The -553 T/A polymorphism in the promoter region of the FGF2 gene is associated with increased breast cancer risk in Polish women.

INTRODUCTION: Fibroblast growth factor-2 (FGF2) is an important signalling molecule contributing to angiogenesis, tumour growth and progression and its expression is implicated in breast cancer (BC) development. We investigated whether -553 T/A FGF2 gene polymorphism is associated with the risk and progression of BC in Polish women. MATERIAL AND METHODS: The -553 T/A polymorphism was genotyped in 230 breast cancer patients and 245 control subjects, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. Moreover, FastQuant human angiogenesis array was used to measure FGF2 levels in tumour (n = 127) and serum (n = 76) samples. RESULTS: The T/A genotypes (OR = 2.12, 95% CI: 1.20-3.74) (p = 0.08) and the combined heterozygotes T/A and homozygote A/A (OR = 2.18, 95% CI: 1.24-3.83) (p = 0.006) had an increased risk of BC. The median FGF2 levels in the tumours of A allele carriers were significantly increased compared to T/T patients, whereas in serum FGF2 levels were hardly altered among different genotype carriers. Significantly higher frequency of A allele was found in patients with lymph node metastases (OR = 2.53; 95% CI: 1.23-5.17) (p = 0.009) and human epidermal growth factor receptor 2 positive tumour (OR = 3.22, 95% CI: 1.49-6.99) (p = 0.002). Furthermore, Kaplan-Meier survival analysis showed that the A allele predicted worse disease-free survival (DFS) in BC patients. CONCLUSIONS: Our study shows for the first time that the -553 T/A FGF2 gene polymorphism may be associated with a risk of BC developing and progression in Polish women and may have prognostic value for the assessment of BC high-risk groups.

Prediction of survival for patients with advanced colorectal cancer using (1) H High-resolution magic angle spinning nuclear MR spectroscopy.

PURPOSE: To evaluate whether the metabolic profiles of colorectal cancer specimens can be used for prediction of survival. MATERIALS AND METHODS: The metabolic profiles of colorectal cancer tissues were determined using the high-resolution magic angle spinning (HR MAS) nuclear magnetic resonance (NMR) technique (16.4 T). HR MAS analysis was performed for 52 tissues taken from patients classified as survivors and nonsurvivors (30). Quantitative analysis was performed for each spectrum. Receiver operating characteristic (ROC) curves were used to evaluate the potential to predict patient survival over 5.5 years. RESULTS: Analysis of (1) H NMR spectra led to the identification and quantitative analysis of 30 metabolites. A significant increase in the Tau/Gly and Tau/MI ratios were associated with long-term survival (P = 0.004 and P = 0.003, respectively). ROC analysis indicated that the Tau/MI ratio had the best predictive value for survival (sensitivity 64.7% and specificity 100%). Good predictive value of survival was found for Tau/Gly ratio (sensitivity 63.6% and specificity 96.3%). Moreover, the Glu/Gln metabolic ratio with a cutoff level of 1.74 was predictive of survival with a sensitivity of 83.3% and a specificity of 85.7%. CONCLUSION: Our results indicate that HR MAS spectroscopy is potentially useful for survival prediction in advanced colorectal cancer.

[The value of Ki-67 antigen expression in tissue microarray method in prediction prognosis of patients with endometrioid endometrial cancer]. / Znaczenie ekspresji antygenu Ki-67 ocenianej metoda mikromacierzy tkankowych dla rokowania u chorych z gruczolakorakiem endometrialnym endometrium.

OBJECTIVES: To assess the prognostic significance of Ki-67 expression in the tissue microarray method (TMA) for disease free survival (DFS) and overall survival (OS) in endometrioid endometrial cancer (EEC). MATERIAL AND METHODS: The study examined 159 consecutive patients aged 37-86 (62.82 +/- 9.95) with EEC stages I-III according to FIGO, treated surgically at the Pirogow Memorial Hospital of Lodz between 2000 and 2007. Afterwards they were subsequently treated and examined at the Regional Cancer Center Copernicus Memorial Hospital of Lodz. Tissue cores 2 mm in size, in duplicate, were taken from the formalin-fixed and paraffin-embedded tissue donor blocks from surgery and constructed into the TMA recipient blocks. Using TMA method, the relationship between Ki-67 expression, DFS and OS was examined. DFS was defined as a period from primary surgery until relapse. OS was defined as a period from primary surgery until the end of the follow-up (60 months) or until the death of the patient. The study was approved by the Ethics Committee of the Medical University of Lodz (RNN/82/11/KE; KE/1673/12). RESULTS: The follow-up time varied between 3-60 months (51.42 +/- 15.87). In 31 patients (19.50%) the relapse of was diagnosed 1-59 months (24.97 +/- 16.08) after commencement of the treatment. During follow-up 32 patients (20.12%) died. DFS and OS were 80.50% and 79.88%, respectively The lack of Ki-67 expression was found in 37 cases (23.27%) while in 122 patients (76.73%) the expression was present (p < 0.001). The expression of Ki-67 in 1-10%, 11-20% and > 20% was present in 76 cases, 26 cases and 20 cases, respectively Positive correlation between the expression of Ki-67 and staging was present (r = 0.353; p < 0.001). In EEC patients with no relapse diagnosed during follow-up the expression of Ki-67 was present in 7.63 +/- 7.57% of EEC cells, when compared to 23.06 +/- 22.93% in EEC patients in relapsed disease (p < 0.001). The relationship between increased Ki-67 expression and increased grading was not statistically significant (r = 0.149; p = 0.061). The expression of Ki-67 did not depend on patient age (r = 0.040; p = 0.617). In univariate analysis negative correlation was found between the expression of Ki-67 and DFS (p < 0.001) and OS (p = 0.01). In multivariate analysis worse DFS was related to higher staging of EEC (p < 0.0 01) and increased expression of Ki-67 (p < 0.001). Worse OS was related to higher staging in multivariate analysis (p < 0.001). Ki-67 expression was not related to OS in multivariate analysis. Age of patients and grading of the EEC were not related to DFS and OS. CONCLUSIONS: The expression of the Ki-67 can significantly affect therapeutic decisions in selected EEC patients. The high Ki-67 expression in EEC patients is related to increased risk of relapse. The TMA technique is a good method for the assessment of the Ki-67 in studies conducted in EEC patients and makes it easier to carry out immunohistochemistry in large populations of patients.

[The value of progesterone and estrogen receptors expression in tissue microarray method in prognosis of patients with endometrioid endometrial cancer]. / Znaczenie ekspresji receptorów progesteronowych i estrogenowych ocenianej metoda mikromacierzy tkankowych dla rokowania u chorych z gruczolakorakiem endometrioidalnym endometrium.

OBJECTIVES: To assess prognostic significance of progesterone receptors (PR) and estrogen receptors (ER) expression in the tissue microarray (TMA) technique for disease free survival (DFS) and overall survival (OS) in endometrioid endometrial cancer (EEC). MATERIAL AND METHODS: The study included 151 consecutive patients, aged 37-86 years (62.80 +/- 9.99), with the EEC in stages I-III (FIGO), treated surgically at the Pirogow Memorial Hospital of Lodz between 2000 and 2007. Afterwards, they were subsequently treated and examined at the Regional Cancer Center, Copernicus Memorial Hospital of Lodz. Tissue cores 2 mm in size, in duplicate, were taken from the formalin-fixed and paraffin-embedded tissue donor blocks from surgery and constructed into the TMA recipient blocks. Using TMAs, the expression of PR and ER was examined and presented as Total Score (TS). The TS was determined by adding the intensity and marker distribution scores in a given case. The relationship between PR and ER expression, DFS and OS was examined. DFS was defined as the period from primary surgery until relapse. OS was defined as the period from primary surgery until the end of the follow-up (60 months) or until the death of the patient. The study was approved by the Ethics Committee of the Medical University of Lodz (RNN/82/11/KE). RESULTS: Lack of the PR and ER expression was found in 46 cases (30.46%) and 67 cases (44.37%), respectively. The expression of the PR and ER was weak in 24 cases (15.89%) and 22 cases (14.57%), respectively. Strong PR and ER expression was found in 81 patients (53.65%) and 62 patients (41.06%), respectively. Follow-up after surgery varied from 3 to 60 months (50.95 +/- 16.36). In 30 patients (19.87%) relapse was diagnosed 1-54 months (22.17 +/- 15.59) after surgery. During follow-ups, 29 patients (19.21%) died. In univariate analysis better DFS was related to the presence of PR (p = 0.010), higher TS of PR (HR = 0.81; 95% CI 0.71-0.94), the presence of ER (p = 0.001) and higher TS of ER (HR = 0.88; 95% CI 0.78-0.99). DFS differed significantly between the groups: without PR and ER expression (A), with presence of the PR but not ER expression (B), with the ER but not PR expression (C) and with the PR and ER expression (D) (p = 0.004). In univariate analysis OS was not related to PR expression (p = 0.110), TS of PR (HR = 0.89; 95% CI 0.80-1.02) and ER expression (p = 0.070). TS of ER was connected to better OS (HR = 0.83; 95% CI 0.72-0.96). The OS differed between groups A, B, C and D (p = 0.006). In multivariate analysis variants of PR/ER expression influenced the DFS (p = 0.039) and OS (p = 0.016). CONCLUSIONS: The expression of the PR and ER can significantly affect therapeutic decisions in selected patients with EEC. In EEC, common assessment of PR and ER expression is of higher prognostic value, than compared to single evaluation of PR and ER receptors.

Membrane expression of TRAIL receptors DR4, DR5, DcR1 and DcR2 in the normal endometrium, atypical endometrial hyperplasia and endometrioid adenocarcinoma: a tissue microarray study.

PURPOSE: To evaluate the membrane expression of DR4, DR5, DcR1 and DcR2 in the normal endometrium (NE), atypical endometrial hyperplasia (AEH) and endometrioid adenocarcinoma (EAC). METHODS: The study comprised 197 patients: 20 NE, 18 AEH and 159 EAC. Tissue microarrays were constructed. Membrane expression of DR4, DR5, DcR1 and DcR2 was examined and presented as total score (TS). RESULTS: In EAC, the membrane expression of DR4, DR5 and DcR2 was less common compared to NE (p < 0.001; p < 0.001; p = 0.018) and AEH (p < 0.001; p < 0.001; p = 0.004). In EAC the membrane expression of DcR1 did not differ when compared to NE (p = 0.055) and AEH (p = 0.173). A strong correlation was found between the type of endometrial tissue (NE/AEH/EAC) and the TS of DR4 (p < 0.001), DR5 (p < 0.001), DcR1 (p = 0.033) and DcR2 (p < 0.001). In EAC, the TS of DR4, DR5, DcR1 and DcR2 was not related to grading and staging. In EAC, the membrane expression of DR5, but not DR4, DcR1 and DcR2, was related to better disease-free survival (DFS). The overall survival (OS) was not related to membrane TRAIL receptors expression. CONCLUSIONS: The membrane expression of the receptors for TRAIL DR4, DR5, DcR1 and DcR2 is greater in NE than EAC. The level of membrane staining of the receptors in EAC is not dependent on grading and staging. In EAC patients, membrane expression of DR4, DR5, DcR1 and DcR2 are not independent predictors of survival.

[Effectiveness of tissue microarray technique for the assessment of estrogen and progesterone receptors expression in endometrioid endometrial cancer--preliminary report]. / Efektywnosc zastosowania techniki mikromacierzy tkankowych do oceny ekspresji receptorów estrogenowych i progesteronowych w gruczolakoraku endometrioidalnym endometrium--doniesienie wstepne.

OBJECTIVES: To assess the effectiveness of the donor-block biopsies with a 2 mm-size needle in endometrioid endometrial cancer (EEC) in the tissue microarray (TMA) technique and the application of the TMA for estrogen receptors (ER) and progesterone receptors (PR) expression in EEC. MATERIAL AND METHODS: The study examined EEC tissues from 60 patients. Tissue cores, 2 mm in size, in duplicate, were taken from the formalin-fixed and paraffin-embedded tissue donor blocks and constructed into the TMA recipient block. The presence of EEC tissue in the TMAs was analyzed, and the ER and PR expressions were examined. RESULTS: EEC tissue in TMAs was confirmed in 56 cases (93.33%). In 49 of them (81.67%), both cores presented with cancer tissues. In 4 cases (6.67%) EEC tissue was absent. All cases with ECC present on the TMA slides were appropriate for the ER and PR analysis. In 29 EEC cases (51.98%) both ER and PR were expressed. In 3 cases (5.36%) only ER was expressed, in 8 cases (14.29%) only PR was expressed, and in 16 cases (28.57%) ER and PR were assessed as negative. CONCLUSIONS: Two 2 mm-sized tissue cores from donor-block biopsies constructed into the TMA recipient block were sufficient to diagnose EEC and enabled the assessment of ER and PR expression in 93.3% of the cases. The use of the described TMA technique makes the immunohistochemical study of EEC easier and more time-efficient.

Comparison of prognosis in patients with endometrioid endometrial cancer staged IB in FIGO 1988 and 2009 classifications.

PURPOSE: Since 2009 the new FIGO Staging System of endometrial cancer, which changed the previous FIGO 1988 Staging System, has been in use. The aim of the study was to compare prognosis in patients with endometrioid endometrial cancer at stage IB of the 2009 FIGO Staging System and of the 1988 FIGO Staging System. METHODS: We analyzed 173 patients: 108 patients (group A) at stage IB in FIGO 1988 Staging System, and 68 patients (group B) at stage IB in FIGO 2009 Staging System from 262 consecutive endometrioid endometrial cancer patients. The disease-free survival (DFS) and overall survival (OS) were compared between these groups. RESULTS: The DFS rate was 96.3 % in group A and it was 87.7 % in group B (p = 0.029). Relapses were observed in 12 patients (6.4 %) from 6 to 57 months (mean 28.1; SD = 14.6) after initial surgery, and occurred in four patients from group A (3.7 %) and eight patients from group B (12.3 %) (p = 0.032). The OS rate was 94.4 % in group A and it was 83.1 % in group B (p = 0.018). During follow-up, 17 patients (9.8 %) died: six patients from group A (5.6 %), and 11 patients from group B (16.9 %). CONCLUSIONS: Stage IB in FIGO 2009 Staging System is associated with worse prognosis compared to stage IB according to FIGO 1988 classification. There seems to be a need to use exclusively the new FIGO 2009 classification worldwide to avoid therapeutic mistakes, which can be caused by diverse nomenclature.

Angiogenesis markers quantification in breast cancer and their correlation with clinicopathological prognostic variables.

Tumoural angiogenesis is essential for the growth and spread of breast cancer cells. Therefore the aim of this study was to assess the diagnostic performance of angiogenesis markers in tumours and there reflecting levels in serum of breast cancer patients. Angiogenin, Ang2, fibroblast growth factor basic, intercellular adhesion molecule (ICAM)-1, keratinocyte growth factor (KGF), platelet-derived growth factor-BB, and VEGF-A were measured using a FASTQuant angiogenic growth factor multiplex protein assay. We observed that breast cancer tumours exhibited high levels of PDGF-BB, bFGF and VEGF, and extremely high levels of TIMP-1 and Ang-2, whereas in serum we found significantly higher levels of Ang-2, PDGF-BB, bFGF, ICAM-1 and VEGF in patients with breast cancer compared to the benign breast diseases patients. Moreover, some of these angiogenesis markers evaluated in tumour and serum of breast cancer patients exhibited association with standard clinical parameters, ER status as well as MVD of tumours. Angiogenesis markers play important roles in tumour growth, invasion and metastasis. Our results suggest that analysis of angiogenesis markers in tumour and serum of breast cancer patients using multiplex protein assay can improve diagnosis and prognosis in this diseases.

WWOX expression in colorectal cancer--a real-time quantitative RT-PCR study.

The WWOX gene is a tumour suppressor gene affected in various types of malignancies. Numerous studies showed either loss or reduction of the WWOX expression in variety of tumours, including breast, ovary, liver, stomach and pancreas. Recent study demonstrated that breast cancer patients exhibiting higher WWOX expression showed significantly longer disease-free survival in contrast to the group with lower relative WWOX level. This work was undertaken to show whether similar phenomena take place in colon tumours and cell lines. To assess the correlation of WWOX gene expression with prognosis and cancer recurrence in 99 colorectal cancer patients, we performed qRT-PCR analysis. We also performed analysis of WWOX promoter methylation status using MethylScreen method and analysis of loss of heterozygosity (LOH) status at two WWOX-related loci, previously shown to be frequently deleted in various types of tumours. A significantly better disease-free survival was observed among patients with tumours exhibiting high level of WWOX (hazard ratio = 0.39; p = 0.0452; Mantel-Cox log-rank test), but in multivariate analysis it was not an independent prognostic factor. We also found that although in colorectal cancer WWOX expression varies among patients and correlates with DFS, the exact mode of decrease in this type of tumour was not found. We failed to find the evidence of LOH in WWOX region, or hypermethylation in promoter regions of this gene. Although we provide the evidence for tumour-suppressive role of WWOX gene expression in colon, we were unable to identify the molecular mechanism responsible for this.

[Endometrioid endometrial cancer--the prognostic value of selected clinical and pathological parameters]. / Gruczolakorak endometrium typu endometrioidalnego--analiza wartosci prognostycznej wybranych parametrów klinicznych i histopatologicznych.

OBJECTIVES: To assess the relationship between selected clinical and pathological factors and disease free survival (DFS) and overall survival (OS) in endometrioid endometrial cancer patients. MATERIAL AND METHODS: A retrospective review of 262 patients aged 37-86 (6.0 +/- 9.0) was performed. Selected clinical and pathological data were correlated with DFS and OS. RESULTS: Follow-up was 8-123 months (64.9 +/- 27.1). In 4 patients (1.5%) clinical progression was diagnosed during the treatment. In 43 patients (16.4%) relapse was diagnosed 2-61 months (23.9 +/- 15.7) after commencing treatment. DFS and OS were 82.1% and 81.3% respectively. In univariate analysis worse DFS was related to older patients (p = 0.007) and non-radical surgery (p < 0.001). In multivariate analysis worse DFS was related to older patients (HR = 1.058; 95% CI = 1.024-1.093; p < 0.001), younger at menopause (HR = 0.910; 95% CI = 0.851-0.973; p = 0.006), with higher staging (HR = 2.639; 95% CI = 1.968-3.539; p < 0.001) operated non-radically (HR = 0.220; 95% CI = 0.096-0.504; p < 0.001). In univariate analysis worse OS was connected with older patients (p = 0.018), diabetes type II (p = 0.019) and non-radical surgery (p < 0.001). In multivariate analysis worse OS was related to younger age at menopause (HR = 0.932; 95% CI = 0.873-0.996; p = 0.039), diabetes type II (HR = 2.372; 95% CI = 1.260-4.466; p = 0.008), higher staging (HR = 2.053; 95% CI = 1.482-2.845; p < 0.001), and non-radical surgery (HR = 0.240; 95% CI = 0.091-0.636; p = 0.004). CONCLUSIONS: Relapsed endometrial cancer developed in 90.7% during four years after commencing treatment. In 79.1% of these patients distant metastases were present. Most significant prognostic factors were radicality of surgery age of patients and staging. The presence of diabetes type II and early menopause were connected with worse prognosis.

ABCB1/MDR1 gene polymorphisms as a prognostic factor in colorectal cancer.

OBJECTIVE: To analyse the single-nucleotide polymorphisms (SNPs): ABCB1(1236C>T), ABCB1(2677G>T/A), ABCB1(3435C>T) and haplotypes in the ABCB1/MDR1 gene, which could contribute to genetic risk of colorectal cancer (CRC). Disease association between the ABCB1/MDR1 genotype, allele, haplotype frequencies and histological features, such as TNM classification, localization of primary carcinoma, grade of malignancy, histological type of tumour, lymphoid infiltration and vessel invasion were estimated. In this study, the potential role of SNPs of the ABCB1/MDR1 gene as a prognostic marker for CRC was analysed. MATERIALS AND METHODS: Tumour specimens of 95 patients with CRC were studied. Using automated sequencing or PCR-RFLP method, DNA for three common SNPs of ABCB1/MDR1 was extracted and analysed. The results of genotyping and haplotype analysis with histopathological features, grading and clinical staging of neoplasms were correlated. RESULTS: A statistically significant higher frequency of T(1236) allele in T1/T2 (89.7%), M0 groups (81.6%) and I/II clinical staging (82.7%) in comparison with T3/T4 (68.2%), M1 groups (47.4%) and III/IV clinical staging (65.1%) was detected. Furthermore, multivariate analysis according to Cox's proportional hazard model indicated that the T(1236) allele is a good, independent prognostic factor and the presence of this allele decreases the risk of death in comparison with a group without this allele (HR = 0.26; p = 0.0424). In addition, a statistically significant higher frequency of C(3435) allele and significant differences in the C(3435) allele distribution in N1/N2 group (91.7% and 62.5%, respectively) than N0 group (71.2% and 44.9%, respectively) was found. Each of the eight possible haplotypes was noted in M0 or I/II group and only seven in M1 or III/IV group. Haplotype T(1236)-G(2677)-C(3435) only in less advanced CRC subjects (9.6% in I/II and 9.2% in M0 group) was detected. In addition, significant differences in haplotype distributions between M0 or I/II and M1 or III/IV group were found (p = 0.01 and p = 0.05, respectively). CONCLUSIONS: These results suggest association between T(1236) allele and T(1236)-G(2677)-C(3435) haplotype and less advanced CRC, so these genetic markers may play a role as potentially good prognostic factors. Differences in haplotype distributions and degree of clinical staging may suggest that some other potential SNPs, especially in regulatory region of ABCB1/MDR1 gene, may influence P-glycoprotein function and CRC progression.

TRAIL protein expression in breast cancer cells correlates with nuclear grade.

INTRODUCTION: TRAIL protein may serve as an escape mechanism for cancer cells from the immune response. The aim of the study was to assess whether the presence of TRAIL protein correlates with unfavourable prognostic factors in breast carcinoma. MATERIAL AND METHODS: The study group was composed of breast cancer patients treated surgically in the Department of Surgical Oncology, Medical University of Lodz, Poland, from January to December 2003. Inclusion criteria for the study were fulfilled by 117 women. The immunohistochemical study of TRAIL protein expression was performed in 118 breast carcinomas diagnosed in the study group. TRAIL protein expression was correlated with other variables: tumour size, lymph node status, grade, histological type of carcinoma, oestrogen and progesterone receptor status, HER2 expression, presence of lymphovascular invasion and age of the patient. RESULTS: Expression of TRAIL protein was present in 73% of breast carcinomas. The percentage of TRAIL-expressing breast carcinoma cells correlated with the nuclear grade (τ = 0.26, p < 0.05; Tau Kendall test). The intensity of TRAIL expression (intensity of staining) in breast carcinoma cells correlated with the nuclear grade (τ = 0.15, p < 0.05; Tau Kendall test). TRAIL expression in breast carcinoma did not correlate with other studied variables. CONCLUSIONS: Our analysis revealed that expression of TRAIL protein in breast carcinoma cells correlates with nuclear grade of carcinoma.

cDNA sequencing improves the detection of P53 missense mutations in colorectal cancer.

BACKGROUND: Recently published data showed discrepancies between P53 cDNA and DNA sequencing in glioblastomas. We hypothesised that similar discrepancies may be observed in other human cancers. METHODS: To this end, we analyzed 23 colorectal cancers for P53 mutations and gene expression using both DNA and cDNA sequencing, real-time PCR and immunohistochemistry. RESULTS: We found P53 gene mutations in 16 cases (15 missense and 1 nonsense). Two of the 15 cases with missense mutations showed alterations based only on cDNA, and not DNA sequencing. Moreover, in 6 of the 15 cases with a cDNA mutation those mutations were difficult to detect in the DNA sequencing, so the results of DNA analysis alone could be misinterpreted if the cDNA sequencing results had not also been available. In all those 15 cases, we observed a higher ratio of the mutated to the wild type template by cDNA analysis, but not by the DNA analysis. Interestingly, a similar overexpression of P53 mRNA was present in samples with and without P53 mutations. CONCLUSION: In terms of colorectal cancer, those discrepancies might be explained under three conditions: 1, overexpression of mutated P53 mRNA in cancer cells as compared with normal cells; 2, a higher content of cells without P53 mutation (normal cells and cells showing K-RAS and/or APC but not P53 mutation) in samples presenting P53 mutation; 3, heterozygous or hemizygous mutations of P53 gene. Additionally, for heterozygous mutations unknown mechanism(s) causing selective overproduction of mutated allele should also be considered. Our data offer new clues for studying discrepancy in P53 cDNA and DNA sequencing analysis.

ABCB1 gene polymorphisms and haplotype analysis in colorectal cancer.

PURPOSE: The aim of this study was to determine the significance of three most common single-nucleotide polymorphisms (SNPs) of ABCB1 gene in the development of colorectal cancer and to estimate the influence of these SNPs to surviving patients' treatment combination adjuvant therapy 5-fluorouracil/leucovorin. Haplotype structure of ABCB1 was analysed, and degree of linkage disequilibrium (LD) between SNPs of ABCB1 was estimated. MATERIALS AND METHODS: Tumour specimens of 95 patients with colorectal cancer and blood samples of 95 healthy cases were studied. Genotyping of ABCB1 gene was performed by automated sequencing or polymerase chain reaction-restriction fragment length polymorphism method. Comparison of frequencies of alleles/genotypes/haplotypes between the studied group (colorectal cancer samples) and the control group (blood samples) were analysed. These results were correlated with the surviving patients after treatment of adjuvant chemotherapy. RESULTS: Significant differences in ABCB1 (1236C>T) (p = 0.00043) and ABCB1 (2677G>T/A) (p = 0.04) genotype distribution and T(1236) allele distribution (CT(1236) or TT(1236) vs CC(1236); p = 0.0499, OR = 0.55, Fi-Yule coefficient = 0.14) were found. A strong LD between ABCB1 (1236C>T) and ABCB1 (2677G>T/A) SNPs (D' = 0.621, r (2) = 0.318) was detected. All SNPs were located in one haplotype block. There were significant differences in haplotype distributions between colorectal cancer patients and healthy population (p = 0.03). Significant differences in survival probability of colorectal cancer patients' treatment chemotherapy according to allele of ABCB1 (3435C>T) was observed. Survival probability of patients with wild-type C(3435) allele were higher than among patients without this allele (p = 0.04572). CONCLUSIONS: These results suggested that three studied SNPs of ABCB1 were located in one haplotype block. Differences in ABCB1 (1236C>T) and ABCB1 (2677G>T/A) genotypes and T(1236) allele distribution between investigated populations indicate significant impact of these SNPs on risk of development of colorectal cancer. Polymorphism ABCB1 (3435C>T) may be a prediction marker of cancer chemotherapy effectiveness. Differences in haplotype distributions between colorectal cancer patients and healthy population suggested that other potential SNPs, especially in regulatory region of ABCB1 gene, may influence P-glycoprotein expression and function.

Prognostic relevance of cyclin E expression in operable breast cancer.

BACKGROUND: Cyclin E is an important regulator of cell-cycle progression. High levels of cyclin E protein in breast cancer have been reported in association with higher disease stage, poor histological differentiation of tumor, and lack of steroid receptors. Data concerning the prognostic relevance of cyclin E expression in breast cancer are conflicting. The aim of this retrospective study was to evaluate the prognostic relevance of cyclin E expression assessed by immunohistochemistry in patients with operable invasive ductal breast cancer. MATERIAL/METHODS: The expression of cyclin E was analyzed by immunostaining in 174 women with breast cancer after radical mastectomy with a median follow-up period of 58 months. Tumor samples were judged to be negative (<2%) or positive (> or =2%) according to the percentage of cells showing the nuclear staining pattern. Ninety-nine (56.9%) tumor samples were regarded as cyclin E-positive. RESULTS: Positive staining for cyclin E determined poor prognosis compared with cyclin E-negative patients in all cases (five-year cancer-specific survival rate of 64.5 vs. 84.5%, p=0.005), in the node-positive group (50.9 vs. 82.1%, p=0.008), and in patients treated with adjuvant chemotherapy (71.0 vs. 96.6%, p=0.008). In a multivariate analysis, high expression of cyclin E was associated with a higher risk of death in the node-positive group (hazard ratio: 3.2, 95%CI: 1.3-8.2, p=0.015). CONCLUSIONS: It was demonstrated that a high expression of cyclin E measured by immunohistochemistry was a significant factor of poor prognosis, especially in the node-positive group.

[Abdominal Burkitt lymphoma mimicking the ovarian cancer. Case report and review of the literature]. / Postac brzuszna chloniaka Burkitta o obrazie klinicznym raka jajnika. Opis przypadku i przeglad pismiennictwa.

UNLABELLED: Primary Burkitt lymphoma is a lymphoblastic B-cell malignant tumor with very aggressive course. Its abdominal form involving internal genital organs is very rare. CASE: We report the case of 27-year-old woman treated for abdominal Burkitt lymphoma. The patient presented bilateral ovarian tumors with ascites, pain and elevated CA 125 over 900 IU/ml. During laparotomy an advanced neoplasmatic disease involving internal genital organs has been diagnosed. Bilateral salphingo-oophorectomy and omentectomy have been performed. Additionally, the neoplasmatic tumor from ileo-coecal region has been ressected in order to prevent ileus. Pathologic examination has revealed an abdominal Burkitt lymphoma. After surgery, polychemotherapy has been administered (COP followed by CODOX-M+IVAC). The patient, 36 months after surgical treatment, remains under the control of our Department. No signs of recurrence have been detected so far. CONCLUSIONS: The presence of primary abdominal Burkitt lymphoma may include clinical and laboratory findings suggesting the presence of ovarian cancer. Chemotherapy appears to be an essential therapeutic management for all forms of Burkitt lymphoma. Clinically advanced Burkitt lymphoma may be successfully managed with chemotherapy.

94% accuracy of intraoperative imprint touch cytology of sentinel nodes in skin melanoma patients.

UNLABELLED: The aim of the present study was to assess whether the reliability of imprint touch cytology (ITC) of sentinel nodes in skin melanoma patients allows intraoperative decisions regarding simultaneous radical lymphadenectomy to be made. PATIENTS AND METHODS: The results of ITC of sentinel nodes were compared with the results of standard histopathological and immunohistochemical examinations. RESULTS: A total of 148 sentinel nodes were identified in 98 lymph node groups in 85 skin melanoma patients. ITC revealed the presence of metastases in 7 out of 16 melanoma-positive sentinel nodes (sensitivity, 43.7%). There were no false-positive results of ITC of sentinel nodes (specificity, 100%). The negative predictive value of ITC was 93.6%, the positive predictive value was 100%, and the accuracy of the method was 93.9%. CONCLUSION: ITC of sentinel nodes is a reliable method. There was no risk of overtreatment due to false-positive results of sentinel node ITC in our study. High accuracy of the method warrants its clinical use.

Recurrence of cholangiogenous carcinoma in port-sites two years after laparoscopic removal of noncancerous gallbladder.

We present a unique case of carcinoma diagnosed in port-site, two years after uncomplicated laparoscopic cholecystectomy for benign cholecystitis. Analysis of morphology and cytokeratin profile (CK19+ and CK20+/-) of resected port-site tumor allows us to establish the diagnosis of tubular carcinoma with probable cholangiogenic origin. The primary carcinoma was not diagnosed in archival gallbladder tissue, despite repeated histological examination. No other primary tumor was identified during follow-up. Patient history and histological/immunohistochemical picture of the recurrent tumor suggested that primary carcinoma was probably located in the gallbladder, but was not detected during initial and repeated histological examinations of postoperative specimen. The patient is still alive, 12 months after the first port-site recurrence and 36 months after initial laparoscopy.