Prognostic Factor In Lung Cancer Research Articles

Prognostic values of VEGF and IL-8 in malignant pleural effusion in patients with lung cancer

Objective: The aim of this study was to evaluate the prognostic value of VEGF and IL-8 in pleural effusion in patients with lung cancer.Materials and method: Commercially available ELISA was used to determine VEGF and IL-8 levels.Results: The level of VEGF showed significant correlations with lymph node metastasis and distant metastasis. But, IL-8 was only correlated with lymph node metastasis. Univariate and multivariate analysis revealed elevated VEGF level was an independent predictor of shorter OS and DFS.Conclusion: VEGF could be an important component that contributes to pleural effusion formation, and an important prognostic factor for lung cancer.

Abstract 5199: The biological importance of LRIG1 in lung cancer.

Abstract Leucine-rich repeats and immunoglobulin-like domains (LRIG)-1 is an endogenous inhibitor of epidermal growth factor receptor (EGFR) signaling. LRIG1 is down-regulated in several forms of human cancer. The LRIG gene family also includes LRIG2 and LRIG3. EGFR signaling is important in non-small cell lung cancer (NSCLC) and EGFR tyrosine kinase inhibitors are today considered standard treatment in patients with advanced disease. Since smoking recently was reported to down-regulate LRIG1 gene expression in lung epithelium and squamous cell carcinoma of the lung, the LRIG family of proteins may be important in lung cancer. The objective of the present study was to investigate if LRIG is a prognostic factor in non-small cell lung cancer (NSCLC) and if LRIG1 have any effects of lung cancer growth in vivo and in vitro. In the present study we analyzed the LRIG protein expression by immunohistochemistry in a tissue microarray (TMA) from surgically treated patients with NSCLC (n=366). To study the effect of LRIG1 expression on tumor growth, an animal model was used. Transgenic mice with an inducible EGFR L858R mutation were crossbred with LRIG1 knockout mice and tumor growth was assessed with micro-MRI. The impact of ectopic LRIG1 expression on lung cancer cell proliferation was studied in vitro. In the TMA, patients with high LRIG1 expression had a significantly longer median survival than negative cases (p=0.012). In the animal model, tumor progression was significantly faster in LRIG1 knockout mice 60 days after tumor induction (p=0.025) indicating that LRIG1 is of importance in the early tumor progression. Transient ectopic expression of LRIG1 inhibited lung cancer cell proliferation in vitro. In summary, LRIG1 was a positive prognostic factor in lung cancer and LRIG1 expression inhibited lung cancer growth in vivo and in vitro. This suggests that LRIG1 is of biological importance in lung cancer and that further studies of LRIG1 as a biomarker and tumor suppressor in lung cancer are warranted. Citation Format: Samuel Kvarnbrink, Karolina Edlund, Johan Botling, Patrick Micke, Roger Henriksson, Håkan Hedman, Mikael Johansson. The biological importance of LRIG1 in lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5199. doi:10.1158/1538-7445.AM2013-5199

Aldo-keto reductase superfamily and lung cancer

Aldo-keto reductase reductase (AKR) superfamily is NADPH-dependent oxidoreductase.As a rate-limiting enzyme in polyols metabolic pathway,the activation or inactivation of AKR involves in neoplastic process of lung cancer with the metabolism of environment toxic.AKR is related to drug resistance of chemotherapy,which will be the prognostic factor of lung cancer. Key words: Lung neoplasms; Neoplastic processes; Drug resistance; Aldo-keto reductase superfamily

Dilemmas in Lung Cancer Staging

The TNM staging system is the most important prognostic factor for lung cancer. The most encountered difficulties in pathologic staging of lung cancer include assessment of pleural invasion, synchronous tumor nodules, and lymph node sampling.

Overexpression and cytoplasmic accumulation of Hepl is associated with clinicopathological parameters and poor prognosis in non-small cell lung cancer

Hepl, first described in 2008, is the fourth member of the Crk-associated substrate (CAS) family and is specifically expressed in the lung. Compared to other CAS proteins, Hepl has a varying effect on cell migration in different cell types. We speculated that Hepl may play a role in lung cancer invasion and metastasis. We quantified the expression and subcellular localization of Hepl in 143 non-small cell lung cancer (NSCLC) tissues, adjacent noncancerous tissues, and eight lung cancer cell lines using Western blotting, immunohistochemistry, and immunofluorescent staining. Expression of Hepl was correlated with the clinicopathological features of NSCLC. Hepl was overexpressed in 72.3% (103/143) of the NSCLC tissues, compared to the adjacent noncancerous lung tissues (P = 0.022). Overexpression of Hepl was associated with lymph node metastasis and high TNM stage (P = 0.005 and P = 0.045, respectively). Kaplan-Meier survival curves and the log-rank test indicated that overexpression of Hepl correlated with poorer overall survival in NSCLC (P < 0.001), and Cox regression analysis demonstrated that overexpression of Hepl was an independent prognostic factor in NSCLC. Furthermore, cytoplasmic accumulation of Hepl was observed in a high metastatic potential lung cancer cell lines (H1299 and BE1), but not in low metastatic potential cell lines (LTE and A549). This study reveals that Hepl is overexpressed in the nucleus and aberrantly accumulates in the cytoplasm of NSCLC cells, and indicates that Hepl may play a role in the progression of lung cancer, including lymph node metastasis and TNM stage. Additionally, Hepl may be a useful prognostic factor in lung cancer.

188P - Tropomyosin-Related Kinase B is a Therapeutic Target and Prognostic Factor for Aggressive Lung Cancer Including Lcnec

ABSTRACT Background Lung cancer is one of the most common types of cancer, accounting for more deaths than any other types of cancer. Tropomyosin-related kinase B (TrkB) has previously been shown to be important in tumor progression in neuroblastoma, pancreatic cancer, and prostate cancer. However, little is known about biological significance of TrkB in human lung cancer. Here we investigate if TrkB may be a therapeutic target and prognostic factor for lung cancer. Methods Surgically resected specimen; The expression of TrkB and its ligand BDNF (Brain-derived neurotrophic factor) were investigated in 104 patients with primary lung cancers (8 small cell carcinomas, 11 large cell neuroendocrine carcinomas, 10 large cell carcinomas, 20 adenocarcinomas, 55 squamous cell carcinomas) by immunohistochemical staining. In vitro assay; Large cell neuroendocrine carcinoma (LCNEC) cell lines (NCI-H460 and NCI-H810) expressing TrkB were used. TrkB-siRNA and TrkB tyrosine kinase inhibitor (K252a) were used to inhibit TrkB. BDNF-siRNA was used to inhibit BDNF. Cell proliferation and invasion were evaluated by MTT and Transwell assays, respectively. Results 1) There were significantly higher TrkB and BDNF expressions in LCNEC cases than any other histological types. LCNEC cases also had poorer prognosis than any other histological types. 2) Higher expression of TrkB positively correlated with disease free survival (p Conclusions These data suggests that BDNF/TrkB signal is important in LCNEC and TrkB is a potential therapeutic target and prognostic factor for aggressive lung cancer including LCNEC. Disclosure All authors have declared no conflicts of interest.

Association of Worse Prognosis With an Aberrant Diurnal Cortisol Rhythm in Patients With Advanced Lung Cancer

A flatter diurnal rhythm of cortisol has been reported to be associated with early mortality in patients with metastatic breast cancer. The clinical stage of disease at the time of diagnosis and the patient's performance status (PS) are known to be important prognostic factors for lung cancer (LC) survival. The authors examined the relationship between diurnal cortisol rhythms and these prognostic factors in patients with advanced LC. Cortisol concentrations were measured in saliva samples collected from 52 patients (37 males/15 females) with advanced LC and from 56 healthy subjects (32 males/24 females) to characterize the diurnal cortisol rhythm, specifically the cortisol awakening response (CAR) and diurnal cortisol decline (DCD). Variations of CAR and DCD in the patients were analyzed according to their clinical disease stage and PS score, and the differences in CAR and DCD between patients and healthy controls were compared. The patient group showed significantly reduced diurnal cortisol secretory activity and rhythmicity, compared with healthy controls. When the patients were subgrouped according to their clinical disease stage, patients with stage 4 disease showed significantly reduced CAR and flatter DCD compared with the healthy controls. However, the CAR and DCD in patients with stage 3a and 3b disease were comparable to those of healthy controls. Neither the CAR nor the DCD showed stepwise changes as the disease stage worsened. When patients were subgrouped according to their Eastern Cooperative Oncology Group (ECOG) PS score, there was stepwise reduction in the CAR and flattening of the DCD as the PS score increased. Both an abolished CAR and a flattened DCD were common in patients with ECOG PS scores of 3 and 4. These results indicate that alteration of the diurnal cortisol rhythm in patients with advanced LC is more closely associated with their PS score than with their clinical disease stage. Gradual alteration of the CAR and DCD, indicative of loss of 24-h cortisol rhythm, in concert with increase in PS score implies that endogenous circadian rhythms may also be disintegrating as the PS score worsens in these patients. (Author correspondence: ryunsup@yahoo.co.kr)

Concurrent chemoradiotherapy in locally advanced non-small cell lung cancer—Prognostic factors and reasons for treatment failure in group of patients 1996–2008

Introduction: Concurrent chemoradiation is the standard therapy in fit patients with locally advanced inoperable non-small cell lung cancer. Aim of this retrospective study is analysis of survival in relation to several variables and analysis of treatment failure.

Gene polymorphisms of folate metabolizing enzymes and susceptibility to lung adenocarcinoma in Serbia.

e12020 Background: Methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) are important enzymes of the folate metabolism and are suggested as new prognostic factors for lung cancer. Cytosine to thymine transition at nucleotide 677 (C677T) leads to reduced MTHFR activity. The TS promoter has a tandem repeat polymorphism (2R, 3R) and a guanine to cytosine transition in the 3R allele related to TS protein expression. The aim of this study was to analyze the association of MTHFR and TS polymorphisms with lung adenocarcinoma in Serbia. Methods: A case-control study including 55 late-stage lung adenocarcinoma patients and 53 healthy subjects was performed. Restriction fragment length polymorphism analysis was used for MTHFR and TS genotyping. Depending on the presence of high (3RG) or low (2R, 3RC) expression alleles, TS functional groups were subclassified into HH (3RG/3RG), HL (2R/3RG, 3RG/3RC) and LL (2R/2R, 2R/3RC, 3RC/3RC) groups. Descriptive analyses included genotype and allelic frequencies; the odds ratio (OR) and 95 % confidence interval (CI) were calculated as an estimate of relative risk. Significance was considered for p &lt; 0.05. Results: The distribution of the MTHFR variants in patients vs. controls was 61.8 % vs. 24.5 % for CC, 32.7 % vs. 62.3 % for CT and 5.5 % vs. 13.2 % for TT. A significant difference in CC vs. TT+CT MTHFR genotype distribution was observed between patients and controls (χ2 = 13.79; OR = 4.98; 95 % CI, 2.14 – 11.61). There was no significant association between the TS polymorphisms and the risk of lung adenocarcinoma occurrence, but in the CT+TT MTHFR subgroup, a nonsignificant difference in LL vs. HL+HH TS genotype distribution was observed between patients and controls (χ2 = 0.04; OR = 1.07; 95% CI, 0.31 – 3.67). Conclusions: A significant corelation between the CC MTHFR genotype and lung adenocarcinoma occurence in Serbia was found. Also, there was no significant correlation with lung adenocarcinoma occurence in the CT+TT MTHFR subgroup for carriers of the LL TS genotype. As this study was performed on a relatively small sample size further large case-control studies including analysis of gene-gene interactions with genes coding for other folate metabolism enzymes is needed.

ERBB2-induced inflammation in lung carcinogenesis

ERBB2/HER2/NEU, a member of the epidermal growth factor receptor family, is overexpressed in more than 25 % of non-small cell lung cancer and is considered to be a significant and independent prognostic factor in lung cancer. Here we generated a lung specific HER2 overexpressing transgenic mouse model. In this model, HER2 was driven by the human surfactant protein-C promoter to investigate the role of the HER2 oncogene in pulmonary carcinogenesis and progression. Notably, significant pathological changes, including lymphocyte infiltration and mesenchymal cells hyperplasia, were found in the lung tissue of transgenic mice aged from 4 to 12 months. The occurrence and severity of those lesions increased as the mice aged. Some inflammatory factors, such as tumor necrosis factor, interleukin 1 and interleukin 6, were upregulated in lung tissue of transgenic mice compared with that of wild-type mice, implying that long-term HER2 overexpression could induce serious lung inflammation and some precancerous lesions. This model would be useful for studying the mechanism of HER2 involvement in lung carcinogenesis and for understanding the relationship between carcinogenesis and inflammation.

Prognostic factors in lung cancer in a defined geographical area over two decades with a special emphasis on gender

Many studies over recent decades report an increasing incidence of lung cancer in female patients. Female gender is often reported as a good prognostic factor. The aim of the present study was to investigate prognostic factors with a special emphasis on gender. During 1989-2008, 1497 patients in eastern Scania, a part of southern Sweden with 202,000 inhabitants, were referred to one Central Hospital and prospectively registered. All patients were grouped into four 5-year periods and were analysed for occurrence of lung cancer, patient performance status, types and stages of lung cancer and the relation to gender. The incidence of lung cancer more than doubled in women. The proportion of adenocarcinomas increased in females and in males to 57% (P=0.028) and 42% (P=0.001), respectively, while the frequency of small cell lung carcinomas (SCLCs) decreased in both genders to approximately 14%. Females had significantly more frequent stage 1 (16.6%) and higher surgery rate (23.1%) than males (12% and 18.2%, respectively). Females showed a higher 5-year survival rate than males (20.1% and 11.5%, respectively; P<0.001). Patients with non-small cell lung carcinoma (NSCLC) had a higher 5-year survival rate than those with SCLC (16.5% and 7.5%, respectively; P<0.01); however, there was no significant survival difference in females between NSCLC and SCLC. Female patients exhibited longer survival than males for both NSCLC and SCLC, and this was not explained by a higher frequency of stage 1 or surgery in NSCLC.

RET finger protein expression is associated with prognosis in lung cancer with epidermal growth factor receptor mutations

The RET finger protein (RFP) is a transcription factor belonging to the TRIM (tripartite motif) superfamily of proteins. RFP is expressed in a variety of human and rodent tumor cell lines and in several kinds of human cancer. Expression of RFP is associated with prognosis of colon and endometrial cancers. In the present study, we evaluated the expression of RFP in lung cancer and assessed its clinical significance. Tissue microarrays were constructed from 108 cases of lung cancer, and the sections were analyzed for RFP expression by immunohistochemistry. RFP expression was detected in the nucleus in 66.7% of lung cancer tissues examined. RFP expression was statistically significantly associated with thyroid transcription factor 1 (TTF-1) expression (P= 0.028). However, no significant association was observed between RFP expression and other clinicopathological or genetic factors, including epidermal growth factor receptor (EGFR) mutations. Interestingly, we found that RFP expression correlated with poor prognosis in patients with EGFR mutations (P= 0.032). Our results suggest that RFP has a role in mutated EGFR signaling and that RFP status may be a prognostic factor for lung cancer with EGFR mutations.

Pathway-based identification of a smoking associated 6-gene signature predictive of lung cancer risk and survival

Smoking is a prominent risk factor for lung cancer. However, it is not an established prognostic factor for lung cancer in clinics. To date, no gene test is available for diagnostic screening of lung cancer risk or prognostication of clinical outcome in smokers. This study sought to identify a smoking associated gene signature in order to provide a more precise diagnosis and prognosis of lung cancer in smokers. An implication network based methodology was used to identify biomarkers by modeling crosstalk with major lung cancer signaling pathways. Specifically, the methodology contains the following steps: (1) identifying genes significantly associated with lung cancer survival; (2) selecting candidate genes which are differentially expressed in smokers versus non-smokers from the survival genes identified in Step 1; (3) from these candidate genes, constructing gene coexpression networks based on prediction logic for the smoker group and the non-smoker group, respectively; (4) identifying smoking-mediated differential components, i.e., the unique gene coexpression patterns specific to each group; and (5) from the differential components, identifying genes directly co-expressed with major lung cancer signaling hallmarks. A smoking-associated 6-gene signature was identified for prognosis of lung cancer from a training cohort (n=256). The 6-gene signature could separate lung cancer patients into two risk groups with distinct post-operative survival (log-rank P<0.04, Kaplan-Meier analyses) in three independent cohorts (n=427). The expression-defined prognostic prediction is strongly related to smoking association and smoking cessation (P<0.02; Pearson's Chi-squared tests). The 6-gene signature is an accurate prognostic factor (hazard ratio=1.89, 95% CI: [1.04, 3.43]) compared to common clinical covariates in multivariate Cox analysis. The 6-gene signature also provides an accurate diagnosis of lung cancer with an overall accuracy of 73% in a cohort of smokers (n=164). The coexpression patterns derived from the implication networks were validated with interactions reported in the literature retrieved with STRING8, Ingenuity Pathway Analysis, and Pathway Studio. The pathway-based approach identified a smoking-associated 6-gene signature that predicts lung cancer risk and survival. This gene signature has potential clinical implications in the diagnosis and prognosis of lung cancer in smokers.

Cyclooxygenase-2 Expression is not a Marker of Poor Survival in Lung Cancer

Cyclooxygenase-2 (COX-2) has been claimed to play role in carcinogenesis and be related to a bad prognosis in tumours. The aim of this study was to investigate the relationship between COX-2 expression and clinical and pathological parameters in early and advanced stage lung cancer patients. A total of 73 patients with lung cancer (27 adenocarcinomas, 33 squamous cell carcinomas, 4 large cell carcinomas and 9 small cell cancer) were analysed retrospectively. COX-2 expression was evaluated by immunohistochemistry in resection materials or lung biopsies. Tumor cells demonstrating more intense staining than smooth muscle and endothelial cells were recorded as COX-2 positive. We investigated the correlation between increased COX-2 expression and histological type of the tumor, the stage of the disease and survival. COX-2 expression was observed in 55% of the adenocarcinomas, 45% of the squamous cell carcinomas and 22% of the small cell carcinomas. No correlation was apparent between COX-2 expression and disease stage, histological type and the survival. The results of this study do not support COX-2 expression as an independent prognostic factor in lung cancer. However, since results of the literature are different, further studies made in larger series are needed.

Nuclear factor erythroid-derived 2-like 2 (Nrf2) and DJ1 are prognostic factors in lung cancer

Nuclear factor erythroid-derived 2-like 2 (Nrf2) controls the expression of several enzymes that are protective against oxidative stress. We investigated the expression of nuclear factor erythroid-derived 2-like 2, DJ1 (Nrf2 stabilizer), and sulfiredoxin in a large set of lung carcinomas. The cases were analyzed immunohistochemically with antibodies to nuclear factor erythroid-derived 2-like 2, DJ1, and sulfiredoxin with the results being compared with histologic and clinical data. Significant differences were observed in the expression of DJ1 and sulfiredoxin between various types of lung tumors, while expression of nuclear factor erythroid-derived 2-like 2 was more constant. Patients with tumors with cytoplasmic (P = .033) or nuclear (P = .003) DJ1 positivity exhibited worse survival. Separately in squamous cell carcinomas, there was a tendency toward worse survival with both cytoplasmic (P = .013) and nuclear (P = .071) DJ1 positivity. Patients with a strong nuclear factor erythroid-derived 2-like 2 expression in their tumors had worse survival (P = .006). In the Cox regression analysis, nuclear factor erythroid-derived 2-like 2 was an independent prognostic factor (P = .012) along with the T status (P = .008) and DJ1 cytoplasmic positivity (P = .028). Interestingly, smokers and ex-smokers had significantly more sulfiredoxin expression in their tumors (P < .001); and in patients receiving cytostatic drugs or radiation therapy, sulfiredoxin expression predicted a poor prognosis (P = .038). Nuclear factor erythroid-derived 2-like 2 and its stabilizing protein DJ1 affect the prognosis of patients with lung cancer by inducing an elevated stress response to oxidative damage. There were differences in the expression of sulfiredoxin and DJ1 between different lung tumor types, suggesting that the pathways involved in combating oxidative stress vary in different lung cancer types.

Different efficacy of CT screening for lung cancer according to histological type: Analysis of Japanese-smoker cases detected using a low-dose CT screen

The efficacy of CT screening for lung cancers is still a controversial issue, although one of the recently publicized large randomized controlled trials of this methodology, the National Lung Screening Trial (NLST), reported a decrease in the lung cancer-specific mortality for heavy smokers. We here performed case-matched comparative analyses, as a retrospective study, of three lung cancer arms detected by CT screen, X-ray screen, and by individual analysis of the clinicopathological features and outcomes in smokers from a symptomatic-prompted group of patients. We also considered the impacts of various potential biases in this cohort. The total study cohort comprised 136 patients in the CT screen group, 263 in the X-ray screen group and 254 in the symptomatic-prompted group. The ratio of stage IA cancers in the CT screen group was 67.7% and the ratio of advanced cases (i.e. stages IIIB+IV) was 12.5%. The percentage of bronchioloalveolar carcinoma (BAC) was 28.7% in the CT screen group. The 5-year survival rates were 82.4% in the CT screen group, 38.0% in the X-ray screen group and 17.8% in the symptomatic-prompted group. CT screening was found to be an independent prognostic factor for lung cancer even when BAC cases were eliminated (HR 0.35, P<0.01). Based on our sub-analysis by individual histological sub-type, CT screen lung cancer cases had a better survival rate than non-screened patients, which included adenocarcinoma, squamous cell carcinoma and large/small cell carcinoma. However, by multi-variant analysis a CT scan would not be expected to reduce the risk of lung cancer mortality in patients with large/small cell carcinoma, although would be expected to reduce the risk of lung cancer death by 80% in cases of both adenocarcinoma and squamous cell carcinoma. In conclusion, our current findings indicate that CT screening for lung cancer is an effective strategy for smokers and that patients with adenocarcinoma and squamous cell carcinoma of all variant histological types may benefit from this test. In this regard, early stage large/small cell carcinomas are insufficiently detected by the existing annual screening system.

Efficacy of CT screening for lung cancer in never-smokers: Analysis of Japanese cases detected using a low-dose CT screen

CT-screening for lung cancer is fairly widely used for both smokers and never-smokers in East Asia because the mortality rate for never-smokers due to this cancer is relatively high in this region. We performed comparative analyses, as a retrospective study, on three lung cancer arms detected by CT-screen, X-ray-screen, and via analysis of clinicopathological features and outcomes in never-smokers from a symptomatic-prompted group of patients. The total study cohort comprised 218 patients in CT group, 160 in X-ray group, and 82 in symptomatic-prompted group. The percentage of bronchioloalveolar carcinoma (BAC) was 65.1% in CT-screen group. The ratio of stage IA tumors in CT-screen group was 88.5% and the ratio of advanced cases (i.e. stages IIIB+IV) was 2.3%. The 5-year-survival rates were 95.0% in CT-screen, 73.0% in X-ray-screen and 40.0% in symptomatic-prompted group. We performed further sub-analysis which excluded pure BACs (i.e. Noguchi types A and B) or pure GGOs within a 10mm diameter because this is indicative of a very favorable prognosis. Based on this sub-analysis the number of the subjects in each group became 76 in CT group; 140 in X-ray group and 77 in symptomatic-prompted group. The principal characteristics of the patients such as age and sex became almost even in the three arms. In CT-screen subgroup, the ratio of stage IA cancer was 69.7% and of advanced cases was 6.6%. This advanced ratio was lower than both X-ray-screen (22.1%) and symptomatic-prompted (61.9%) groups. The 5-year-survival rates were 89.9% among CT-screen group patients, 72.6% for X-ray screen cases and 39.1% in symptomatic-prompted group. A CT-screen was found to be one of the independent prognostic factors for lung cancer (HR, 0.28; 95% CI, 0.12–0.72) and based on this would be expected to reduce the risk of lung cancer death by 78% compared with non-screened cases. In conclusion, CT will improve the survival rate and decrease the rate of advanced cancers in never-smokers via the existing annual screening system. CT-screening is also an independent prognostic improvement factor in never-smokers, and will therefore reduce the risk of lung cancer death.

Prognostic factors in stage III non-small cell lung cancer: a review of conventional, metabolic and new biological variables

Lung cancer is one of the most frequently occurring neoplasms and usually has a poor prognosis because most of the patients present with advanced or metastatic disease at the time of diagnosis. Numerous prognostic factors (PFs) have been studied, but the two most prominent, having both prognostic and operational values, are disease stage and performance status. Even if the literature on PFs in lung cancer is impressive, the number of publications specifically dealing with PFs in stage III non-small cell lung cancer (NSCLC) is limited. We reviewed the literature on this topic and separated the available information into three groups: conventional PFs, metabolic criteria (standardized uptake value [SUV] measured on(18)F-FDG-PET) and new biomarkers. Performance status and the distinction between stage IIIA and IIIB confirmed their prognostic value in stage III NSCLC. Other conventional PFs have been suggested such as age, weight loss, response to treatment and some characteristics describing the locoregional extension of the tumour. There is a place for the SUV as a PF for survival in early NSCLC, but its role in stage III NSCLC has to be further assessed. Some new biomarkers involved in cell cycle regulation or in apoptosis have been shown to have potential value. Their role needs to be confirmed in large prospective studies including conventional PFs to determine their independent value as a PF in stage III NSCLC. In conclusion, few PFs have been well evaluated in stage III NSCLC. New studies, taking into account the modifications derived from the 7th international staging system of the UICC, have to be performed.

Cyclooxygenase‐2 expression in lung cancer cells evaluated by immunocytochemistry

Cyclooxygenase-2 (COX-2) expression may be a prognostic factor in lung cancer. In previous studies, COX-2 expression has almost exclusively been evaluated with immunohistochemical methods performed on histology sections of tissue biopsies. However, in clinical practice, lung cancer is often diagnosed with cytological techniques only. We present methodology and results from analysis of COX-2 expression with immunochemistry on cytological material in 53 patients with lung cancer. Preparation and staining with the method established at our laboratory were easy to perform and resulted in good quality slides. The percentage COX-2-stained cells and the intensity of staining varied widely between and within the different cases. The proportion of positively stained tumor cells was as follows: <1% in 20 patients, 1-10% in 7 patients, 11-50% in 17 patients, and more than 50% in 9 patients. In 17 cases, groups of cells with different intensity of COX-2 staining were found in the same slide. In conclusion, immunocytochemical analysis of COX-2 expression is technically easy to perform with routine diagnostic procedures. There is a great variation in the proportion of COX-2-positive cells among patients and in the intensity of staining among individual cells in many single cases.

Expression of CD44s and CD44v6 in Lung Cancer and Their Correlation with Prognostic Factors

CD44, a transmembrane glycoprotein receptor, plays a major role in tumor progression and metastasis. To evaluate the expression of CD44 standard (CD44s) and its variant 6 (CD44v6) in normal and neoplastic lung tissue and correlate it with prognostic factors in lung cancer. The study included 52 non-small cell lung carcinomas (NSCLC) (21 squamous cell carcinomas and 31 adenocarcinomas), 15 small cell lung carcinomas (SCLC) and 8 carcinoid tumors. Expression of CD44s and CD44v6 was evaluated by immunohistochemistry and correlated with lung cancer prognostic factors. All squamous cell carcinomas expressed both CD44s and CD44v6. Adenocarcinomas expressed CD44s in 39% of cases and CD44v6 in 45%. Carcinoid tumors expressed only CD44s in 88% of cases. All SCLCs were negative for both CD44s and CD44v6. A restricted panel consisting of CD44s and CD44v6 will discriminate NSCLC from SCLC with a sensitivity of 67% and a specificity of 100%. In adenocarcinoma CD44s expression was significantly correlated with lymph node metastases (p=0.007) while CD44v6 expression was more significantly associated with tumor size (p=0.0032). CD44s and CD44v6 are expressed in certain types of lung cancer. In adenocarcinoma CD44s and CD44v6 expression is significantly correlated with lymph node metastases and tumor size.