Primary pneumococcal peritonitis with a fulminant course.

INTRODUCTION: Primary peritonitis is an inflammation of the peritoneal cavity in the absence of a localized intra-abdominal source. It is included in the differential diagnosis of acute abdomen and can be potentially life-threatening. Pneumococci were a frequent pathogen causing primary peritonitis especially in the preantibiotic era. Nowadays, they act as an uncommon primary pathogen. Pneumococcal peritonitis in adults is more frequently seen in cases of liver cirrhosis with ascites and other pre-existing conditions. Primary pneumococcal peritonitis is uncommon in healthy individuals and therefore its diagnosis is difficult. Secondary peritonitis has to be excluded. CASE REPORT: A 36-year-old woman was admitted to our surgery department with symptoms of severe sepsis. She reported a sudden onset of diffuse abdominal pain and was eight weeks after delivery per vias naturales. A computed tomography scan of the abdomen with intravenous contrast has not demonstrated any pathology explaining the condition of our patient. Empiric anti-microbial therapy with broad-spectrum antibiotics was commenced and a laparotomy was performed, which also did not reveal any source of infection. Purulent odorless fluid was found in the peritoneal cavity. Peritoneal lavage with an antiseptic was performed. Cultures from peritoneal fluid demonstrated a monobacterial growth of Streptococcus pneumoniae. The condition of our patient improved after continued adequate antibiotic therapy and lavage. CONCLUSION: Primary pneumococcal peritonitis is difficult to diagnose in healthy individuals, since it is mimicking secondary peritonitis that has to be excluded. A clinical diagnose without surgical intervention is impossible in most cases. Surgical treatment has an important role in both the diagnosis and management of primary pneumococcal peritonitis, same as adequate antibiotic therapy. Primary peritonitis should be a part of the differential diagnosis of patients presenting with acute abdominal pain.

Clinical and prognostic significance of detecting CEA, EGFR, LunX, c-met and EpCAM mRNA-positive cells in the peripheral blood, tumor-draining blood and bone marrow of non-small cell lung cancer patients.

Background: Surgical treatment of early-stage non-small cell lung cancer (NSCLC) yields highest expectations for recovery. However, the frequency of further disease progression remains high since micro-metastatic disease may be undetected by conventional diagnostic methods. We test the presence and prognostic impact of circulating tumor cells (CTCs) in peripheral blood (PB), tumor-draining pulmonary blood (TDB) and bone marrow (BM) samples from NSCLC patients. Methods: The presence of circulating/disseminated tumor cells (CTCs/DTCs) was detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis in PB, TDB and BM samples before surgery in 119 stage IA-IIIA NSCLC patients (Clinical Trial NS10285). Results: NSCLC patients with the presence of carcinoembryonic antigen (CEA) mRNA-positive CTCs/DTCs in TDB and BM had significantly shorter cancer-specific survival (CSS) (P<0.013, resp. P<0.038). Patients with the presence of epithelial cellular adhesion molecule (EpCAM) mRNA-positive CTCs in TDB samples had significantly shorter CSS and disease-free survival (DFS) (P<0.031, resp. P<0.045). A multivariate analysis identified the presence of CEA mRNA-positive CTCs in the PB as an independent negative prognostic factor for DFS (P<0.005). No significant correlation of CTCs/DTCs presence and other prognostic factors was found. Conclusions: In NSCLC patients undergoing radical surgery, the presence of CEA and EpCAM mRNA-positive CTCs/DTCs is associated with poorer survival.

Microbiota Diversity in Non-Small Cell Lung Cancer Gut and Mouth Cavity Microbiota Diversity in Non-Small Cell Lung Cancer Patients.

Lung malignancies have a substantial impact on cancer incidence and mortality worldwide. Even though many factors involved in the development of the disease are known, many questions remain unanswered. Previous studies suggest that the intestinal microbiota may have a role in developing malignant diseases. According to some findings, the microbiota has proven to be a key modulator of carcinogenic processes and the immune response against cancer cells, potentially influencing the effectiveness of immunotherapy. In our study, we characterized culturable microorganisms associated with non-small cell lung cancer (NSCLC) that can be recovered from rectal swabs and mouthwash. In addition, we also explored differences in the culturable microbiota with two main types of NSCLC - adenocarcinoma (ADC) and squamous cell carcinoma (SCC). With 141 patients included in the study (86 ADC and 55 SCC cases), a significant difference was observed between the two types in seven bacterial species (Collinsella, Corynebacterium, Klebsiella, Lactobacillus, Neisseria, Rothia, and Streptococcus), including the site of origin. The relationship between microbial dysbiosis and lung cancer is poorly understood; future research could shed light on the links between gut microbiota and lung cancer development.

Cannabinoid receptor 2 expression in early-stage non-small cell lung cancers identifies patients with good prognosis and longer survival.

Background: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death with a 5-year survival of only 21%. Reliable prognostic and/or predictive biomarkers are needed to improve NSCLC patient stratification, particularly in curative disease stages. Since the endogenous cannabinoid system is involved in both carcinogenesis and anticancer immune defense, we hypothesized that tumor tissue expression of cannabinoid 1 and 2 receptors (CB1 and CB2) may affect survival. Methods: Tumor tissue samples collected from 100 NSCLC patients undergoing radical surgery were analyzed for CB1 and CB2 gene and protein expression using the quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The gene and protein expression data were correlated with disease stage, histology, tumor grading, application of chemotherapy, and survival. Additional paired tumor and normal tissue samples of 10 NSCLC patients were analyzed independently for comparative analysis of CB1 and CB2 gene expression. Results: Patients with tumors expressing the CB2 gene had significantly longer overall survival (OS) (P<0.001), cancer specific survival (CSS) (P=0.002), and disease-free survival (DFS) (P<0.001). They also presented with fewer lymph node metastases at the time of surgery (P=0.011). A multivariate analysis identified CB2 tumor tissue gene expression as a positive prognostic factor for CSS [hazard ratio (HR) =0.274; P=0.013] and DFS (HR =0.322; P=0.009), and increased CSS. High CB2 gene and protein expression were detected in 79.6% and 31.5% of the tested tumor tissue samples, respectively. Neither CB1 gene nor CB1 or CB2 protein expression affected survival. When comparing paired tumor and tumor-free lung tissue samples, we observed reduced CB1 (P=0.008) and CB1 (P=0.056) gene expression in tumor tissues. Conclusions: In NSCLC patients undergoing radical surgery, expression of the CB1 and CB2 receptor genes is significantly decreased in neoplastic versus tumor-free lung tissue. CB2 tumor tissue gene expression is strongly associated with longer survival (OS, CSS, DFS) and fewer lymph node metastases at the time of surgery. More studies are needed to evaluate its role as a biomarker in NSCLC and to investigate the potential use of CB2 modulators to treat or prevent lung cancers.

Sphingosine kinase-1 predicts overall survival outcomes in non-small cell lung cancer patients treated with carboplatin and navelbine.

Sphingosine 1-phosphate (S1P) is a bioactive lipid metabolite associated with cancer cell proliferation, survival, migration and regulation of tumor angiogenesis in various cellular and animal models. Sphingosine kinase-1 (SphK1) and S1P lyase are the main enzymes that respectively control the synthesis and degradation of S1P. The present study analyzed the prognostic and predictive value of SphK1 and S1P lyase expression in patients with non-small cell lung cancer (NSCLC), treated with either surgery alone or in combination with adjuvant carboplatin and navelbine. Formalin-fixed, paraffin-embedded tissue samples from 176 patients with NSCLC were stained immunohistochemically using antibodies against SphK1 and S1P lyase, and their expression was correlated with all available clinicopathological factors. Increased expression of SphK1 was significantly associated with shorter overall and disease free survival in patients treated with adjuvant platinum-based chemotherapy. No prognostic relevance for S1P lyase expression was observed. Collectively, the results suggest that the immunohistochemical detection of SphK1 may be a promising predictive marker in NSCLC patients treated with adjuvant platinum-based chemotherapy.

Prognostic value of Bmi-1 oncoprotein expression in NSCLC patients: a tissue microarray study.

PURPOSE: Bmi-1 is a Polycomb group member which participates in many physiological processes as well as in a wide spectrum of cancers. The aim of this study was to investigate Bmi-1 expression in non-small cell lung cancer (NSCLC) in respect to clinicopathological features and therapeutic outcomes. METHODS: Immunohistochemical staining for Bmi-1 was performed on tissue microarrays (TMAs) constructed from 179 formalin-fixed and paraffin-embedded NSCLC samples (106 squamous, 58 adeno-, and 15 large cell carcinomas). Data were subject to statistical analysis by SPSS. RESULTS: Overall evaluation of all tumor cases showed that 20 (11.43%) were negative, 37 (21.14%) showed weak, 65 (37.14%) moderate and 57 (32.57%) strong nuclear positivity for Bmi-1. Statistical analysis of our data revealed that the expression of Bmi-1 was significantly higher in stage III (P = 10(-6)) and stage IV (P = 10(-5)) tumors compared to stages I and II tumors. The administration of adjuvant chemotherapy significantly increased DFS at stage I and II patients who did not express Bmi-1 when compared to their Bmi-1 positive counterparts (P = 0.05). CONCLUSIONS: Our results suggest that Bmi-1 is significantly associated with progression of NSCLC and might serve as a prognostic marker of adverse disease outcome.

Novel markers for differentiation of lobular and ductal invasive breast carcinomas by laser microdissection and microarray analysis.

BACKGROUND: Invasive ductal and lobular carcinomas (IDC and ILC) are the most common histological types of breast cancer. Clinical follow-up data and metastatic patterns suggest that the development and progression of these tumors are different. The aim of our study was to identify gene expression profiles of IDC and ILC in relation to normal breast epithelial cells. METHODS: We examined 30 samples (normal ductal and lobular cells from 10 patients, IDC cells from 5 patients, ILC cells from 5 patients) microdissected from cryosections of ten mastectomy specimens from postmenopausal patients. Fifty nanograms of total RNA were amplified and labeled by PCR and in vitro transcription. Samples were analysed upon Affymetrix U133 Plus 2.0 Arrays. The expression of seven differentially expressed genes (CDH1, EMP1, DDR1, DVL1, KRT5, KRT6, KRT17) was verified by immunohistochemistry on tissue microarrays. Expression of ASPN mRNA was validated by in situ hybridization on frozen sections, and CTHRC1, ASPN and COL3A1 were tested by PCR. RESULTS: Using GCOS pairwise comparison algorithm and rank products we have identified 84 named genes common to ILC versus normal cell types, 74 named genes common to IDC versus normal cell types, 78 named genes differentially expressed between normal ductal and lobular cells, and 28 named genes between IDC and ILC. Genes distinguishing between IDC and ILC are involved in epithelial-mesenchymal transition, TGF-beta and Wnt signaling. These changes were present in both tumor types but appeared to be more prominent in ILC. Immunohistochemistry for several novel markers (EMP1, DVL1, DDR1) distinguished large sets of IDC from ILC. CONCLUSION: IDC and ILC can be differentiated both at the gene and protein levels. In this study we report two candidate genes, asporin (ASPN) and collagen triple helix repeat containing 1 (CTHRC1) which might be significant in breast carcinogenesis. Besides E-cadherin, the proteins validated on tissue microarrays (EMP1, DVL1, DDR1) may represent novel immunohistochemical markers helpful in distinguishing between IDC and ILC. Further studies with larger sets of patients are needed to verify the gene expression profiles of various histological types of breast cancer in order to determine molecular subclassifications, prognosis and the optimum treatment strategies.

Neoadjuvant therapy for esophageal cancer--what can we accept?

BACKGROUND/AIMS: We evaluated neoadjuvant use in managing patients with esophageal carcinoma and its effects on the surgical resection and outcomes. METHODOLOGY: Patients prior to esophageal resection were offered the opportunity to receive a neoadjuvant cytostatic regimen (CDDP + FU, CDDP, or TAX + FU). Retrospective tumor chemoresistance analysis using the MTT test was also performed. RESULTS: Seventy patients were operated from 2001 until May 2004. A total of 55 resections were performed with preoperative neoadjuvant therapy and 15 elected to only undergo surgery without neoadjuvant therapy. No deaths occurred as a result of surgery or neoadjuvant therapy, but complications included fistulas and hemorrhages. CONCLUSIONS: There was no significant difference between the postoperative complications among the neoadjuvant and non-neoadjuvant groups. This therapy therefore does not have any influence on the course or results of surgical resection. MTT testing did not demonstrate any particular usefulness in tailoring neoadjuvant therapy. Chemoresistance could only be retrospectively evaluated and the results may be affected after cytostatic therapy. The long-term outcomes have not been evaluated yet due to the short follow-up time in our patient group.

Peripheral portosystemic shunt and its selectivity changes measured on duplex ultrasound.

BACKGROUND/AIMS: Portosystemic shunts offer a symptomatic treatment for portal hypertension. Their main disadvantage is decreased perfusion of the liver with portal blood. Change of peripheral shunts into total shunts after a period of time is described. This study aims to evaluate long-term hemodynamic changes in peripheral portosystemic shunts. METHODOLOGY: The study was based on 12 patients in whom distal splenorenal shunts 8 patients) and mesocaval shunts (4 patients) were indicated respectively. Duplex sonography was used to measure the blood flow in the portal, splenic and mesenteric veins before shunt surgery and minimally 14 months postoperatively. RESULTS: It was found that the reduction of the portal blood flow was not critical and no centralization of the shunt was observed. CONCLUSIONS: Long-term blood flow in the portal vein was not severely reduced after peripheral portosystemic shunt creation, therefore the peripheral portosystemic shunt still has a role in the treatment of some patients with portal hypertension.

Sentinel lymph node in esophageal cancer before neoadjuvant therapy.

UNLABELLED: The technique of sentinel lymph node identification and biopsy has become a new popular technique for surgeon to improve staging of malignant diseases. It may also reduce the risk of complication related to standard lymphadenectomy. The method is still in experimental phase in case of esophageal cancer. A possible complication for employment of the method in this tumor is neoadjuvant therapy. The authors developed the technique for identifying and obtaining the sentinel lymph node in esophageal cancer using minimally invasive surgical technique before neoadjuvant therapy. The sentinel lymph node is detected using 99mTc-labelled nanocolloid. The authors report and discuss possible difficulties of the method in the case of a patient with detected sentinel lymph node in this way. CONCLUSION: It is possible to identify and obtain a sentinel lymph node before neoadjuvant therapy in esophageal cancer. On the other hand, the clinical significance and applicability of the method of sentinel lymph node still remains controversial in this kind of a tumor.

p53--prognostic factor of malignant transformation of Barrett's esophagus.

The most significant precancerosis in the esophageal cancer is Barrett's esophagus. The risk of malignant transformation is determined primarily in accordance with the degree of dysplastic alterations of the mucosa. Indication of "preventive" extirpation of the esophagus should be supported by other factors, for example by detection of p53 mutation or expression. The study reports on the evaluation of a group of 20 patients with Barrett's esophagus treated at the 1st Department of Surgery, the p53 level and its correlation with histological findings evaluated in these patients. A good correlation was found between the grade of Barrett's esophagus dysplasia and high p53 positivity. This correlation was also confirmed by detection of early carcinoma in patients with "preventive" extirpation of the esophagus due to a high-grade dysplasia. Preliminary results show that examination of p53 level in specimens taken from the esophageal mucosa may be helpful for the estimation of malignant potential of the dysplastic mucosa.

Brain metastases of parathyroid carcinoma: Review of the literature and a case report.

BACKGROUND: Parathyroid carcinoma is a rare tumor typically presenting with marked elevations of serum calcium concentrations and associated renal and skeletal symptoms. Parathyroid carcinoma grows slowly, but may recur in regional lymph nodes, and, in about 25% of patients, metastasizes to the lungs. METHOD: Description of a new case and review of the literature. RESULTS: We present here a patient with parathyroid carcinoma that had aggressive biological behavior with synchronous lung metastases and manifestation of brain metastases 18 month after the initial diagnosis and review earlier reports on this rare presentation. These metastases could be detected with [(18)F] fluorodeoxyglucose positron-emission tomography/computed tomography as well as with (99m)technetium-sestamibi scan. CONCLUSIONS: Except for surgery in case of isolated solitary metastases, therapeutic options in patients with brain metastases of parathyroid carcinoma are currently very limited.

Esophagogastric devascularization as the last option in the management of variceal bleeding.

Variceal bleeding is a clinical emergency that may be difficult to treat in some patients, especially those with prehepatic portal hypertension, failed sclerotherapy, and with contraindications to transjugular intrahepatic portosystemic shunt. In such patients there are few remaining options. The authors refer to three patients for whom the modified Sugiura procedure was the only remaining option for the treatment of variceal bleeding. Two of them had pre-hepatic portal hypertension, and one had hepatic cirrhosis, and in all, other standard treatment options and failed. The modified Sugiura devascularization and esophageal transection was performed without operative or postoperative complications and in the follow-up, (mean: 4.2 years), there was no recurrence of variceal bleeding. The authors recommend the modified Sugiura procedure as safe and effective for patients in whom other treatment options for variceal bleeding have failed.

Peritoneovenous shunt - modification with the use of long saphenous vein.

The authors describe their own initial experience with saphenoperitoneal modification of the peritoneovenous shunt in intractable ascites solution. Their findings with this easy type of permanent ascites drainage using the "patient's own resources" are puzzling.

Detection of minimal residual disease in lung cancer.

BACKGROUND: Even after successful radical treatment of lung cancer, patients in stages I and II of the TNM system very frequently suffer recurrence, which end lethally. Detection of subclinical residual disease after surgery is thus one of the most important emerging diagnostic methods. Minimal residual disease (MRD) is defined as the presence of isolated tumor cells or circulating cells in a patient after curative primary tumor removal and at the same time, no clinical signs of cancer. Conventional methods cannot detect minimal residual disease and hence there is a need for detection using new molecular biological methods. METHODS: We searched the PubMed database for original and review articles on minimal residual disease in lung cancer. Search words were "lung cancer", "minimal residual disease" and "detection of minimal residual disease". The publications we found were compared with the results of our own studies on the detection of minimal residual disease in lung cancer and the personal experiences are described. Examination of blood samples from 98 healthy volunteers and bone marrow from 12 patients with non inflammatory and non tumour illness, were used to determine cut-off values for specific markers in the compartments. Subsequently, expression of selected markers in tumor tissue was analysed in a pilot sample of 50 patients with lung cancer and the presence of MRD was measured as expression of values of the tested markers correlated with clinico-pathological characteristics. CONCLUSIONS: Recent studies on other malignancies apart from lung cancer have shown the importance of MRD detection in the determination of disease progression and prognosis. The methods of MRD diagnostics are based on detection of specific tumor markers. Of these, the most specific for lung cancer, appears to be the LunX protein. The best method for determining MRD is probably RT-PCR. Further studies should expand knowledge in this area: to refine understanding of the importance of tumor markers for prognosis, as well as to confirm the significance of these findings in clinical practice.

Correlation between BRCA1 expression and clinicopathological factors including brain metastases in patients with non-small-cell lung cancer.

BACKGROUND: Previously identified as a breast and ovarian cancer susceptibility gene, BRCA1 has gained major scientific interest as a potential prognostic and/or predictive marker for various tumors, including non-small-cell lung cancer (NSCLC), the leading cause of cancer related mortality worldwide. BRCA1 plays a central role in DNA damage response (DDR. It undergoes phosphorylation by various DDR kinases at different serine residues, of which ser1524 is known to be specifically phosphorylated by ATM in response to genotoxic stress. METHODS: We performed BRCA1 immunohistochemistry on several tissue microarrays (TMAs) of 113 early (I, II stage) and advanced (III, IV stage) NSCLCs, using MS110 antibody against the BRCA1 N-terminal and S1524 antibody against the phosphorylated form of BRCA1 protein at ser1524 (Abcam). Patients with III and IV stage disease were treated by adjuvant cisplatin-based chemotherapy. Staining results were correlated with overall survival (OS), disease free survival (DFS) and with the occurrence of brain metastases. RESULTS: BRCA1 S1524 nuclear positivity was significantly correlated with longer OS and DFS in stage I and II patients (P<0.05), while OS and DFS were shorter in S1524 positive stage III and IV patients (P<0.05). No significant correlation was found with brain metastases. CONCLUSION: The results show that BRCA1 phosphorylaton, at least in ser1524, differentiates the fate of early and advanced NSCLC as well as response to chemotherapy, but the underlying mechanisms are not completely understood. Detection of phosphorylated forms of BRCA1 might serve as a useful prognostic and predictive marker for patients with NSCLC.

Videothoracoscopic identification of chondromatous hamartoma of the lung.

INTRODUCTION: The main disadvantage of a videothoracoscopic procedure is the lack of touch sensation. The probability of easily finding the lesion is usually estimated according to computed tomography (CT). AIM: To find useful parameters of location of chondromatous hamartoma of the lung parenchyma in relation to its size to assess the probability of successful search via a videothoracoscopic approach only. MATERIAL AND METHODS: A group of 55 patients operated on for chondromatous hamartoma of the lung at the First Department of Surgery in Olomouc from January 2006 to June 2011 was analyzed. Initially, the tumor's longest diameter and its nearest distance to the pleural surface were measured on CT scans. Subsequently, the surgery began using the videothoracoscopic approach. A short thoracotomy with direct palpation followed when videothoracoscopy failed. RESULTS: No significant differences in age, sex and side of localization between the group with and without successful videothoracoscopic detection were found. A significant difference was found in the median size (p = 0.026) and the depth of the tumor (p < 0.0001) and in the calculated index "tumor size/depth" (p < 0.0001). Deeper analysis revealed that the parameters "depth" and "index size/depth" are considered to be good predictors but the parameter "size" is not a suitable predictor. CONCLUSIONS: The main predictors of successful videothoracoscopic detection of lung chondromatous hamartoma are considered to be the depth of the tumor in the lung parenchyma with a cut-off value ≤ 7.5 mm and the index "size/depth" with a cut-off value ≥ 1.54; the tumor size is not considered to be a good predictor.

A comparison of Direct sequencing, Pyrosequencing, High resolution melting analysis, TheraScreen DxS, and the K-ras StripAssay for detecting KRAS mutations in non small cell lung carcinomas.

BACKGROUND: It is mandatory to confirm the absence of mutations in the KRAS gene before treating metastatic colorectal cancers with epidermal growth factor receptor inhibitors, and similar regulations are being considered for non-small cell lung carcinomas (NSCLC) and other tumor types. Routine diagnosis of KRAS mutations in NSCLC is challenging because of compromised quantity and quality of biological material. Although there are several methods available for detecting mutations in KRAS, there is little comparative data regarding their analytical performance, economic merits, and workflow parameters. METHODS: We compared the specificity, sensitivity, cost, and working time of five methods using 131 frozen NSCLC tissue samples. We extracted genomic DNA from the samples and compared the performance of Sanger cycle sequencing, Pyrosequencing, High-resolution melting analysis (HRM), and the Conformité Européenne (CE)-marked TheraScreen DxS and K-ras StripAssay kits. RESULTS AND CONCLUSIONS: Our results demonstrate that TheraScreen DxS and the StripAssay, in that order, were most effective at diagnosing mutations in KRAS. However, there were still unsatisfactory disagreements between them for 6.1% of all samples tested. Despite this, our findings are likely to assist molecular biologists in making rational decisions when selecting a reliable, efficient, and cost-effective method for detecting KRAS mutations in heterogeneous clinical tumor samples.

The immunohistochemical expression of BNIP3 protein in non-small-cell lung cancer: a tissue microarray study.

Drug resistance is one of the reasons for chemotherapy failure in non-small-cell lung carcinoma (NSCLC). One of the major mechanisms of drug resistance is the inhibition of chemotherapy-induced apoptosis. Therefore, the study of novel cell death pathways could possibly enable us to overcome resistance to apoptosis in NSCLC. One of the non-caspase types of cell death is autophagy. BNIP3 protein, a Bcl-2 family member, highly expressed in some tumours, plays a key role in the induction of autophagy. In the present study, we investigated the immunohistochemical expression and subcellular localization of BNIP3 in a series of early- and late-stage non-small-cell lung carcinomas and normal bronchial tissues, and correlated this expression with the occurrence of metastasis and survival. BNIP3 was strongly expressed in the nucleus of cancer cells in 16/79 (20.3%) cases. This BNIP3 positivity did not correlate with histological grade, stage, histology type, metastatic potential, or expression of BNIP3 according to median values. No significant correlation was observed between the expression of BNIP3 and the overall survival of NSCLC patients (p = 0.55). Nor did we find any significant correlation between BNIP3 expression and the occurrence of site-specific metastasis (p = 0.85).

Identification of CD133+/nestin+ putative cancer stem cells in non-small cell lung cancer.

AIMS: No effective treatment for lung cancer exists currently. One reason for this, is the development of drug resistance, assumed to be associated with cancer stem cell (CSCs) emergence within the tumour. This pilot study aimed to identify CSCs in 121 non-small cell lung cancer (NSCLC) patient samples via detection of the expression of stem cell markers - CD133 and nestin. MATERIAL AND METHODS: Archived paraffin blocks of 121 patient samples were prepared as Tissue Microarrays (TMA). Indirect immunohistochemical staining was used to determine the level of expression of CD133 and nestin. Double immunofluorescence staining was used to investigate the co-expression of these two markers. To determine the correlation between expression of nestin and CD133 with the length of asymptomatic period and overall patient survival we used the Kaplan-Meyer analysis. RESULTS: CD133 expression was detected in 22 (19%), nestin in the epithelium in 74 (66%) and vasculature in 78 (70%) of patients. Co-expression of these two markers was found in 21 (17%) patients in less than 1% of positive cells without impact on disease free or overall survival. CONCLUSIONS: We identified CD133(+)/nestin(+) cells as novel potential markers of lung cancer CSCs.