pS2 and of membranous expression of CD24. Our studies demonstrated that all patients with good prognostic factors (higher ER and pS2 expressions, lower MT expression, CD24c-m negativity) survived total period of observation (103 months). The study documented that cytoplasmic-membranous expression of CD24 represented an extremely strong unfavourable prognostic factor in breast cancer. Examination of the entire panel of the studied proteins permitted to select a group of patients of an exceptionally good prognosis. [ABSTRACT FROM AUTHOR]

Purpose: To assess the prognostic significance of clinico-pathological factors, especially histological parameters of new Jass classification, following sphincter-sparing total mesorectal excision (TME) for high-risk rectal cancer. Material and methods: Forty-five consecutive patients treated with curative intent in 1998-1999 due to rectal cancer in Dukes stage B and C were studied prospectively. All of them underwent anterior resection with TME technique. Prognostic value was evaluated by the impact on five-year recurrence-free survival (RFS) in uni- and multivariate analysis. Only factors significant in univariate analysis entered the multivariate regression model. P value <0.05 was stated as a significance limit. Results: Regarding traditional clinico-pathological factors patient age, tumor site, differentiation grade, mucinous histology and the extent of direct tumor penetration did not significantly affect survival rates. Only the lymph nodes status was associated with prognosis with statistical importance (negative vs positive, RFS: 53.8±10.0% vs 26.3±10.4%, respectively). Considering the additional parameters of Jass classification the character of invasive margin of the tumor did not reveal the important predictive value although the lymphocytic tumor infiltration was significantly related to patient outcome (presence vs absence, RFS: 63.6±15.2% vs 37.5±8.7%, respectively). In multivariate analysis the only one statistically important and independent predictive parameter was the lymph nodes status. Conclusions: Lymph nodes metastases remain the most important prognostic factor after anterior resection with TME for Dukes B and C rectal cancer. From variables included into Jass classification the absence of lymphocytic infiltration of the tumor can be helpful to identify patients with enhanced risk of oncological relapse. [ABSTRACT FROM AUTHOR]

Background: Tamoxifen, used in breast cancer treatment, competitively inhibits estrogen receptor (ER) and also demonstrates direct antiproliferative effect on cancer cells even in ER lacking cancer tissue. However its molecular mechanism of action is still unclear, Material and Methods: We exposed on tamoxifen 11 ovarian cancer cell lines, including well-documented platinum-sensitive and platinum-resistant ones, and studied tamoxifen-, cisplatin-sensitivity and expression of ERalpha and beta., Results: We observed: no correlation between TAM-sensitivity and ERalpha and ERbeta expressions, no correlation between TAM influence on cisplatin-sensitivity and ERalpha and ERbeta expressions, increase of ERbeta expression after TAM-exposure in 3 cell lines; decrease in the 1 line, no TAM-exposure influence on ERalpha expression and increase of 1050 for cisplatin after TAM-exposure in 5 (45%) cell lines. These results show ovarian cancer cells being affected by TAM have different platinum sensitivity, Conclusions: Our data suggests that ovarian cancer cells platinum-sensitivity are not linked with ER expressions. We claim the necessity of seeking some TAM predicting factors, using DNA microarrays.

Objective: The aim of the study was to identify factors associated with worse physical and emotional functioning of breast cancer survivors with upper extremity lymphedema., Methods: 1250 sets of questionnaires consisting of WHO-DAS II, EORTC QLQ-C30, EORTC QLQ-BR23 and GHQ-30 were mailed to women who underwent a breast cancer surgery at the Lower Silesian Oncology Center in Poland between January 1998 and December 2005., Results and Conclusions: The response rate was 33.47%. 117 women were included into a lymphedema group and 211 into a group without this complication. Women with lymphedema were more disabled (overall disability (DAS) score 39.78 versus 34.67; p<0.001), reported symptoms from the upper extremity (shoulder or arm pain and difficulties in arm movement) and from the operated breast (pain and swelling) 2-3 times more often, experienced poorer quality of life (global quality of life (QOL) score 0.50 versus 0.57; p=0.005) and higher psychological distress (GHQ score 10.61 versus 8.01; p=0.007) in comparison to breast cancer survivors without lymphedema. The factors associated with higher DAS score, higher GHQ score and lower QOL score in women with lymphedema were as following: pain in the upper limb (mainly shoulder and arm), pain in operated breast, difficulties with arm movement, localization of lymphedema within the hand or in operated breast, a history of dermatolymphangitis and of receiving chemotherapy. Severity of lymphedema, younger age, BMI and localization of lymphedema within the dominant limb were not considerably related to worse outcomes in these women.

Linker histones H1 are key modulators of chromatin structure. Tightness of their binding to DNA is regulated by posttranslational modifications. In this study we have analyzed posttranslational modifications of five major variants of H1 in human tissue - H1.0, H1.2, H1.3, H1.4, and H1.5. To improve sequence coverage, tryptic peptides of H1 were separated by HPLC and the individual fractions were analyzed using a peptide on-chip implementation of nanoelectrospray (TriVersa), coupled to a linear ion trap-orbitrap hybrid instrument. For quantitative analysis of lysine methylation, ionization efficiencies of methylated and nonmethylated peptides were determined using synthetic peptides. Our analysis revealed that monomethylation of lysine residues alongside with phosphorylation of serine and threonine residues is the major modification of H1 in tissue. We found that most prominent methylation sites are in the N-terminal tail and the globular domain of H1. In the C- terminal domains we identified only few and less abundant methylation sites. Quantitative analysis revealed that up to 25% of H1.4 is methylated at K-26 in human tissues. Another prominent methylation site was mapped to K-27 in H1.5, which resembles the K-26 site in H1.4. In H1.0 five less abundant (<1% of H1.0) sites were identified. Analysis of patient matched pairs of cancer and adjacent normal breast demonstrated high variation in H1 methylation between individuals.

Unlabelled: Well-organised mammography screening programme can significantly reduce the breast cancer mortality However, changes in mortality rates take a long time thus some early indicators are usually used to monitor the effectiveness of the programme. If these operational objectives are accomplished then the programme can replicate the mortality reduction achieved in randomised trials., The Aim of This Study: To evaluate the quality of breast cancer screening programme in the region of Lower Silesia during the first year of its operating., Material and Methods: Centrally organised breast cancer screening has been introduced since the beginning of the year 2007. This population-based programme is designed for women aged 50-69. Females undergoing treatment or being followed-up due to breast cancer are not invited. Screen-film two-view mammography without clinical examination is used as a screening test which is to be performed every two years. The second level diagnostic tools are breast clinical examination and additional imaging (mammography and ultrasound). Following further assessment women are referred to the examination at the routine round length of the programme, at the less interval (short-term recall) or biopsy procedures. Quality assessment was done via early indicators according to the European guidelines., Results: The attendance rate was 41% (79,143 women screened within 192,613 eligible population for one year). Technical repeat rate, further assessment rate, and short-term recall rate were: 0.26%, 6.85%, and 0.91%, respectively. Pathologically confirmed breast cancer was revealed in 364 women giving the detection rate 4.59 for 1000. Cancer detection rate to expected incidence ratio was 3.35., Conclusions: Mammography service performed during the first year of breast cancer screening programme in the region of Lower Silesia conforms to quality assessment parameters recommended by the European guidelines at the acceptable level. The main problem at the start of this programme is too low coverage. Invitation process must be strongly intensified to improve long-term effectiveness and to significantly reduce breast cancer mortality.

Contents of estrogen receptors (ER) and progesterone receptors (PgR) in cells of breast cancers represent strong predictive factors. The higher is the contents of ER and PgR in breast cancer, the higher is a probability of obtaining a response to hormonal therapy and prognosis for the patient is better. In a routine manner, all tumours of mammary gland are subjected to evaluation of ER and PgR expression using immunohistochemistry. Forty ductal breast cancers (pT2N0) were subjected to an immunohistochemical evaluation (IHC) aimed at detection of ER and PgR expression. From every tumour three samples were taken for immunohistochemical studies: the lateral one from the side of axilla (ER-1; PgR-1); the median one (ER-2; PgR-2) and the medial one from the side of sternum (ER-3; PgR-3). The levels of both ER and PgR expression proved to be highly differentiated between the medial zone of the tumour and its periphery. The distinct expression of ER and PgR in ductal breast cancers, dependent on evaluated zone of the tumour, confirms its heterogeneous character and exerts an effect on the type of applied treatment.

Nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) is a 27 kDa chromosomal protein of unknown function. Its amino acid composition as well as the structure of its DNA binding domain resembles that of high mobility group A (HMGA) proteins, chromosomal proteins known as modulators of chromatin conformation and regulators of transcription. Conformation and function of the HMGA proteins are regulated by phosphorylation and acetylation. So far 19 phosphorylation sites had been reported in NUCKS. In this study, we have identified all known and six additional phosphorylation sites, and also mapped multiple sites of acetylation, methylation and formylation. We measured cell cycle dependent changes of phosphorylation and acetylation of NUCKS in HeLa cells through stable isotope labeling by amino acids in cell culture (SILAC), using the dephosphorylated protein for normalization. We identified sites that were highly phosphorylated or dephosphorylated in mitotically arrested cells as well as sites that were constitutively phosphorylated. The extent of acetylation is reduced in mitotically and G1 arrested cells. Analysis of human cancer specimens revealed that in tissues the extent of acetylation, formylation and methylation is higher than in cultured cells. In breast cancer samples, seven acetylation, three methylation, and three formylation sites were mapped in NUCKS. Of the 243 amino acids, at least 36 can be modified with a total of 57 posttranslational modifications. Thus, NUCKS appears to have the highest ratio of modified to unmodified residues of any protein so far described.

Background: The primary method of treatment of non-small cell lung cancer (NSCLC) in stage IIIB and IV is chemotherapy. Previous data suggested a correlation between cyclooxygenase-2 (COX-2) expression and the multidrug-resistant phenotype of cancer cells., Materials and Methods: In this prospective study, 32 patients with NSCLC in stage IIIB and IV from 1,078 patients were included. The expression of COX-2 as well as the expression of the ABC transporters MDR1/P-glycoprotein (MDR1/P-gp), BCRP and MRP1 were detected immunohistochemically., Results: Univariate and multivariate analyses demonstrated no prognostic or predictive significance of these proteins. It was merely demonstrated that complete or partial response are favourable factors for prediction of longer progression-free survival time. However, a strong positive correlation between the expression of COX-2, MDR1/P-gp and BCRP was found in NSCLC., Conclusion: These data suggest no clinical impact for the expression of MDR1/P-gp, MRP1, BCRP or COX-2 in NSCLC, but a putative coregulation of COX-2 and MDRI/P-gp and BCRP in NSCLC.

Unlabelled: Cancer of the rectum is an important problem for public health in Poland due to increasing incidence rate and still not satisfying treatment outcomes. Surgical management remains the mainstay of therapy. Because of introduction of the total mesorectal excision technique (TME) better locoregional control can be achieved. The value of the treatment method for clinical practice is associated with oncological effectiveness but it is also related to the risk of mortality and morbidity., The Aim of This Study: To assess the risk of mortality and morbidity of the curative anterior resection with TME in male patients and to evaluate the association between the incidence of postoperative complications and patient-, tumour- and treatment-related variables., Material and Methods: Consecutive 65 patients with histologically confirmed rectal cancer operated on with sphincter-saving TME method were studied prospectively RO resection was achieved in all cases. All anastomoses were constructed with end to end double-stapling technique. Adjuvant therapy was administered for 54% patients (in stages UICC II i III). 19% of patients received preoperative radiation with high-dose fractions to 25 Gy (5 x 5 Gy) and postoperative chemotherapy with 5-fluorouracil and leucovorin in six courses. In 35% of patients combined adjuvant radiotherapy to the total dose 50.4 Gy and chemotherapy scheduled as above was used., Results: There was no postoperative mortality. Early complications were noticed in 23% of patients: in 9.2% prolonged wound healing caused by superficial infection, in 6.9% anastomosis leakage (surgical treatment was performed in one patient), in 4.6% prolonged bowel paralysis, in 2.3% acute postoperative bleeding requiring relaparotomy. Late complications occurred in 16% of patients: in 6.9% anterior resection syndrome with bowel dysfunction (in one case defunctioning stoma was constructed), in 4.6% bladder dysfunction (nycturia with dysuria and urinary incontinence in 2.3% each), in 2.3% moderate benign anastomosis stricture and also in 2.3% complete sexual impotence. In patients with postoperative complications following factors were present: older age (> 75 years), obesity (BMI > 30), diabetes, preoperative radiotherapy and ultra low site of tumour (< 6 cm from the anal verge)., Conclusions: Anterior resection with TME technique is a safe procedure in male patients. The incidence of early and late postoperative complications seems to be acceptable especially considering the oncological advantages of this method. The risk of morbidity increases in older patients with obesity, diabetes, ultra low-sited tumours and after preoperative radiation therapy

Elevated metallothionein (MT) expression in ovarian cancers treated with cisplatin-based schemes represents an unfavorable prognostic index. MT expression is significantly higher in tumor samples obtained after chemotherapy. The present study aimed at examining MT expression in ovarian carcinoma cells sensitive (A2780) or resistant (A2780RCIS) against platinum drug treatment as well as examining effects of exposure to cisplatin on MT expression. Subcellular expression of MT was evaluated also in samples originating from 73 ovarian tumors. Cisplatin-resistant A2780RCIS cells were exposed to increasing cisplatin concentrations, and the subcellular expression of MT was determined by immunocytochemistry. The studies demonstrated that cisplatin-resistant A2780RCIS cells exposed to cisplatin typically manifested a nuclear MT expression. The study demonstrated also that exposure to cisplatin was paralleled by growing MT expression in cell nuclei. The nuclear expression of MT was also found to be specific for ovarian cancers of poor clinical outcome. No relationship could be demonstrated between cytoplasmic expression of MT and clinical variables. Nuclear MT expression is induced by cisplatin and seems to protect DNA in the cells from toxic effects of the drug.

The aim of study was the analysis of the association between AB0 and Rh blood groups and the prevalence of gallstone disease. 3156 patients (1654 women and 1472 men) from II Department of Internal Diseases of Medical University of Silesia were studied. This study did not reveal significant statistical correlation between the distribution of the AB0 and Rh blood groups and the prevalence of gallstone disease.

It is suggested that tumour stromal myofibroblasts exert an unfavourable effect on the biology of breast cancer. We are aware of only a single study which examined relationships between manifestation of myofibroblasts in the stroma of breast cancer and clinicopathological data of the patients. The present study was aimed at estimation of the effect exerted by myofibroblasts present in the tumour stroma on principal pathological parameters and on expression of Ki67, P53 and HER-2 proteins in the group of the most frequent breast cancers, the ductal cancers. In paraffin sections of 60 ductal breast cancers (20 cases in G1, 20 in G2 and 20 in G3), immunohistochemical reactions were performed to detect expression of smooth muscle actin (SMA) in order to visualize myofibroblasts, Ki67, P53 and HER-2. The studies demonstrated that the most numerous myofibroblasts were present in G3 cases and they were the least frequent in G1 cases (P = 0.02). Positive correlations were observed between the presence of myofibroblasts in tumour stroma and expression of Ki67 and HER-2 in breast cancer cells in the entire group (P < 0.001 and P = 0.001, respectively), in G2 cases (P = 0.003 and P = 0.03) and in G3 cases (P = 0.01 and P = 0.03). Considering that the higher grade, Ki67 and HER-2 are thought to represent unfavourable prognostic factors, the elevated content of myofibroblasts in tumour stroma is probably typical for cases with worse prognosis.

Background. The choice of treatment method for metastases to the spine remains an unresolved and controversial question. The major complication in disseminated neoplastic disease compression of the spine and nervous elements. Vertebroplasty performed jointly with palliative radiotherapy has been proposed as a procedure to treat metastases complicated by cancer infiltrations in the vicinity of the spine. Material and methods. We examined 21 patients treated since May 2004. Vertebroplasty was performed by surgery using acrylic cement, followed by palliative radiotherapy. Results. Outcome was assessed by clinical examination, neurological evaluation, and other methods, such as X-ray, CT scan, and MRI. All patients showed prompt relief of pain and substantial improvement in mobility. No complications or side effects were observed in connection with the joint palliative treatment. Conclusions. Vertebroplasty is an effective method and works to help stabilize spinal fractures. Satisfactory results were obtained using palliative treatment. The use of acrylic cement made it possible to perform radiotherapy safely with an optimum margin of healthy tissues, which enhances treatment. These initial results point to the need for further clinical collaboration between neurosurgeon and radiotherapist.

In case of breast cancer the grade of differentiation and expression of oestrogen and progesterone receptors falls within the first category of prognostic factors according to the College of American Pathologists. HER-2, p53 and Ki67 belong to the second category and their significance still awaits confirmation. The aim of the present study was to examine the relationship between the intensity of expression of oestrogen receptors (ER), progesterone receptors (PgR), HER-2, p53 and Ki67 in cells of ductal breast cancer of G1, G2 or G3 differentiation grade. In paraffin sections of 60 ductal breast cancers (20 cases in G1, 20 in G2 and 20 in G3), immunocytochemical reactions were performed to detect the expression of ER, PgR, HER-2, p53 and Ki67. Following a semi-quantitative appraisal of the preparations under examination, appropriate statistical tests were used to document significant relationships. We noted significant positive correlations between ER and PgR (the entire group studied, G1-3, and the G1 group), HER-2 and p53 (G2) and between p53 and Ki67 expression (G2). Significant negative correlations were found between ER and p53 (G1-3), PgR and p53 (G1-3, G1, G3) and between PgR and Ki67 (G1-3, G2). The studies performed demonstrated distinct relationships between the expression intensity of various proteins in tumour cells in relation to the grade of differentiation of the tumour. We also showed that a parallel determination of ER, PgR and p53 expression may carry high predictive value as to response to tamoxifen treatment.

Unlabelled: The aim of this study was to assess the prognostic value of Jass and Dukes classification of rectal cancer., Material and Method: The impact of these staging systems on five-year disease-free survival has been estimated in univariate and multivariate analysis for the group of ninety-two curatively treated patients., Results: In univariate analysis a relationship between survival and stage of disease has been found with a high degree of statistical significance for both Jass (I: 89.3 +/- 5.9; II: 54.2 +/- 10.2, p< 0.005; III: 14.3 +/- 9.4, p< 0.001; IV: 12.0 +/- 6.5, p < 0.001) and Dukes (A: 88.1 +/- 6.4; B: 41.0 +/- .9, p < 0.001; C: 15.4 +/- 7.1, p < 0.001) classifications. Cox regression model has identified Jass system as the best predictor of prognosis (II: p < 0.05; III: p < 0.001; IV: p < 0.001) and has shown the lack of significance for Dukes classification. In multivariate analysis of specific pathological features constituting Jass scale a significant and independent influence on survival (p < 0.05) has been noticed for the depth of penetration through the bowel wall, type of tumour growth and lymphocytic infiltration but not for the number of positive lymph nodes., Conclusion: Jass classification of rectal cancer is a prognostically effective modification of Dukes system as the result of addition of histological parameters significantly affects the prognosis.

Objectives: Ki67 and PCNA proteins are characteristic for cells in mitotic cycle and represent unfavourable prognostic indices. Intensity of the proteins expression directly correlates with grade of tumour differentiation. They belong to the second category of prognostic factors in breast cancer according to the College of American Pathologists., Design: Present study aimed at examining the relationship between intensity of expression of proliferation-related antigens--Ki67 and PCNA in cells of ductal breast cancer of G1, G2 or G3 differentiation grade., Materials and Methods: In paraffin sections of 60 ductal breast cancers, immunocytochemical reactions were performed to detect expression of Ki67 and PCNA. Following semiquantitative appraisal of studied preparations, appropriate statistical tests were used to document statistical relationships., Results: Intensity of Ki67 expression was most pronounced in G3 group and least pronounced in G1 group (ANOVA rang Kruskal-Wallis, p=0.00001). In the case of PCNA we did not show any differences. Only in the G1 we showed a positive correlation between expression intensity of studied antigens (Spearmans rang correlation, r=0.67, p=0.024)., Conclusions: The study showed that Ki67 and not PCNA correlates with morphologic features of proliferation.

The aim of this study was to estimate the prognostic value of clinical and pathomorphological factors in cancer of the colon and rectum. We studied seventy-seven patients subjected to a radical surgery with a five-year follow-up. Survival was calculated using the Kaplan-Meier method and compared by log-rank test. Multivariate analysis was performed using Cox's regression model. Overall 5-year survival was 68%. Primary tumour spread beyond the bowel wall and regional lymph node involvement appeared to be independent prognostic factors, significantly influencing the survival of patients. Other variables including patient's age and sex, tumour location, symptom duration before treatment onset, grade of differentiation and mucinous histology had no significant impact on prognosis. Tumour spread beyond the bowel wall and metastases to regional lymph nodes are the most useful prognostic factors in patients with colorectal carcinoma. In routine practice the clinical stage of cancer should remain a reference against which other clinical and pathomorphological variables are assessed.