Stage Patient Survival Research Articles

Endometrial cancer risk factors, treatment, and survival outcomes as per the European Society for Medical Oncology (ESMO) - European Society of Gynaecological Oncology (ESGO) - European Society for Radiotherapy and Oncology (ESTRO) risk groups and International Federation of Gynecology and Obstetrics (FIGO) staging: An experience from developing world.

There is limited data on endometrial cancer from developing countries. The risk groups as defined by the ESMO-ESGO-ESTRO and their recommendations for adjuvant treatment have redefined the management protocols. In this retrospective analysis, the outcomes are assessed in the light of the new risk groups and FIGO staging. One hundred and two patients of endometrial cancer reporting to the Department of Radiation Oncology from 2015 to 2019 were analysed retrospectively. Patients were stratified as per the ESMO-ESGO-ESTRO risk groups and FIGO staging. Patients were analysed for demographic profile, histopathology details, FIGO stage, treatment modalities received as per the ESMO-ESGO-ESTRO risk groups and the outcomes in terms of disease free survival and overall survival. A total of 102 patients were analysed. The mean age at presentation was 57.7 years. Seventy four percent (74.41%) were stage I patients, 14.7 % were stage II, 8.8% were stage III and remaining 2% were stage IV. The mean disease free survival for the patients in FIGO stage I, II, III and IV were found to be 63.5 (59.9 - 67) months, 60.5 (54.2 - 66.9) months, 30.9 (21.5 - 40.2) months and 15.4 (7.8 - 23.0) months respectively. The 5-year overall survival of patients in Stage I was 90.3%. The 3-year mortality of Stage III patients was 58.3%. While there was no mortality observed among Stage II patients, none of the Stage IV patient survived beyond 20 months. The 5-year disease-free survival for patients in Low Risk (LR) group, Intermediate Risk (IR) group and High Risk (HR) group was found to be 91.3%, 90% and 87% respectively. None of the patient in High Intermediate Risk (HIR) group experienced progression of disease and 33.3% patients in advanced group were disease free at 2 years follow-up. The multivariate analysis showed that lymph node involvement is significantly associated with disease-free (p=0.03) and overall survival (p=0.04). Even in the developing world, majority of patients present in early stage with survival outcomes comparable to the West. FIGO stage and lymph node involvement continue to be the most important prognostic markers for disease outcomes.

Prognostic Significance of Cytoplasmic SPNS2 Expression in Patients with Oral Squamous Cell Carcinoma.

Background and Objectives: Oral squamous cell carcinoma (OSCC) is a malignant disease with a particularly high incidence in Taiwan. Our objective in this study was to elucidate the involvement of sphingolipid transporter 2 (SPNS2) expression and SPNS2 protein expression in the clinicopathological indexes and the clinical outcomes of OSCC patients. Materials and Methods: Immunohistochemistry analysis was performed for SPNS2 protein expression in samples from 264 cases of OSCC. Correlations of SPNS2 expression with clinicopathological variables and patient survival were analyzed. Results: Our results revealed that the cytoplasmic protein expression of SPNS2 in OSCC tissue specimens was lower than in normal tissue specimens. Negative cytoplasmic protein expression of SPNS2 was significantly correlated with T status and stage. Kaplan–Meier survival curve analysis revealed that negative cytoplasmic SPNS2 expression was predictive of poorer overall survival of OSCC patients in stage III/IV. We also determined that low SPNS2 expression was an independent prognostic factor related to overall survival among OSCC patients in stage III/IV from univariate Cox proportional hazard models. Multivariate Cox proportional hazard models revealed that cytoplasmic SPNS2 expression, T status, lymph node metastasis, and histological grade were independent prognostic factors for survival. Conclusions: Overall, this study determined that SPNS2 protein may be a useful prognostic marker for OSCC patients and potential therapeutic target for OSCC treatment.

A Leukocyte Infiltration Score Defined by a Gene Signature Predicts Melanoma Patient Prognosis.

Melanoma is the most aggressive type of skin cancer in the United States with an increasing incidence. Melanoma lesions often exhibit high immunogenicity, with infiltrating immune cells playing important roles in regression of tumors occurring spontaneously or caused by therapeutic treatment. Computational and experimental methods have been used to estimate the abundance of immune cells in tumors, but their applications are limited by the requirement of large gene sets or multiple antibodies. Although the prognostic role of immune cells has been appreciated, a systematic investigation of their association with clinical factors, genomic features, prognosis and treatment response in melanoma is still lacking. This study, identifies a 25-gene signature based on RNA-seq data from The Cancer Genome Atlas (TCGA)-Skin Cutaneous Melanoma (TCGA-SKCM) dataset. This signature was used to calculate sample-specific Leukocyte Infiltration Scores (LIS) in six independent melanoma microarray datasets and scores were found to vary substantially between different melanoma lesion sites and molecular subtypes. For metastatic melanoma, LIS was prognostic in all datasets with high LIS being associated with good survival. The current approach provided additional prognostic information over established clinical factors, including age, tumor stage, and gender. In addition, LIS was predictive of patient survival in stage III melanoma, and treatment efficacy of tumor-specific antigen vaccine. IMPLICATIONS: This study identifies a 25-gene signature that effectively estimates the level of immune cell infiltration in melanoma, which provides a robust biomarker for predicting patient prognosis.

1366P - The impact of the new TNM classification on survival of patients in stage III non-small cell lung cancer

1366P - The impact of the new TNM classification on survival of patients in stage III non-small cell lung cancer

The Association Between Mutations in BRAF and Colorectal Cancer–Specific Survival Depends on Microsatellite Status and Tumor Stage

Colorectal tumors with mutations in BRAF and microsatellite stability (MSS) have been associated with adverse outcomes of patients. Combined tests for microsatellite instability-high (MSI-H) and BRAF mutations might therefore be used in risk assessment, particularly for patients with stage II tumors. We investigate the stage-specific prognostic value of combined testing for MSI-H and BRAF for patients with colorectal cancer. We performed a retrospective analysis of colorectal tumor samples collected from 1995 patients at 22 hospitals in Germany, between 2003 and 2010. Samples were analyzed for MSI-H using an established mononucleotide marker panel; BRAF mutations (BRAFV600E) were detected by Sanger sequencing or in tissue microarray blocks using immunohistochemistry. Cancers were assigned to categories of having MSS without mutations in BRAF, MSS with mutant BRAF, MSI-H without mutations in BRAF, and MSI-H with mutant BRAF. Weinvestigated the association between tumor categories with clinical and pathologic features and patient's overall, disease-specific, and recurrence-free survival (median follow-up time, 5.1 y). Tumors were stage I in 364 (18%), stage II in 678 (34%), stage III in 673 (34%), andstage IV (14%) in 280 patients. Sixty-three percent of tumors were located in thecolon and 37% in the rectum. Most tumors (85%) had MSS without mutations in BRAF, 3% had MSS with mutant BRAF, 7% had MSI-H without mutations in BRAF, and5% had MSI-H with mutant BRAF. In patients whose tumors were MSI-H, mutation of BRAF did not significantly affect survival time. Patients whose tumors had MSS with mutant BRAF had significantly reduced overall survival (hazard ratio [HR], 2.16; 95% CI, 1.54-3.04; P < .001), disease-specific survival (HR, 2.59; 95% CI, 1.77-3.79; P < .001), and recurrence-free survival (HR, 2.45; 95% CI, 1.70-3.52; P < .001) than patients whose tumors had MSS without BRAF mutation. Although BRAF mutations intumors with MSS were associated with disease-specific survival of patients with stage III or IV tumors (P < .001), these features did not affect survival of patients with stage II tumors (P=.639). In an analysis of almost 2000 patients with colorectal cancer, we found BRAF mutations to reduce survival of patients in stage III or IV (but not stage II) tumors with MSS. These findings do not support testing stage I or II colorectal tumors for BRAF mutations, although additional large studies are needed.

The Fibrinogen to Mean Platelet Volume Ratio Can Predict Overall Survival of Patients with Non-Metastatic Gastric Cancer.

PurposeFibrinogen and platelets have been reported to play important roles in tumorigenesis and cancer progression. The aim of this research was to investigate the combination of functions of fibrinogen, platelets, and mean platelet volume (MPV) in predicting the survival of patients with gastric cancer (GC).Materials and MethodsA retrospective study was conducted with 1,946 patients with GC and 299 patients with benign gastric tumor to analyze their fibrinogen, platelet, and MPV levels, and other clinicopathological characteristics along with their prognoses. Several indicators were evaluated along with fibrinogen, platelets, and MPV and their prognostic abilities were assessed. Univariate and multivariate survival analyses were conducted to determine the independent risk factors for overall survival.ResultsIncreased levels of fibrinogen, platelets, and MPV were observed with the progress of the GC stages. Elevated fibrinogen, platelets, and the combined indicators, including fibrinogen*MPV (FM), platelet*fibrinogen*MPV (PFM), fibrinogen/MPV (FMR), platelet*fibrinogen (PF), platelet*fibrinogen/MPV (PFMR), platelet*MPV (PM), and platelet/MPV (PMR), foreboded poor prognosis. Meanwhile fibrinogen and FMR can be considered as independent risk factors for overall survival in patients with non-metastatic GC. But these indicators can hardly predict survival of patients in stage IV.ConclusionsElevated fibrinogen, platelets, and MPV levels were in accordance with advanced stages, and fibrinogen, platelet, and MPV, in combination, can be used to predict survival of patients with non-metastatic GC. FMR was an independent prognostic factor for overall survival of patients with GC.

ED10.03 New Developments in Radiotherapy of Stage III NSCLC

ED10.03 New Developments in Radiotherapy of Stage III NSCLC

Relationship Between Metformin Use and Recurrence and Survival in Patients With Resected Stage III Colon Cancer Receiving Adjuvant Chemotherapy: Results From North Central Cancer Treatment Group N0147 (Alliance).

Preclinical and epidemiological data suggest that metformin might have antineoplastic properties against colon cancer (CC). However, the effect of metformin use on patient survival in stage III CC after curative resection is unknown. The survival outcomes were comparable regardless of the duration of metformin use. Before randomization to FOLFOX (folinic acid, 5-fluorouracil, oxaliplatin) with or without cetuximab, 1,958 patients with stage III CC enrolled in the N0147 study completed a questionnaire with information on diabetes mellitus (DM) and metformin use. Cox models were used to assess the association between metformin use and disease-free survival (DFS), overall survival (OS), and the time to recurrence (TTR), adjusting for clinical and/or pathological factors. Of the 1,958 patients, 1,691 (86%) reported no history of DM, 115 reported DM with metformin use (6%), and 152 reported DM without metformin use (8%). The adjuvant treatment arms were pooled, because metformin use showed homogeneous effects on outcomes across the two arms. Among the patients with DM (n = 267), DFS (adjusted hazard ratio [aHR], 0.90; 95% confidence interval [CI], 0.59-1.35; p = .60), OS (aHR, 0.99; 95% CI, 0.65-1.49; p = .95), and TTR (aHR, 0.87; 95% CI, 0.56-1.35; p = .53) were not different for the metformin users compared with the nonusers after adjusting for tumor and patient factors. The survival outcomes were comparable regardless of the duration of metformin use (<1, 1-5, 6-10, ≥11 years) before randomization (ptrend = .64 for DFS, ptrend = .84 for OS, and ptrend = .87 for TTR). No interaction effects were observed between metformin use and KRAS, BRAF mutation status, tumor site, T/N stage, gender, or age. Patients with stage III CC undergoing adjuvant chemotherapy who used metformin before the diagnosis of CC experienced DFS, OS, and TTR similar to those for non-DM patients and DM patients without metformin use. The present study did not find any relationship between metformin use or its duration and disease-free survival, time to recurrence, and overall survival in a large cohort of patients with resected stage III colon cancer receiving adjuvant FOLFOX (folinic acid, fluorouracil, oxaliplatin)-based chemotherapy. This relationship was not modified by KRAS or BRAF mutation or DNA mismatch repair status. Metformin use did not increase or decrease the likelihood of chemotherapy-related grade 3 or higher adverse events.

Abstract 713: Determining the role of tumor-infiltrating B cells in NSCLC

Abstract Recent studies in human non-small cell lung cancer (NSCLC) have shown that upregulation of B cell-associated genes strongly correlate with early stage patient survival. After analyzing a gene expression database of lung tumors we showed that CD79A, a pan-B cell marker, had the strongest predictive value, suggesting that B cells are playing a crucial role in NSCLC immunity. In order to evaluate this we first examined where this genetic signature was originating from. We observed that patients with high levels of B cell-related genes also showed high numbers of CD79A+ B cells intimately associated with the tumor, but not being expressed by tumor cells themselves. A closer look at tumor-infiltrating B cells (TIL-B cells) by IHC and flow cytometry of fresh patient tumor samples has confirmed their presence and allowed us to begin elucidating their phenotype. Interestingly, we have found that not all early stage patients have detectable levels of TIL-B cells, but in those that do, TIL-B cells represent a marked proportion of the lymphocytic infiltration. Further evaluation of T cell populations in the same samples indicate that T cell numbers remain relatively consistent but that the numbers of B-cells, especially CD79A+ B-cells, does vary from patient to patient. These data indicate that CD79A+ TIL-B cells are contributing to the generation of an efficient immune response in some but not all patients, and are greatly influencing disease survivability. This information may allow us to stratify patients into low and high risk groups based on the presence or absence of TIL-B cells, respectively. Citation Format: Sara M. Centuori, Samuel Kim, Cecil Gomes, Charles Putnam, David Mount, Linda Garland, Brandon Larsen, Jesse D. Martinez. Determining the role of tumor-infiltrating B cells in NSCLC. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 713.

Impact of Adjuvant Therapy on Patient Survival in Stage I/II High-Risk Endometrial Cancers

Impact of Adjuvant Therapy on Patient Survival in Stage I/II High-Risk Endometrial Cancers

Expression of Tiam1 predicts lymph node metastasis and poor survival of lung adenocarcinoma patients

BackgroundTo assess the value of Tiam1 in predicting lymph node metastasis and survival after curative resection in patients with lung adenocarcinoma.MethodsImmunohistochemical staining for Tiam1 was performed on 98 adenocarcinoma and 30 normal lung tissues. The association of Tiam1 protein expression with the clinicopathological characteristics and the prognosis of lung adenocarcinoma were subsequently assessed.ResultsImmunohistochemical analysis showed that 60 of 98 (61.22%) adenocarcinoma tissues showed high expression of Tiam1, and high Tiam1 expression was significantly associated with advanced TNM stage (P < 0.0005) and lymph node status (P < 0.0005) of lung adenocarcinoma. Moreover, the lung adenocarcinoma patients with low Tiam1 expression had higher overall survival than patients with high Tiam1 expression (log rank value = 10.805, P = 0.001). High expression of Tiam1 predicted poor overall survival of patients in stages I + II (P = 0.006). Furthermore, multivariate analysis indicated that high expression of Tiam1 protein was an independent prognostic factor for overall survival (P = 0.011) in patients with lung adenocarcinoma.ConclusionThese findings suggest for the first time that Tiam1 expression may be beneficial in predicting lymph node metastasis and survival of patients with lung adenocarcinoma. A future study will investigate whether Tiam1 can serve as a novel therapeutic target in lung adenocarcinoma.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1377798917111123.

P-0023 Gastric Cancer in Latvia in 1980 – 2010

ABSTRACT Introduction According to GLOBOCAN 2008 data gastric cancer currently is the fourth most common cancer worldwide and the second most common cause of cancer death. The objective of this study was to get comparable data on gastric cancer for 30 years period, to analyze the trends of incidence and mortality in Latvia and to compare with situation in other countries. Methods Incidence and mortality data from 1980 to 2010 in Latvia were obtained from the National Health Service. IARC (GLOBOCAN 2008) database was used for international comparisons. Incidence and mortality rates were age standardized to the World Standard Population and expressed per 100,000 population. Results There were 24,413 new gastric cancer cases diagnosed during the observed period, of which 55.1% (n=13,456) in male and 44.9% (n=10,957) in female. 57.4% (n=14,006) of new cases were registered in patients at age 60 – 80 years and 6.3% (n=1530) at age below 45 years. Most of all new cancer cases – 15.8% (n=3851) – were diagnosed in patients at age group 70 – 74 years. Out of all new gastric cancer cases 5.2% (n=1268) were diagnosed in stage I, 13.9% (n=3402) in stage II, 26.9% (n=6579) at stage III, and 38.9% (n=9493) at stage IV (no information regarding stage for 15.0% (n=3671) of cases). The age-standardized incidence rate (W) of gastric cancer has decreased from 26.4 per 100,000 population in 1980 to 13.3 in 2010 (in male - from 37.4 to 20.3; in female - from 19.8 to 9.0). First year’s lethality has increased from 55.1% in 1980 to 59.2% in 2010. The overall first year’s lethality for patients in stage I was 8.0%, in stage II – 25.9%, in stage III – 48.7%, and in stage IV – 84.1%. Five year observed survival has decreased from 22.3% for patients diagnosed in 1980 to 16.8% for patients diagnosed in 2005. The overall five year observed survival for patients in stage I was 71.8%, in stage II – 42.6%, in stage III – 20.3%, and in stage IV – 4.1%. The age-standardized mortality rate (W) has decreased from 20.8 per 100 000 population in 1980 to 10.7 in 2010 (in male - from 29.3 to 16.9; in female - from 15.8 to 7.1). Conclusion While the incidence and mortality rates of gastric cancer in Latvia are steady declining, the rates are considerably higher than on average in Europe or in European Union. The incidence and mortality rates based on real data are very close to or are the same as estimated rates calculated by IARC (old world standard population). While in absolute numbers the number of new cases is almost the same for both genders, the age-standardized rates shows that male are affected twice as often as females. Due to late diagnose of gastric cancer, the first year’s lethality is high with tendency to increase and the five years observed survival is low with tendency to decrease. Both improvement of early diagnostics and public health education is necessary to improve the general situation with gastric cancer in Latvia.

Extracorporeal membrane oxygenation–assisted primary percutaneous coronary intervention may improve survival of patients with acute myocardial infarction complicated by profound cardiogenic shock

PurposeThe aim of this study was to evaluate the impact of extracorporeal membrane oxygenation (ECMO) assistance on the clinical outcome of patients with acute myocardial infarction (AMI) that is complicated by profound cardiogenic shock (CS) who received primary percutaneous coronary intervention (PCI). Materials and MethodsWe collected patients from January 2004 through December 2006 (stage 1); 25 patients who presented with AMI and received primary PCI and had profound CS were enrolled in the study. Intraaortic balloon counterpulsation (IABP) was the only modality for extracorporeal support in our hospital. From January 2007 through December 2009 (stage 2), 33 patients who presented with AMI and received primary PCI and had profound CS were enrolled; for this stage; both intra-aortic balloon counter-pulsation and ECMO support were available in our facility. ResultsA Kaplan-Meier survival analysis displayed significantly improved survival for patients in stage 2 (P = .001; 1-year survival in stage 1 vs 2; 24% vs 63.64%). Patients presenting with either STEMI (ST segment elevation myocardial infarction) or NSTEMI (Non-ST segment elevation myocardial infarction) benefited from ECMO-assisted PCI (P < .05). In stage 1, patients with refractory ventricular tachycardia/ventricular fibrillation had a very low survival rate; however, in stage 2, the survival rate of patients with and without refractory ventricular tachycardia/ventricular fibrillation was similar (P = .316). ConclusionExtracorporeal membrane oxygenation–assisted PCI for patients with AMI that is complicated by profound CS may improve the 30-day and 1-year survival rates.

Expression of cysteine-rich 61 is correlated with poor prognosis in patients with esophageal squamous cell carcinoma

Introduction Cysteine-rich 61 (Cyr61), a secreted protein belonged to the CCN family, was involved in the progression of many cancers. The purpose of this study was to explore the clinical significance of Cyr61 expression in esophageal squamous cell carcinoma (ESCC). Materials and methods Cyr61 expression was detected on tissue microarrays of ESCC samples in 372 cases by using immunohistochemical staining. Survival analysis was assessed by the Kaplan–Meier analysis. Relative risk was evaluated by the multivariate Cox proportional hazards model. Results The staining pattern of Cyr61 was heterogeneous and varied from negative to intense expression in a cytoplasmic distribution. Kaplan–Meier analysis revealed that expression of Cyr61 was related to poor survival of ESCC patients ( P = 0.001). Further analysis revealed that Cyr61 high-expression was related to poorer overall survival of patients in stage I/II ( P = 0.001); but did not effect the overall survival of patients in stage III/IV. Univariate and multivariate analysis suggested that Cyr61 expression status was an independent prognostic factor for ESCC ( P = 0.001). Discussion Cyr61 might play important roles in the progression of ESCC. Cyr61 is a new biomarker to predict the prognosis of ESCC patients.

Association between statin treatment and outcome in relation to renal function in survivors of myocardial infarction

As statins are recommended at discharge to all patients following myocardial infarction (MI), we studied their use and efficacy in renal disease by analyzing the data, in the nationwide SWEDEHEART registry, of 42,814 consecutive survivors of MI with available creatinine/dialysis data but without statin therapy on admission. The estimated glomerular filtration rate (eGFR) was determined by the Modification of Diet in Renal Disease Study formula and the patients classified into the five traditional stages of kidney disease. The 1-year survival in relation to prescription of statin at discharge was assessed in a Cox regression analysis adjusted by a propensity score that described each individual's likelihood of being treated with a statin, established by 36 baseline characteristics and in-hospital therapies. Statin use at discharge decreased with increased renal impairment from 81% in eGFR stage 1 to 31% in eGFR stage 5. After adjusting for the propensity score and discharge medication, statin use was associated with a significant reduction in overall risk of death (hazard ratio 0.63), with a statistically significant interaction between statin therapy and the stage of renal function. Thus, statin use at discharge was associated with improved 1-year survival of patients in stages 2-4 (mild-to-severe) of renal insufficiency. This effect appears attenuated in those with stage 5 renal failure.

KRAS mutation, cancer recurrence, and patient survival in stage III colon cancer: Findings from CALGB 89803

4037 Purpose: KRAS mutation in stage IV colorectal cancer predicts resistance to anti-EGFR targeted treatment (cetuximab or panitumumab). However, whether the presence of KRAS mutation independently predicts the survival of colon cancer patients remains uncertain. Methods: We conducted a prospective observational study of 508 cases identified among 1264 patients with stage III colon cancer who enrolled in a randomized adjuvant chemotherapy trial (5-fluorouracil, leucovorin with or without irinotecan) between April 1999 and May 2001 (CALGB 89803; Saltz et al. J Clin Oncol 2007). KRAS mutations were detected in 178 tumors (35%) by Pyrosequencing. Kaplan-Meier and Cox proportional hazard models were used to assess the significance of KRAS mutational status and adjusted for potential confounders including age, sex, tumor location, T stage, N stage, performance status, adjuvant chemotherapy arm and microsatellite instability (MSI) status. Results: When compared to patients with wild-type KRAS, those with a mutation in KRAS did not experience any difference in disease-free (DFS), recurrence-free (RFS), or overall survival (OS) (log-rank P&gt;0.56 for DFS, RFS, and OS). Five-year DFS was 62% for KRAS-mutated and 63% for KRAS-wild-type patients. Five-year RFS was 64% for KRAS-mutated and 66% for KRAS- wild-type patients. Five-year OS was 74% for KRAS-mutated and 73% for KRAS-wild-type patients. The effect of KRAS mutation on patient survival did not differ according to clinical features, chemotherapy arm or MSI status, and the effect of adjuvant chemotherapy assignment on outcome did not differ according to KRAS status. Conclusions: In this large clinical trial of chemotherapy in patients with stage III colon cancer, KRAS mutational status was not associated with any significant influence on disease-free or overall survival. No significant financial relationships to disclose.

Claudin-1 is a strong prognostic indicator in stage II colonic cancer: a tissue microarray study

Tight junction associated proteins are key molecular components governing cellular adhesion, polarity and glandular differentiation. Tight junction proteins also play critical roles in cellular proliferation and neoplastic pathways via their functions as couplers of the extracellular milieu to intracellular signaling pathways and the cytoskeleton. Neoplastic cells frequently exhibit structural and functional deficiencies in the tight junction. The purpose of this study was to determine the pattern of expression and prognostic value of four tight junction associated proteins, claudin-1, claudin-4, occludin and ZO-1 in a cohort of TNM stage II colon cancer using tissue microarray technology. In this study, we retrospectively analyzed, resected and otherwise untreated paraffin embedded specimens from 129 consecutive patients with TNM stage II colonic carcinomas for claudin-1, claudin-4, occludin and ZO-1 protein expression by immunohistochemistry. Seventy-five, 58, 56 and 44% of the tumors exhibited normal to elevated expression levels (+2 and +3 immunopositivity) of claudin-1, claudin-4, occludin and ZO-1 respectively. Low expression levels of claudin-1 and ZO-1 were directly associated with higher tumor grade (P=0.05 and 0.03 respectively). Multivariate analysis indicated that lymphovascular invasion (P=0.01) and low levels of claudin-1 (P=0.0001) expression were independent predictors of recurrence and that reduced claudin-1 expression (P=0.0001) was associated with poor survival. This study is the first to comprehensively examine the expression of several tight junction associated proteins in colonic neoplasms and to correlate their expression with disease progression. Loss of claudin-1 expression proved to be a strong predictor of disease recurrence and poor patient survival in stage II colon cancer.

MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer.

Early-stage non-small cell lung cancer (NSCLC) can be cured by surgical resection, but a substantial fraction of patients ultimately dies due to distant metastasis. In this study, we used subtractive hybridization to identify gene expression differences in stage I NSCLC tumors that either did or did not metastasize in the course of disease. Individual clones (n=225) were sequenced and quantitative RT-PCR verified overexpression in metastasizing samples. Several of the identified genes (eIF4A1, thymosin beta4 and a novel transcript named MALAT-1) were demonstrated to be significantly associated with metastasis in NSCLC patients (n=70). The genes' association with metastasis was stage- and histology specific. The Kaplan-Meier analyses identified MALAT-1 and thymosin beta4 as prognostic parameters for patient survival in stage I NSCLC. The novel MALAT-1 transcript is a noncoding RNA of more than 8000 nt expressed from chromosome 11q13. It is highly expressed in lung, pancreas and other healthy organs as well as in NSCLC. MALAT-1 expressed sequences are conserved across several species indicating its potentially important function. Taken together, these data contribute to the identification of early-stage NSCLC patients that are at high risk to develop metastasis. The identification of MALAT-1 emphasizes the potential role of noncoding RNAs in human cancer.

Large cell neuroendocrine carcinoma and large cell carcinomas with neuroendocrine morphology of the lung: prognosis after complete resection and systematic nodal dissection

Background Large cell neuroendocrine carcinoma (LCNEC) and large cell carcinoma with neuroendocrine morphology of the lung are both currently classified as subtypes of large cell carcinomas according to the World Health Organization IASLC classification system for lung and pleural tumors. Prognosis is reported as similar to that of small cell carcinomas. There is no consensus on management of this subset and adjuvant chemotherapy is recommended by some for early stage LCNEC to impact long-term prognosis. We retrospectively reviewed a cohort of patients at our institution who had this type of tumor to determine factors that might influence survival. Methods Twenty-one cases of LCNEC and large cell carcinoma with neuroendocrine morphology were identified in the files of the Royal Brompton Hospital between 1986 and 1999. All patient data were reviewed, and complete follow-up was achieved with 20 of these patients. Results Of the 21 patients identified, 20 underwent resection with systematic nodal dissection in 18. There was no in-hospital mortality. Of those patients fully staged by systematic nodal dissection, 9 were stage I, 5 were stage II and 4 were stage III. Median follow-up was 25 months (range, 2 to 120 months). At the time of review, 11 patients were alive and free of disease. One patient was alive and free of disease when lost to follow-up. Nine patients had died, 7 related and 2 unrelated to disease. The 5-year actuarial survival for the entire group was 47%. The actuarial survival of accurately staged, stage I patients at 5 years was 88%. The actuarial survival of patients in stage II and III was 28% at 5 years. Conclusions LCNEC and large cell carcinoma with neuroendocrine morphology are aggressive tumors, but patients with completely resected disease after systematic nodal dissection have a better prognosis than previously described. Patients with more advanced disease have a poor prognosis.

Lung Cancer Treated Surgically in Patients

Some investigators have suggested that lung cancer in young patients has a more aggressive course and a poorer prognosis than lung cancer in older patients. The aim of this study was to determine if the basal characteristics and survival in younger patients with lung cancer undergoing surgical resection differ from those of older patients. Retrospective clinical study. Of 1,208 consecutive patients who underwent surgery for primary lung cancer between June 1984 and March 2000, we reviewed the medical records of 110 younger patients who were < 50 years of age at the time of surgery and compared them with 1,098 older patients (> or = 50 years of age). All deaths were included. In the younger patient group, asymptomatic disease and adenocarcinoma was significantly more frequent, the rate of smoking was significantly higher, and the amount of smoking (Brinkman index) was significantly larger. For the 94 younger patients with complete resection, the 5-year survival rate was 61.0%, which was not significantly higher than that for the 923 older patients (57.7%). However, the 53 younger patients with stage I disease (5-year survival of 84.3%) had significantly better survival than older patients with the same condition (71.6%). Survival of patients in stage II or stage III disease was not significantly different. The younger patients had significantly better prognoses, and a statistical difference was shown especially in the early stage, while in the advanced stage the malignancy of the lung cancer itself surpassed the difference in survival.