Wojciech Kielan

HER-2 Expression in Immunohistochemistry Has No Prognostic Significance in Gastric Cancer Patients

The role of HER-2 expression as a prognostic factor in gastric cancer (GC) is still controversial. The aim of the study was to asses HER-2 status, its correlations with clinicopathological parameters, and prognostic impact in GC patients. Tumor samples were collected from 78 patients who had undergone curative surgery. In order to evaluate the intensity of immunohistochemical (IHC) reactions two scales were applied: the immunoreactive score according to Remmele modified by the authors and standardised Hercep test score modified for GC by Hofmann et al. The HER-2 overexpression was detected by IHC in 23 (29.5%) tumors in Hercep test (score 2+/3+) and in 24 (30.7%) in IRS scale (IRS 4–12). The overexpression of HER-2 was associated with poorly differentiated tumors, but this correlation was not significant (P = 0.064). No relationship was found between HER-2 expression and primary tumor size and degree of spread to regional lymph nodes. Both univariate and multivariate analyses revealed that TNM stage and patients age were the crucial negative prognostic factors. No correlation was observed between patient survival and expression of HER-2 estimated using both scales. This research did not confirm HER-2 expression (evaluated with immunohistochemistry) value as a prognostic tool in GC.

Detection of viral DNA sequences in sporadic colorectal cancers in relation to CpG island methylation and methylator phenotype

There is evidence that insertion of viral DNA into a mammalian genome can lead to alterations of methylation patterns. The aim of the present study was to examine the presence of DNA sequences of five human DNA viruses (assessed by PCR): JC polyoma virus (JCV), human adenovirus (AdV), Epstein–Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV/HHV8) and human papillomavirus (HPV) in a cohort of 186 sporadic colorectal cancers (CRCs) and related these data with the methylation status of six CpG island methylator phenotype (CIMP)-specific genes (MLH1, CACNA1G, NEUROG1, IGF2, SOCS1, RUNX3) and seven cancer-related genes markers (p16, MINT1, MINT2, MINT31, EN1, SCTR and INHBB) assessed by methylation-specific PCR in 186 and 134 CRC cases, respectively. The AdV, KSHV and HPV were detected in four (2%), two (1%) and zero CRC cases, respectively, and thus were excluded from further analyses. Although 19% and 9% of the CRCs were positive for EBV and JCV, respectively, no associations between virus presence and CpG island methylation were found after correction for multiple testing. Our results demonstrate that the presence of DNA sequences of JCV and EBV in CRC is unrelated to the methylation of the 13 cancer-related CpG islands and CIMP.

Evaluation of changes in the activity of proteolytic enzymes and their inhibitors in the processes that accompany the growth of gastric cancer

BackgroundMany investigators have observed a correlation between the aggressiveness of malignant tumor growth and the levels of cysteine peptidases and their autogenous inhibitors. Cathepsins B and L are activated by pepsin in an acidic pH. This fact encouraged us to measure the activity of these enzymes in tissue samples of gastric cancer.MethodsWe measured the activities of cathepsins B and L, and their precursors and inhibitors, in homogenates of tissue samples obtained from operations for gastric cancer. We compared the results for the homogenates of tissues from three different sites: the tumor center, the zone of cancer invasion (border of the tumor), and healthy tissue.ResultsThe highest activities of free cysteine peptidases and those in complexes with their inhibitors, as well as their precursors, were observed in the border of the tumor, while the activities in healthy tissue were significantly lower.ConclusionThe local activities of cysteine peptidases and their inhibitors reflect the topographical differences between the center of the tumor, the zone of invasion, and healthy tissues in gastric cancer patients. In addition, the results for the pattern of changes in the activity of cysteine peptidases according to the degree of tissue infiltration were not dependent on the method of measurement (colorimetry vs spectrofluorometry).

The importance of preoperative elevated serum levels of CEA and CA15-3 in patients with breast cancer in predicting its histological type

It is not known whether in patients with breast cancer the occurrence of elevated serum tumour markers depends on its histological type. The aim of the study was to assess relationship between breast cancer histological type and the presence of increased serum levels of CEA and CA 15-3. The study population was 428 patients (all women, mean age 52.5 years), treated at The Department of Surgery of Wroclaw Medical University from 2005 to 2008 due to breast cancer. All of them had their preoperative CA 15-3 and CEA serum concentrations measured. According to the TNM system, 21% of patients were in stage I, 32.5% in stage II, 46.5% in stage III of the disease. In patients with ductal type of the cancer the elevated serum levels of CEA and CA 15-3 were observed in 48.7% and 42.2%, in lobular type in 42.4% and 52.5%, and in non-ductal/tubular types in 48.1% and 40.4% (p=N/S). Stepwise logistic regression analyses showed that ductal breast cancer is related to elevated CEA and normal CA 15-3 serum levels. The histological types of breast cancer are not significantly related to elevated serum levels of CEA and/or CA 15-3.

Cysteine peptidase inhibitors and activator(s) in urine of patients with colorectal cancer.

The total activity of cysteine peptidase inhibitors and activator(s) was determined in the samples of urine received from colorectal cancer patients. Patients with peptic ulcer and healthy volunteers agreed to be a control group. The studies revealed a marked difference between the values of the determined parameters for the patients with colorectal cancer and those for the control group. Determination of cysteine peptidase inhibitors in patients urine is proposed as a new diagnostic procedure.

Assessment of chromosomal imbalances in CIMP-high and CIMP-low/CIMP-0 colorectal cancers.

Data presented in a number of recent studies have revealed a negative correlation between CpG island methylator phenotype (CIMP) and chromosomal instability (CIN) measured by a loss of heterozygosity (LOH) of selected loci, suggesting that CIN and CIMP represent two independent mechanisms in sporadic colorectal cancer (CRC) carcinogenesis. However, CIN is a heterogeneous phenomenon, which may be studied not only by employing LOH analysis but also by observing chromosomal imbalances (gains and deletions). The current study aimed to investigate the relationship between CIMP and chromosomal gains and deletions (assessed by comparative genomic hybridization) in a group of 20 CIMP-high and 79 CIMP-low/CIMP-0 CRCs. Our results revealed that the mean numbers of gains and of total chromosomal imbalances were significantly greater (p = 0.004 and p = 0.007, respectively) in the CIMP-low/CIMP-0 group compared to the CIMP-high group, while no significant difference was observed between the mean numbers of losses (p = 0.056). The analysis of copy number changes of 41 cancer-related genes by multiplex ligation-dependent probe amplification showed that CRK gene was exclusively deleted in CIMP-low/CIMP-0 tumors (p = 0.02). Given that chromosomal losses play an important role in tumor suppressor inactivation and chromosomal gains, in the activation of proto-oncogenes, we hypothesize that tumor suppressor inactivation plays similar roles in both CIMP-high and CIMP-low/CIMP-0 CRCs, while the predominance of chromosomal gains in CIMP-low/CIMP-0 tumors may suggest that the activation of proto-oncogenes is the underlying mechanism of CIMP-low/CIMP-0 CRC progression.

Prognostic value of CA 19-9 level in resectable pancreatic adenocarcinoma

The prognosis in patients with pancreatic cancer is poor and some authors describe it as a lethal disease. At the time of diagnosis only 14% of patients could be surgically treated and up to 30% of them die within 12 months. Therefore, further clinical investigations on preoperative patient qualification are needed. A total of 81 patients were included into the study. The CA 19-9 concentration was measured before surgery by an automated, commercially available enzyme immunoassay in Axsym analyzer (Abott Diagnostics Laboratory). A value of 37 U/ml was used as the upper limit of normal levels. Tumors were staged according to the Union Against Cancer (UICC) of 2004 and graded during the histological evaluation according to the G0-G4 scale. All patients were monitored every three month via outpatient clinic visits. In the case of missing visit we contacted the families to establish the cause. We assessed perioperative, 12 month, 2 year and 5 year survival. Twelve moth, 2 year and 5 year survival were assessed in the whole studied population and in the group of patients with the exception of these who died during the perioperative period. The total five year survival was 6%. The median time of survival was 467 days (range: 163 - 586 days). The perioperative period was survived by 91.4% patients, 12 months were survived by 71.6% patients, 2 years were survived by 35.8% patients, 5 years were survived by 6.2% patients. The serum Ca 19-9 level was above the normal limit in 80.5% patients. ROC curve analysis revealed that CA 19-9 level of more than 106 U/ml was linked to 2 year survival with 79.3% sensitivity and 74.5% specificity. Preoperative level of CA 19-9 below 106U/ml represents a predictive factor of 2- and 5-year survival, independent of other factors, such as lower size of the tumor, absence of metastases to lymph nodes, female gender of patients. After exclusion of the patients who died in the perioperative period, no relationship could have been disclosed between preoperative CA 19-9 levels and one year survival. The observation points to the chance that patients with higher levels of CA 19-9 harbour micrometastases, the development of which is sufficiently slow to allow for a one-year survival of the patients but which increase the risk of death after two and five years.

Polish Consensus Statement On The Protective Stoma

Department of General and Colorectal Surgery, Bielański Hospital in Warsaw1 Department of Rehabilitation, J. Piłsudski University of Physical Education in Warsaw2 Z Katedry i Kliniki Chirurgii Ogólnej, Endokrynologicznej i Onkologii Gastroenterologicznej Department of General and Endocrinological Surgery and Gastroenterological Oncology, Medical University in Poznań, H. Święcicki Teaching Hospital in Poznań3 Department of General and Colorectal Surgery, K. Marcinkowski Medical University in Poznań4 Department of General and Colorectal Surgery, Military Medical Academy University Teaching Hospital, Central Veterans’ Hospital in Łódź5 2nd Department of General, Gastroenterological and Gastrointestinal Tumour Surgery, Medical University in Lublin, Independent Public Teaching Hospital No 1 in Lublin6 Department of Oncological Surgery, Oncology Centre, M. Skłodowska-Curie Institute in Cracow7 Department of General and Colorectal Surgery and Multi-Organ Trauma with Surgical Nursing Unit, Silesian Medical University, Provincial Specialist Hospital No 5 in Sosnowiec8 3rd Department of General Surgery, Jagiellonian University Collegium Medicum in Cracow9 Department of General Surgery, Solec Hospital in Warsaw10 Department of General, Oncological and Gastrointestinal Surgery, Medical Centre of Postgraduate Education in Warsaw11 Department of Oncological Surgery, Gdańsk Centre of Oncology, Polish Red Cross Maritime Hospital in Gdańsk12 Department of General and Oncological Surgery, Pomeranian Medical University, Independent Public Teaching Hospital No 2 in Szczecin13 Department of General, Oncological and Endocrinological Surgery, Provincial Hospital Complex in Kielce14 Department of Oncological Surgery, Professor F. Łukaszczyk Oncological Centre in Bydgoszcz15 Department of General and Oncological Surgery, University Teaching Hospital in Wrocław16 Department of General, Oncological and Chest Surgery, Central Teaching Hospital of the Ministry of National Defence, Military Medical Institute in Warsaw17 Department of General, Gastroenterogical and Oncological Surgery, L. Rydygier Collegium Medicum in Bydgoszcz, L. Rydygier Provincial Complex Hospital in Toruń18 Department of Surgery, Military Institute of Aviation Medicine in Warsaw19 Department of General, Oncological and Vascular Surgery, Provincial Specialist Hospital in Słupsk20

Control of active B and L cathepsins in tissues of colorectal cancer using cystatins isolated from chicken egg proteins: in vitro studies

The activity of cysteine peptidases (cathepsins B and L) was estimated in homogenates of tissues sampled during surgery from 60 patients operated due to colorectal tumors. The results were compared to those obtained using tissues in which histopathology disclosed no tumorous cells, obtained from 20 patients of the same group, treated as a control. Activity of the enzymes was inhibited using cysteine peptidase inhibitors isolated from chicken egg proteins. Application of the inhibitors was found to inhibit activity of the enzymes which play a key role in tumor development. It is suggested that in future the inhibitors may provide a component of new generation drugs in the so-called inhibitor therapy.

Clinical validation of nuclear factor kappa B expression in invasive breast cancer

Breast cancer is the most commonly diagnosed cancer in Polish women. The expression of transcription nuclear factor kappa B, a key inducer of inflammatory response promoting carcinogenesis and cancer progression in breast cancer, is not well-established. We assessed the nuclear factor kappa B expression in a total of 119 invasive breast carcinomas and 25 healthy control samples and correlated this expression pattern with several clinical and pathologic parameters including histologic type and grade, tumor size, lymph node status, estrogen receptor status, and progesterone receptor status. The data used for the analysis were derived from medical records. An immunohistochemical analysis of nuclear factor kappa B, estrogen receptor, and progesterone receptor was carried out and evaluation of stainings was performed. The expression of nuclear factor kappa B was significantly higher than that in the corresponding healthy control samples. No statistical difference was demonstrated in nuclear factor kappa B expression in relation to age, menopausal status, lymph node status, tumor size and location, grade and histologic type of tumor, and hormonal status (estrogen receptor and progesterone receptor). Nuclear factor kappa B is significantly overexpressed in invasive breast cancer tissues. Although nuclear factor kappa B status does not correlate with clinicopathological findings, it might provide important additional information on prognosis and become a promising object for targeted therapy.