Global models underestimate large decadal declining and rising water storage trends relative to GRACE satellite data.

Assessing reliability of global models is critical because of increasing reliance on these models to address past and projected future climate and human stresses on global water resources. Here, we evaluate model reliability based on a comprehensive comparison of decadal trends (2002-2014) in land water storage from seven global models (WGHM, PCR-GLOBWB, GLDAS NOAH, MOSAIC, VIC, CLM, and CLSM) to trends from three Gravity Recovery and Climate Experiment (GRACE) satellite solutions in 186 river basins (∼60% of global land area). Medians of modeled basin water storage trends greatly underestimate GRACE-derived large decreasing (≤-0.5 km3/y) and increasing (≥0.5 km3/y) trends. Decreasing trends from GRACE are mostly related to human use (irrigation) and climate variations, whereas increasing trends reflect climate variations. For example, in the Amazon, GRACE estimates a large increasing trend of ∼43 km3/y, whereas most models estimate decreasing trends (-71 to 11 km3/y). Land water storage trends, summed over all basins, are positive for GRACE (∼71-82 km3/y) but negative for models (-450 to -12 km3/y), contributing opposing trends to global mean sea level change. Impacts of climate forcing on decadal land water storage trends exceed those of modeled human intervention by about a factor of 2. The model-GRACE comparison highlights potential areas of future model development, particularly simulated water storage. The inability of models to capture large decadal water storage trends based on GRACE indicates that model projections of climate and human-induced water storage changes may be underestimated.

Understanding of Contemporary Regional Sea-Level Change and the Implications for the Future.

Global sea level provides an important indicator of the state of the warming climate, but changes in regional sea level are most relevant for coastal communities around the world. With improvements to the sea-level observing system, the knowledge of regional sea-level change has advanced dramatically in recent years. Satellite measurements coupled with in situ observations have allowed for comprehensive study and improved understanding of the diverse set of drivers that lead to variations in sea level in space and time. Despite the advances, gaps in the understanding of contemporary sea-level change remain and inhibit the ability to predict how the relevant processes may lead to future change. These gaps arise in part due to the complexity of the linkages between the drivers of sea-level change. Here we review the individual processes which lead to sea-level change and then describe how they combine and vary regionally. The intent of the paper is to provide an overview of the current state of understanding of the processes that cause regional sea-level change and to identify and discuss limitations and uncertainty in our understanding of these processes. Areas where the lack of understanding or gaps in knowledge inhibit the ability to provide the needed information for comprehensive planning efforts are of particular focus. Finally, a goal of this paper is to highlight the role of the expanded sea-level observation network-particularly as related to satellite observations-in the improved scientific understanding of the contributors to regional sea-level change.

Feline mammary basal-like adenocarcinomas: a potential model for human triple-negative breast cancer (TNBC) with basal-like subtype.

BACKGROUND: Breast cancer is one of the leading causes of cancer deaths. Triple-negative breast cancer (TNBC), an immunophenotype defined by the absence of immunolabeling for estrogen receptor (ER), progesterone receptor (PR) and HER2 protein, has a highly aggressive behavior. A subpopulation of TNBCs exhibit a basal-like morphology with immunohistochemical positivity for cytokeratins 5/6 (CK5/6) and/or epidermal growth factor receptor (EGFR), and have a high incidence of BRCA (breast cancer susceptibility) mutations. Feline mammary adenocarcinomas (FMAs) are highly malignant and share a similar basal-like subtype. The purpose of this study was to classify FMAs according to the current human classification of breast cancer that includes evaluation of ER, PR and HER2 status and expression of basal CK 5/6 and EGFR. Furthermore, we selected triple negative, basal-like FMAs to screen for BRCA mutations similar to those described in human TNBC. METHODS: Twenty four FMAs were classified according to the current human histologic breast cancer classification including immunohistochemistry (IHC) for ER, PR HER2, CK5/6 and EGFR. Genetic alteration and loss of heterozygosity of BRCA1 and BRCA2 genes were analyzed in triple negative, basal-like FMAs. RESULTS: IHC for ER, PR and HER2 identified 14 of the 24 (58%) FMAs as a triple negative. Furthermore, 11 of these 14 (79%) triple negative FMAs had a basal-like subtype. However, no genetic abnormalities were detected in BRCA1 and BRCA2 by direct sequencing and loss of heterozygosity analysis. CONCLUSION: FMAs are highly aggressive neoplasms that are commonly triple negative and exhibit a basal-like morphology. This is similar to human TNBC that are also commonly classified as a basal-like subtype. While sequencing of a select number of triple negative, basal-like FMAs and testing for loss of heterozygosity of BRCA1 and BRCA2 did not identify mutations similar to those described in human TNBC, further in-depth evaluation is required to elucidate a potential role of BRCA in the tumorigenesis of triple negative, basal-like FMAs. The strong similarities in clinical behavior, morphology and IHC phenotype suggest that triple negative, basal-like FMAs may be a suitable spontaneous animal model for studying novel therapeutic approaches against human basal-like TNBC.

The role of sentinel lymph node mapping in colon cancer: detection of micro-metastasis, effect on survival, and driver of a paradigm shift in extent of colon resection.

Unlike in breast cancer and melanoma, sentinel lymph node mapping in colon cancer is primarily used as an aid to the pathologist for accurate nodal staging. The study was undertaken to review the incidence of micro-metastasis and its impact on survival when treated with chemotherapy. The study was also undertaken to see if SLNM could guide limited colon resection in early T stage tumor as a paradigm shift. SLNM was done by subserosal injection of a blue dye. SLNs were ultra-staged by multilevel sectioning and remaining Specimen was then examined by conventional method. For the last 245 patients the specimen was divied ex vivo into two segments as segment A containing the tumor bearing portion of the colon and SLNs with attached mesentery, while segment B include distal part of the colon with attached mesentery. Nodal staging was separately examined. Of the 354 Pts, SLNM was successful in 99.9% of Pts with an average no of SLN/ Pt = 2.8 and total nodes 17.8/pt. Survival was directly related negatively with stage and nodal status. Pts with +ve LN did much better with chemotherapy than without chemotherapy. With 245 Pts, specimen A Vs B, no Pts had +ve node in specimen B with -ve LN in specimen A. SLNM results in more node/Pt, more positive node/Pt ,and more micro-metastasis who when treated with chemotherapy survive longer. Limited segmental resection in early T stage is possible when done with guidance by SLNM without compromising biology.

Groundwater depletion in California's Central Valley accelerates during megadrought.

Groundwater provides nearly half of irrigation water supply, and it enables resilience during drought, but in many regions of the world, it remains poorly, if at all managed. In heavily agricultural regions like California's Central Valley, where groundwater management is being slowly implemented over a 27-year period that began in 2015, groundwater provides two-thirds or more of irrigation water during drought, which has led to falling water tables, drying wells, subsiding land, and its long-term disappearance. Here we use nearly two decades of observations from NASA's GRACE satellite missions and show that the rate of groundwater depletion in the Central Valley has been accelerating since 2003 (1.86 km3/yr, 1961-2021; 2.41 km3/yr, 2003-2021; 8.58 km3/yr, 2019-2021), a period of megadrought in southwestern North America. Results suggest the need for expedited implementation of groundwater management in the Central Valley to ensure its availability during the increasingly intense droughts of the future.

Detection and prognostic impact of micrometastasis in colorectal cancer.

Review of literature was performed on studies with prognostic impact of micrometastasis in colorectal cancer. Among 16 studies included, micrometastasis was detected in 26.5% of patients. Most analysis revealed that micrometastasis carries a poorer prognosis compared to node negative disease (NND). The results of those studies were compared with our pilot study of 109 patients with colon cancer, showing improved prognosis of micrometastasis after being upstaged and treated with chemotherapy when compared with NND.

Comparative analysis of bone marrow micrometastases with sentinel lymph node status in early-stage breast cancer.

Bone marrow micrometastases (BMM) and sentinel lymph node (SLN) status are both prognostic factors in breast cancer (BRCa) patients (pts). A definitive relationship between the two has not yet been proven and the data available is controversial. Thus, a retrospective study was conducted to determine the relationship of BM status and SLN status in pts with early BRCa (T1/T2). All female pts with early BRCa (T1/T2) operated upon by a single surgeon were included in the study. Prior to surgery, all pts underwent bone marrow aspiration from the posterior superior iliac spine bilaterally. Subsequently, pts underwent SLN biopsy and definitive primary breast surgery. BM samples were examined by using a Cytokeratin Detection Kit using CAM 5.2 monoclonal antibody. All pts with BMM underwent repeat BM analysis 6 months after completing all treatments. Data was collected for SLN, BM, estrogen receptor/progesterone receptor (ER/PR), and human epidermal growth factor receptor 2 (Her-2/neu) status and analyzed using chi-square (chi (2)) analysis or Fischer's exact test. A total of 270 consecutive pts with early BRCa were studied. SLN mapping was successful in all pts. SLN metastases (mets) were detected in 28.9% (78/270) pts. Of the 270 pts, 77.0% (208/270) had T1 disease. BMM were detected in 9.6% (26/270) pts, of whom 69.2% (18/26) were found to have BMM unilaterally. BMM were detected in 11.5% (9/78) pts with SLN mets versus 8.9% (17/192) in pts with node-negative disease (p = 0.65). Of the pts with T1 BRCa, BMM were observed in 9.1% (19/208) pts versus 11.3% (7/62) in pts with T2 BRCa (p = 0.6). In pts with ER/PR-negative (-ve) BRCa, BMM were found in 7.7% (2/26) pts versus 9.9% (24/242) in pts with ER/PR-positive (+ve) BRCa (p = 0.27). BMM were detected in 12.3% (9/73) pts with Her-2/neu +ve BRCa and in 8.6% (16/187) pts with Her-2/neu -ve BRCa (p = 0.11). After completion of adjuvant therapy all pts with BMM (n = 26) converted to BM negative status. We conclude that BM status did not correlate with SLN status and occurs independently of lymphatic metastasis possibly through a different mechanism. BMM occur in node-negative pts and may assist in identifying pts at high risk for disease recurrence. Obtaining bone marrow aspirate from two locations resulted in a significant increase in detection of micrometastases.

A prospective trial comparing 1% lymphazurin vs 1% methylene blue in sentinel lymph node mapping of gastrointestinal tumors.

BACKGROUND: Methylene blue (M), as a dye in sentinel lymph node mapping (SLNM), has been introduced as an alternative to lymphazurin (L) after the recent shortage of L. M has been evaluated in breast cancer in multiple studies with favorable results. Our study compares L with M in the SLNM of gastrointestinal (GI) tumors. METHODS: Between Jan 2005 and Aug 2008, 122 consecutive patients with GI tumors were enrolled. All patients (pts) underwent SLNM with either L or M by subserosal injection of 2-5 mL of dye. Efficacy and rates of adverse reactions were compared between the two dyes. Patients were prospectively monitored for adverse reactions including anaphylaxis, development of blue hives, and tissue necrosis. RESULTS: Of 122 pts, 60 (49.2%) underwent SLNM using L and 62 (50.8%) underwent SLNM using M. Colon cancer (CrCa) was the most common site in both groups. The success rate of L and M in SLNM was 96.6% and 96.7%, respectively, with similar numbers of total number of lymph nodes per pt, SLNs per pt (<3), nodal positivity, skip metastasis, and accuracy. The only adverse reaction in the L group was oxygen desaturation >5% in 5% (3/60) of pts, compared with none in the M group. Cost per vial of L was $210 vs $7 for M. CONCLUSION: The success rate, nodal positivity, average SLNs per patient, and overall accuracy were similar between L and M. Absence of anaphylaxis and lower cost make M more desirable than L in SLNM of GI tumors.

Sentinel node biopsy for the individualization of surgical strategy for cure of early-stage colon cancer.

INTRODUCTION: The requirement for nodal analysis currently confounds the oncological propriety of focused purely endoscopic resection for early-stage colon cancer and complicates the evolution of innovative alternatives such as natural orifice transluminal endoscopic surgery (NOTES) and its hybrids. Adjunctive sentinel node biopsy (SNB) deserves consideration as a means of addressing this shortfall. METHODS: Data from two prospectively maintained databases established for multicentric studies of SNB in colon cancer that employed similar methodologies were pooled to establish technique potency selectively in T1/T2 disease (both overall and under optimized conditions) and to project potential clinical impact. RESULTS: Of 891 patients with T1-4, M0 intraperitoneal colon cancer, 225 had T1/T2 disease. Sentinel nodes were either not found or were falsely negative in 18 patients with T1/T2 cancers (8%) as compared with 17% (112/646) in those with T3/T4 disease (P = 0.001). Negative predictive value (NPV) in the former exceeded 95%, while sensitivity [including immunohistochemistry (IHC)] was 81%. In the 193 patients with T1/T2 disease recruited from those centers contributing >22 patients, sensitivity was 89% and NPV 97%. Thus, in this cohort, SNB could have correctly prompted localized resection (obviating en bloc mesenteric dissection) in 75% (144) of patients, including 59 with T1 lesions potentially amenable to intraluminal resection alone as their definitive treatment. Forty-four patients (23.4%) would still have conventional resection, leaving three patients (1.6% overall) understaged (11% false-negative rate). CONCLUSION: These findings support the further investigation of SNB as oncological augment for localized resective techniques. Specific prospective study should pursue this goal.

Prognostic relevance of occult nodal micrometastases and circulating tumor cells in colorectal cancer in a prospective multicenter trial.

PURPOSE: Nodal micrometastasis and circulating tumor cells detected by multimarker quantitative real-time reverse transcription-PCR (qRT-PCR) may have prognostic importance in patients with colorectal cancer. EXPERIMENTAL DESIGN: Paraffin-embedded sentinel lymph nodes from 67 patients and blood from 34 of these patients were evaluated in a prospective multicenter trial of sentinel lymph node mapping in colorectal cancer. Sentinel lymph nodes were examined by H&E staining and cytokeratin immunohistochemistry. Sentinel lymph nodes and blood were examined by a four-marker qRT-PCR assay (c-MET, melanoma antigen gene-A3 family, beta1-->4-N-acetylgalactosaminyltransferase, and cytokeratin-20); qRT-PCR results were correlated with disease stage and outcome. RESULTS: In H&E-negative sentinel lymph node patients that recurred, cytokeratin immunohistochemistry and qRT-PCR detected metastasis in 30% and 60% of patients, respectively. Disease-free survival differed significantly by multimarker qRT-PCR upstaged sentinel lymph node (P = 0.014). qRT-PCR analysis of blood for circulating tumor cells correlated with overall survival (P = 0.040). CONCLUSION: Molecular assessment for micrometastasis in sentinel lymph node and blood specimens may help identify patients at high risk for recurrent colorectal cancer, who could benefit from adjuvant therapy.

Short-term trends in Africa's freshwater resources: Rates and drivers.

The freshwater resources in Africa are vulnerable to natural variabilities as well as anthropogenic interventions. In this study, temporal (April 2002-June 2017) Gravity Recovery and Climate Experiment (GRACE) data are integrated, in a geographic information system environment, with rainfall, temperature, evapotranspiration, and altimetry remote sensing datasets to monitor the short-term trends in terrestrial water storage (TWS) over the African hydrogeologic systems and to explore their origins. Results show that short-term trends over the African continent are largely driven by natural variability such as changes in rainfall, evapotranspiration, and associated variations in lake levels. Exceptions to this observation include central Africa, where deforestation is found to additionally drive changes in TWS, as well as northern Africa, where TWS changes are dominated by anthropogenic groundwater extraction from fossil aquifers. Findings highlight the need for integrative responses at local, national, regional, and international levels by the African nations to overcome current and future challenges related to freshwater availability in Africa.

Contributions of GRACE to understanding climate change.

Time-resolved satellite gravimetry has revolutionized understanding of mass transport in the Earth system. Since 2002, the Gravity Recovery and Climate Experiment (GRACE) has enabled monitoring of the terrestrial water cycle, ice sheet and glacier mass balance, sea level change and ocean bottom pressure variations and understanding responses to changes in the global climate system. Initially a pioneering experiment of geodesy, the time-variable observations have matured into reliable mass transport products, allowing assessment and forecast of a number of important climate trends and improve service applications such as the U.S. Drought Monitor. With the successful launch of the GRACE Follow-On mission, a multi decadal record of mass variability in the Earth system is within reach.

Challenging the conventional treatment of colon cancer by sentinel lymph node mapping and its role of detecting micrometastases for adjuvant chemotherapy.

All colon cancer patients with lymph node (LN) positive disease are treated with chemotherapy. Patients with node negative disease are usually cured by surgery alone. Yet about 20% of patients develop recurrence within 5 years despite node negative status. This may often be the result of missed micrometastases by conventional examination. Sentinel lymph node (SLN) mapping was developed to find those nodes detected by blue dye which was ultrastaged to detect micrometastases. Consecutive patients, underwent SLN mapping with the blue dye with success rate of 99.2%. Average number of LN was 18.3, average number of SLN was 3/patient and overall nodal positivity was 45%. Ten patients had skip metastases. Overall survival of 235 patients was 84 months with survival of node negative patients 97 months versus 68 months for node positive patients. For stage I-IV patients, overall survival was as follows: stage I-115 months, stage II-90 months, stage III-84 months and stage IV-24 months respectively. Patients with micrometastases after chemotherapy had average survival of 108 months versus those without chemotherapy was 50 months. Thus, SLN mapping techniques is highly successful, easily reproducible and finds micrmoetastases in over 15% of patients which could have been missed by conventional pathological examination. These patients when treated with adjuvant chemotherapy have similar survival as those of node negative disease. Similarly, patients without any nodal metastases after SLN mapping and ultrastaging, may be considered as true node negative disease and may avoid further adjuvant chemotherapy.

Toll-like receptor expression in human non-small cell lung carcinoma: potential prognostic indicators of disease.

INTRODUCTION: Lung cancer remains the highest cause of cancer mortality worldwide. Toll-like receptors (TLR) are innate immune receptors that have both pro- and anti-tumorigenic properties. Based on findings from epidemiological studies and in rodents, we hypothesized that elevated TLR expression would be a positive prognostic indicator of disease in non-small cell lung carcinoma patients. RESULTS: Higher mRNA expression of TLR1-3 and 5-8 were significantly associated with increased overall survival (OS) when analyzed individually or as a group in both non-small cell lung carcinoma (NSCLC) patients and in the adenocarcinoma (ADC) subtype. Significant co-expression of many TLR combinations in ADC patients were also observed via RNA sequencing. Immunostaining demonstrated TLR4 and 8 significantly correlated in tumor tissue, similar to RNA. METHODS: We used kmplot.com to perform a meta-analysis on mRNA expression of TLR1-10 to determine any significant associations with OS in NSCLC and the ADC subtype. cBioportal was also used simultaneously to assess co-expression in TLR1-10 in ADC patients via RNA sequencing and to identify any molecular alterations. Lastly, immunostaining for a subset of TLRs was conducted on ADC patients. CONCLUSIONS: Expression of innate immune receptors TLR1-10 is associated with improved survival outcomes in NSCLC. Thus, further evaluation of their predictive capacity and therapeutic utility is warranted.

Prospective multicenter trial of staging adequacy in colon cancer: preliminary results.

HYPOTHESIS: Lymph node evaluation is an important prognostic factor in colorectal cancer (CRC). A 25% recurrence rate in patients with node-negative CRC suggests that current staging practices are inadequate. Focused analysis of the sentinel node (SN) by multiple sectioning and immunohistochemistry improves staging accuracy. DESIGN: Prospective phase 2 multicenter trial. SETTING: Tertiary referral cancer centers. PATIENTS: Between March 2001 and June 2005, 132 patients were enrolled with clinical stage I and II CRC in a prospective multicenter trial (R01-CA90484). INTERVENTION: During a standard oncologic resection, lymphatic mapping was performed and the SN identified either by the surgeon or the pathologist. Hematoxylin-eosin staining was performed on all lymph nodes and immunohistochemistry, on lymph nodes negative by hematoxylin-eosin staining. MAIN OUTCOME MEASURES: Micrometastases greater than 0.2 mm but less than 2 mm and isolated tumor cells less than 0.2 mm were defined according to the sixth edition of the American Joint Committee on Cancer Cancer Staging Manual. RESULTS: The 63 men and 69 women had a median age of 74 years. Sixty-eight patients (52%) underwent a right hemicolectomy; 3 (2.3%), a transverse colectomy; 9 (7%), a left colectomy; 15 (11%), a sigmoid colectomy; 34 (26%), a low anterior resection; 1 (1%), an abdominal perineal resection; and 2 (2%), a total colectomy. Of the 111 evaluable primary tumors, 19 (17%) were T1 lesions; 17 (15%), T2; 72 (65%), T3; and 3 (2.7%), T4 tumors. Thirty-three patients (30%) were classified as stage I; 46 (41%), stage II, and 32 (29%), stage III. The SN was identified by the surgeon in 127 patients (96%) and by the pathologist in 5 patients (4%). The median number of SNs and total lymph nodes examined were 3 and 14.5, respectively. The sensitivity of lymphatic mapping and SN analysis was 88.2% and the false-negative rate, 7.4% (6/81). Of the 6 false-negative results, 4 were attributed to lymphatic channels obliterated by tumor. Upstaging occurred in 28 patients (23.6%). CONCLUSIONS: In a multicenter trial, ultrastaging of colon cancer is feasible and accurate. In stage II CRC, 24% of patients had nodal carcinoma cells not detected by conventional staging methods. Surgical technique (adequate lymph node retrieval) and focused pathological analysis may improve staging accuracy and the selection of patients for chemotherapy. The unnecessary toxicity and expense of chemotherapy may be avoided in those patients who are truly node negative.

A multicenter trial of sentinel lymph node mapping in colorectal cancer: prognostic implications for nodal staging and recurrence.

BACKGROUND: Sentinel lymph node (SLN) mapping (M) for staging in colorectal cancer (CRCa) remains controversial and needs to be validated. This study analyzes results of SLNM at a multi-institutional level for CRCa. METHODS: Group A patients underwent SLNM with 1 to 3 mL of 1% lymphazurin. First 1 to 4 blue lymph nodes were designated as SLNs and had focused analysis. Group B had standard resection and nodal staging. Patients with a minimum of 2 years of follow-up were analyzed for recurrence. RESULTS: Overall nodal metastasis were 50% for 500 group A patients versus 35% for 368 group B patients. In SLNM patients success, accuracy, sensitivity, and negative predictability values were 98%, 96%, 90%, and 93%, respectively. With a 2-year minimum follow-up, 153 group A patients had 7% recurrences compared with 25% in 162 group B patients. CONCLUSION: SLNM is highly feasible and accurate for staging CRCa with higher detection of nodal metastasis and lower recurrences.

Sentinel lymph node mapping in colon and rectal cancer: its impact on staging, limitations, and pitfalls.

Sentinel lymph node (SLN) mapping has been widely applied in the staging of solid neoplasms including colon and rectal cancer. Since the first reported feasibility study in 1997, there have been numerous publications validating SLN mapping as a highly accurate and powerful upstaging technique for colon and rectal cancer. In addition to refining the technical aspects of this procedure, these studies have investigated the use of other tracers and operative techniques, while determining the indications, limitations, and pitfalls of SLN mapping in patients with colorectal cancers. This chapter reviews the rationale for performing SLN mapping for the accurate staging of colon and rectal cancers, and provides a brief review of the historical background of the development of the procedure. Landmark publications, which have contributed to the current status of the technique, are discussed. We will focus on the technical details of the procedure, and on the pathological evaluation of the specimen and the SLNs. The various tracers and techniques of SLN mapping in colon and rectal cancer will be discussed. We have performed SLN mapping in more than 240 consecutive patients over the past 7 years. The success rates for identifying at least one SLN for colon and rectal cancer were 100% and 90.6%, respectively. The accuracy rates were 95.8% and 100%, respectively. In terms of upstaging, 32.3% of colon cancer patients with nodal metastases and 16.7% of rectal patients with nodal metastases were upstaged by the detection of micrometastases found in the SLNs only. Finally, we will also discuss the current role as well as the future research directions for SLN mapping in colon and rectal cancer.

c-MET expression level in primary colon cancer: a predictor of tumor invasion and lymph node metastases.

PURPOSE: Both c-MET and vascular endothelial growth factor (VEGF)-C expression are important factors in primary carcinoma progression. We hypothesized that overexpression of c-MET and/or VEGF-C mRNA in primary colorectal cancer (CRC) can predict tumor invasion and regional metastasis. EXPERIMENTAL DESIGN: The level of c-MET and VEGF-C mRNA expression was assessed using a quantitative RT-RealTime PCR assay on early stage primary CRC tumors (n = 36). RESULTS: The c-MET mRNA copy number ranged from 1.18 x 10(2) to 1.11 x 10(6) copies (median 5.17 x 10(4)) per 250 ng of RNA from CRC specimens. c-MET mRNA copies in CRC specimens was significantly higher than that from normal colon mucosal epithelium (P = 0.0001). c-MET mRNA copies significantly correlated with the depth of invasion: T(1) versus T(2), P = 0.007; T(1) versus T(3)/T(4), P = 0.0001; T(1) versus T(2) versus T(3)/T(4), P = 0.0005; and T(1)/T(2) versus T(3)/T(4), P = 0.011. c-MET copy number in primary CRC of N(1)/N(2) staged patients was significantly higher than N(0) cases (P < 0.03). Expression levels of c-MET mRNA were verified with immunohistochemistry analysis of c-MET protein expression in CRC specimens and normal mucosal epithelium. The VEGF-C mRNA copies of primary CRC assessed ranged from 0 to 1.65 x 10(5) copies (median 580). Although VEGF-C mRNA copies in CRC primary tumors were significantly higher than normal colon mucosal epithelium (P = 0.0008), it did not correlate with any major clinicopathological parameters of CRC. CONCLUSIONS: This study indicates c-MET mRNA overexpression in primary CRC may be an important prognostic marker for early stage invasion and regional disease metastasis.

The prognostic value of additional malignant lesions detected by magnetic resonance imaging versus mammography.

BACKGROUND: Nodal positivity is correlated with a poorer prognosis in breast cancer. A study was composed to compare nodal positivity in patients with single versus multiple lesions found on magnetic resonance imaging (MRI) and mammogram (MMG). METHODS: A retrospective study of breast cancer patients undergoing MRI and MMG was performed. Nodal positivity was compared in patients with additional invasive lesions found on MRI versus single invasive lesions found on MRI and MMG. RESULTS: A total of 425 patients were included. The overall nodal positivity was 23.8%. Patients with single versus multiple malignant lesions had nodal positivity of 20.9% vs 31.1% (P = .04). MRI detected multiple lesions in 120 patients, 80 of which were not detected by MMG (18.8%). Comparing single lesions with additional malignant lesions detected by MRI only, nodal positivity increased from 20.9% to 51.6% (P = .0002). CONCLUSIONS: Patients with additional invasive lesions on MRI had significantly higher nodal positivity than single invasive lesions. Hence, addition of MRI in early-stage breast cancer may have prognostic value because of detection of potential node-positive patients.

Tumor size predicts long-term survival in colon cancer: an analysis of the National Cancer Data Base.

BACKGROUND: American Joint Committee on Cancer uses tumor size for "T" staging of many solid tumors for its effect on prognosis. However, tumor size has not been incorporated in tumor (T), nodal status (N), metastasis (M) staging for colon cancer. Hence, the National Cancer Data Base was used to determine whether tumor size correlates with TNM staging and survival. METHODS: For the 300,386 patients, tumor size was divided into S1 (0 to 2 cm), S2 (>2 to 4 cm), S3 (>4 to 6 cm), and S4 (>6 cm). Statistical comparison was done for TNM stage, grade, and nodal status with tumor size. Kaplan-Meier survival analysis was done for each "S" stage. RESULTS: Of the 300,386 patients, 13% were classified as S1, 39% S2, 30% S3 and 18% as S4. Right colon was the most common site (48%). Tumor size positively correlated with grade, T stage, and nodal stage. Tumor size was inversely associated with survival. CONCLUSION: Tumor size is positively correlated with important prognostic factors and negatively impacted survival.