Expression of MMP-9 and WAVE3 in colorectal cancer and its relationship to clinicopathological features

Purpose

To investigate matrix metalloproteinase 9 (MMP-9) and WAVE3 expression in human colorectal cancer (CRC) and to evaluate their clinical significance.

Methods

We first performed real-time PCR to evaluate mRNA expression of MMP-9 and WAVE3 in 21 pairs of fresh CRC samples matched with adjacent normal mucosa. Then, MMP-9 and WAVE3 proteins were evaluated by immunohistochemistry on CRC tissue microarrays which included 216 CRC specimens and corresponding normal colorectal mucosa, and their correlation with clinicopathological factors and overall survival after surgery was evaluated.

Results

Both real-time PCR and immunohistochemistry evaluation have demonstrated that MMP-9 and WAVE3 were over-expressed in colorectal cancer tissues compared with normal mucosa (p?<?0.001). MMP-9 expression was significantly higher in patients with low-grade differentiation and distant metastasis (p?=?0.003 and p?=?0.005, respectively), and patients with MMP-9-positive expression had a poorer prognosis (p?=?0.008). However, patients with WAVE3-positive expression had a better prognosis (p?=?0.039) and particularly favorable prognostic factors, including non-lymph node metastasis, non-distant metastasis, and early TNM stage (p?=?0.029, 0.021, and 0.003, respectively). In addition, MMP-9-negative/WAVE3-positive patients had the best overall survival (p?=?0.021). In multivariate survival analysis, MMP-9 expression and combined expression status of MMP-9/WAVE3 were identified as independent prognostic factors for CRC (p?=?0.046 and p?=?0.019, respectively).

Conclusions

Combined analysis of MMP-9 and WAVE3 has a significant value for assessing prognosis of CRC patients after surgery.     

Hepatic steatosis is associated with lower incidence of liver metastasis from colorectal cancer

Purpose

Both hepatic steatosis (HS) and colorectal cancer (CRC) are conditions associated with metabolic syndrome. The liver is the most frequent site of distant metastasis of CRC; however, the impact of HS on the incidence of liver metastasis of CRC is not clearly defined. Then, the correlation with the presence or absence of HS was analyzed.

Methods

A total of 604 CRC patients receiving curative surgical resection who had a preoperative non-enhanced computed tomography (CT) were enrolled. The mean attenuation values (in Hounsfield units) of the liver and spleen were obtained on a plain CT slice, and the patients with liver–spleen attenuation ratio lower than 1.1 were objectively defined as HS. The clinicopathological features of these patients were analyzed, and the association between HS and the clinical features of CRC was examined.

Results

Sixty-three (10.4 %) among the 604 patients were diagnosed as HS. Recurrence-free survival (RFS) and hepatic RFS, but not extrahepatic RFS, were significantly higher in the group with HS (p?=?0.04 and p?=?0.006). However, this effect was not evident in the group of patients with obesity, defined as body mass index?>?25.0. Among the stage I~III cases, HS was significantly associated with lower hepatic, but not extrahepatic, RFS. Moreover, absence of HS was an independent risk factor for hepatic RFS (p?=?0.003).

Conclusion

Metastases of CRC are less frequent in fatty liver. Steatosis may be an unfavorable microenvironment for metastatic formation in the liver.     

Association study identifying polymorphisms in CD47 and other extracellular matrix pathway genes as putative prognostic markers for colorectal cancer

Purpose

We identified recently the extracellular matrix (ECM) receptor interaction pathway as a consistently overrepresented category among gene expression profiling studies on colorectal cancer (CRC) prognosis.

Methods

Putative regulatory single nucleotide polymorphisms (SNPs) in genes from the ECM pathway were genotyped in 613 CRC patients from Northern Germany (PopGen cohort) and tested for association with disease progression and survival.

Results

The eSNP (SNP associated with expression) rs12695175 in CD47 associated with CRC specific survival (HR?=?2.18, 95 % CI 1.10–4.33, CC versus AA) and with overall survival (HR?=?1.99, 95 % CI 1.04–3.81, CC versus AA). This association remained significant after adjustment for age at diagnosis, tumour stage (T) and lymph node status (N). Three polymorphisms in CD47 were associated with distant metastasis in a dominant model: rs9879947 and rs3206652 in the 3′-UTR (OR?=?1.64, 95 % CI 1.01–2.64 and OR?=?1.88, 95 % CI 1.27–2.80, respectively) and the eSNP rs3804639 (OR?=?1.73, 95 % CI 1.17–2.57).

Conclusions

The novel associations of eSNPs in CD47 with worse survival and distant metastasis should be confirmed by additional studies, since increased expression of this gene has recently been shown to be an indicator of poor prognosis in cancer patients.     

Elevated circulating levels of tissue factor-positive microvesicles are associated with distant metastasis in lung cancer

Purpose

Microvesicles (MV) in the blood stream are associated with distant metastasis in cancer. Platelet or endothelial cell-related MV actively participate in thrombogenesis, which is an important step in cancer metastasis. This study investigated the correlations between MV levels of platelet-poor plasma and distant metastasis in lung cancer.

Methods

Platelet-poor plasma from 44 treatment-naive lung cancer (23 with distant metastasis) and 19 normal subjects was used to determine the levels of glycoprotein Iβ (CD42) + platelet MV (PMV), P-selectin (CD62P) + PMV, VE-cadherin (CD144) + endothelial MV (EMV), tissue factor (CD142) + MV, thrombin-antithrombin complex and vascular endothelial growth factor (VEGF).

Results

The level of CD142 + MV was significant (odds ratio 5.86, 95 % confidence interval 1.31–38.3) in predicting distant metastasis in lung cancer, and a cutoff value of 2.668 (after logarithm transformation) in the ROC curve had a specificity of 90 % and a sensitivity of 59 %. The presence of distant metastasis showed a significant correlation between CD144 + EMV and VEGF, but not between CD144 + EMV and CD42 + PMV or CD62P + PMV in lung cancer subjects.

Conclusions

The finding of CD142 + MV in platelet-poor plasma may be useful for suggesting distant metastasis in lung cancer. In addition to thrombogenesis, interaction between VE-cadherin and VEGF may be needed for successful metastasis in lung cancer.     

Tumor location determines midkine level and its association with the disease progression in colorectal cancer patients: a pilot study

Purpose

The purpose of this study was to evaluate midkine, multipotential cytokine, and growth factor in colorectal cancer (CRC) stratified by tumor location.

Methods

Midkine was assessed immunoenzymatically in paired cancerous and noncancerous tissues from 53 CRCs and referred to CRC stage, tumor location, and size, and circulating cytokine levels.

Results

Midkine was higher in cancerous versus noncancerous tissue in 98?% cases (424.2 vs. 31.1?pg/mg, p?p?=?0.005) due to higher midkine level in noncancerous rectal than colonic tissue (45.5 vs. 26.2?pg/mg, p?=?0.074). Tumor location affected midkine association with CRC stage. Midkine fold change was higher in advanced stages of rectal cancers (16.8 vs. 5.3, respectively in III/IV vs. I/II, p?=?0.013), while it tended to be lower in colonic ones (25.3 vs. 47.8, p?=?0.134). In addition, fold change in midkine level was higher in rectal N1 than N0 cancers (17.3 vs. 16.5, p?=?0.032), while it tended to be lower in colonic cancers (23.6 vs. 50.1, p?=?0.085). Midkine negatively correlated with tumor size (r?=?0.40, p?=?0.017), while it tended to positively correlate with its serum levels (r?=?0.45, p?=?0.081).

Conclusions

Midkine is differently expressed in tumors arising from colonic and rectal mucosa, where it may play diverse roles in carcinogenesis. High midkine expression in noncancerous rectal mucosa might contribute to, a characteristic for rectal cancers, higher incidence of local recurrence. Divergent expression of midkine and its association pattern ought to be taken into account while designing midkine-directed therapies for CRC.     

Management of colorectal cancer in patients with inflammatory bowel disease

Background

This study evaluated the clinicopathological features and survival rates of patients with inflammatory bowel disease who developed colorectal cancer (CRC).

Methods

A retrospective review was performed on a prospectively maintained institutional database (1981–2011) to identify patients with inflammatory bowel disease who developed CRC. Clinicopathological parameters, management and outcomes were analysed.

Results

A total of 2,843 patients with inflammatory bowel disease were identified. One thousand six hundred and forty-two had ulcerative colitis (UC) and 1,201 had Crohn’s disease (CD). Following exclusion criteria, there were 29 patients with biopsy-proven colorectal carcinoma, 22 of whom had UC and 7 had CD. Twenty-six patients had a preoperative diagnosis of malignancy/dysplasia; 16 of these were diagnosed at surveillance endoscopy. Nodal/distant metastasis was identified at presentation in 47 and 71 % of the UC and CD group, respectively. Operative morbidity for UC and CD was 33 and 17 %, respectively. Despite the less favourable operative outcomes following surgery management of UC-related CRC, overall 5-year survival was significantly better in the UC group compared to the CD group (41 vs. 29 %; p = 0.04) reflecting the difference in stage at presentation between the two groups.

Conclusions

Patients who undergo surgery for UC-related CRC have less favourable short-term outcomes but present at a less advanced stage and have a more favourable long-term prognosis than similar patients with CRC and CD.     

Identification of two new HLA-A*0201-restricted cytotoxic T lymphocyte epitopes from colorectal carcinoma-associated antigen PLAC1/CP1

Background

To explore the potential application of placenta-specific PLAC1/Cancer Placenta (CP) 1 antigen for immunotherapy in CRC patients, further identification of the cytotoxic T lymphocyte epitopes from this antigen is necessary.

Methods

We assessed the protein expression of PLAC1/CP1 using a tissue chip and immunochemistry staining in CRC samples. Simultaneously, we predicted four PLAC1/CP1-derived HLA-A*0201-restricted peptides by using reverse immunology methods. Peptide-specific CD8⁺ T cell responses were assessed by an IFN-γ release ELISPOT assay. Effector CD8⁺ T cells lyse HLA-A*0201 CRC cell line SW620 was detected in a granzyme-B release ELISPOT cytotoxicity assay.

Results

Our results indicated that PLAC1/CP1 was highly expressed in 56.7 % (55/97) of adenocarcinomas. PLAC1/CP1 protein expression was associated with CRC tumor differentiation, the tumor/node/metastasis stage, and lymph node metastasis. Two of four peptides showed high affinities in an HLA-A2 binding assay. In 66.7 % (6/9) of peripheral blood mononuclear cells of CRC samples with PLAC1/CP1 protein-positive expression, these two peptides, PLAC1/CP1 p41-50 (FMLNNDVCV) and PLAC1/CP1 p69-77 (HAYQFTYRV), were immunogenic in the induction of peptide-specific CD8⁺ T cell responses as assessed by an IFN-γ release ELISPOT assay. Furthermore, the generated effector CD8⁺ T cells could specifically lyse the PLAC1/CP1 HLA-A*0201 CRC cell line SW620 in a granzyme-B release ELISPOT cytotoxicity assay.

Conclusions

These results show that the PLAC1/CP1 antigen is a possible prognostic marker of CRC and that PLAC1/CP1 p41-50 and PLAC1/CP1 p69-77 are novel HLA-A*0201-restricted CD8⁺ T cell epitopes and potential targets for peptide-based immunotherapy in CRC patients.     

Aggressive surgery for stage IV gallbladder carcinoma; what are the contraindications?

Background/Purpose

Advanced gallbladder carcinoma with paraaortic lymph node metastasis or distant metastasis is normally considered a contraindication for surgery. Our latest analyses suggest otherwise.

Methods

Records of 166 patients who underwent surgery for stage IV gallbladder carcinoma were reviewed retrospectively. Predictors of hospital mortality and long-term survival were analyzed. Long-term survival in patients with paraaortic lymph node metastasis and/or distant metastasis was also determined.

Results

Fifteen patients were 5-year survivors, with a 5-year survival rate of 12% among the 166 patients investigated. Overall hospital mortality was 14%. Male sex and portal vein resection were independent predictors of hospital mortality. Multivariate analysis of long-term survival failed to identify independent predictors. Patients with distant metastasis were divided into two groups based on whether or not the metastases were distant from the liver. Patients with paraaortic lymph node metastasis who underwent curative resection or who had isolated liver metastasis survived longer than those with other distant metastasis or those with unresectable advanced cancer.

Conclusions

Patients with advanced gallbladder carcinoma can benefit from surgical resection even when paraaortic lymph node metastasis and/or liver metastasis are present. However, surgical indications in advanced disease should be determined on an individual basis, based on clinical status.     

High TrkB expression levels are associated with poor prognosis and EMT induction in colorectal cancer cells

Background

The neurotrophic receptor tropomyosin related kinase (TrkB) is associated with tumor progression in neuroblastoma and certain human malignancies. Recent reports indicate TrkB may participate in the epithelial–mesenchymal transition (EMT). This study investigates whether TrkB expression is associated with the clinical outcome of colorectal cancer (CRC) patients and whether TrkB induces EMT in CRC cells.

Methods

TrkB and E-cadherin expression in surgical tissue samples and clinicopathological data from 102 CRC patients were analyzed by real-time polymerase chain reaction and immunohistochemistry. The biological role of TrkB in CRC was analyzed using RNA interference against TrkB in the CRC cell line SW480 to assess tumor progression and the correlation between TrkB and E-cadherin expression.

Results

Patients with high TrkB mRNA expression in clinical samples had a significantly poorer prognosis relative to those with low TrkB levels (p?=?0.03). TrkB was inversely correlated with E-cadherin at both the mRNA and protein levels. In vitro, cell proliferation (p?=?0.02), migration (p?p?Conclusions High TrkB expression is associated with poor prognosis in CRC patients and enhanced malignant potential in terms of proliferation, migration, invasion, and anoikis inhibition in CRC cells. These results indicate TrkB could induce EMT and play an important role in CRC progression to metastasis.     

Clinical correlations of miR-21 expression in colorectal cancer patients and effects of its inhibition on DLD1 colon cancer cells

Purpose

MicroRNA-21 (miR-21) is one of the miRNAs that are frequently and highly overexpressed in tumor tissue of colorectal cancer (CRC) patients; however, only a little is known about its functional role in CRC.

Methods

We examined the expression level of miR-21 in 44 paired samples of tumoral and non-tumoral colon tissues diagnosed for CRC using TaqMan real-time PCR method. Furthermore, we used miR-21 inhibitor (anti-miR-21) to transient knockdown of miR-21 in DLD-1 colon cancer cells and examined the effects of miR-21 silencing on viability, apoptosis, chemosensitivity, cell cycle, and migration of DLD1 cells.

Results

The expression levels of miR-21 were significantly increased in CRC tumor tissue (P?<?0.0001). Significant differences in miR-21 levels were observed also between CRC tissues of patients with CRC in different clinical stages: I vs. II (P?=?0.033) and I vs. IV (P?=?0.021). Kaplan–Meier analysis proved that the miR-21 expression levels are correlated to shorter overall survival of CRC patients (P?=?0.0341). MiR-21 silencing in DLD1 cell line had no effect on the cell viability; however, when combined with chemotherapeutics (5-FU, L-OHP, and SN38), it contributed to the decrease of cell viability. Suppression of miR-21 decreased cell migration ability of DLD-1 cells by nearly 30?% (P?=?0.016).

Conclusion

We have confirmed the overexpression of miR-21 in CRC samples and its correlation with advanced disease and shorter overall survival. These findings could be described in part by the fact that CRC cells with increased expression of miR-21 have higher migration ability.     

Usefulness of plasma epigenetic changes of five major genes involved in the pathogenesis of colorectal cancer

Purpose

The purpose of present study was to investigate the methylation status of the promoter region in five genes (mothers against decapentaplegic homolog 4, fragile histidine triad protein, death-associated protein kinase 1, adenomatous polyposis coli (APC), and E-cadherin), which are known to be involved in the pathogenesis of colorectal cancer (CRC) and its clinicopathological significance.

Methods

The study subjects were 60 CRC patients, 40 patients with adenomatous colorectal polyp and 60 healthy control individuals. We further enrolled a total of 16 patients (two patients with Crohn’s disease, two patients with ulcerative colitis, one patient with serrated adenoma, and 11 patients with colorectal cancer). The methylation states of the five genes were determined in peripheral blood plasma using methylation-specific polymerase chain reaction single-strand conformation polymorphism analysis.

Results

This study showed the most sensitive epigenetic markers, E-cadherin (60 %), followed by APC (57 %), for detecting CRC. E-cadherin and APC had similar specificities and amplified 84 and 86 %, respectively, of CRC patients compared to non-CRC patients. Additionally, APC was the only marker to be significantly increased (OR?=?6.67, 95 % CI?=?1.19–23.4, P?=?0.045) and the most sensitive (57 %) and specific (89 %) marker in stage I CRC. Though we have not examined the paired cancer tissues and plasma, there was relatively high concordant rate (60–80 %) in our limited number of colorectal cancer patients.

Conclusions

Five genes, promoter methylation, in plasma were statistically significant risk factors in CRC patients. In this study, E-cad and APC genes may be particularly useful epigenetic biomarkers in plasma for the detection of CRC. Additionally, APC may able to identify early potential CRC.     

Identification of IMPDH2 as a tumor-associated antigen in colorectal cancer using immunoproteomics analysis

Background and aims

Sera from cancer patients contain tumor-specific autoantibodies directly against antigenic proteins. The identification of tumor autoantigens may have utility in cancer diagnosis, prognosis, and therapy. In this study, we used immunoproteomics analysis to identify tumor proteins that elicit humoral response in colorectal cancer (CRC).

Materials and methods

The CRC cell line HCT116 was used as a source of proteins for two-dimensional polyacrylamide gel electrophoresis and subsequent Western blot analysis in which individual serum from patients with CRC was analyzed for autoantibodies. Proteins that specifically react with sera from cancer patients were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometric analysis. In addition, the selected protein expression in tumor tissues collected from 40 patients with CRC were assessed by immunohistochemistry.

Results

An autoantibody against inosine monophosphate dehydrogenase II (IMPDH2) identified by mass spectrometry was detected in eight out of 25 patients with CRC. However, none of the 15 healthy controls demonstrated autoantibody to IMPDH2.The expression of IMPDH2 in tumor tissue was significantly higher in patients with CRC than that in healthy subjects.

Conclusions

The result confirmed that the immunoproteomics analysis holds considerable promise for the discovery of tumor-associated antigens. IMPDH2 may be a protein biomarker and novel therapeutic target in CRC.     

Overexpression of Lgr5 correlates with resistance to 5-FU-based chemotherapy in colorectal cancer

Background

The leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) is an adult intestinal stem cell marker frequently detected in human colorectal cancers (CRCs). However, the value of Lgr5 level in CRC prognosis and treatment prediction has not been well characterized.

Methods

We examined Lgr5 expression in 384 formalin-fixed paraffin-embedded CRC specimens from 296 CRC patients, including 64 patients treated with 5-fluorouracil (5-FU)-based chemotherapy. The effects of Lgr5 on cell proliferation, survival, and drug resistance were examined in cultured CRC cells.

Results

Elevated expression of Lgr5 was observed in CRC tissues, and Lgr5 protein levels were significantly correlated with an advanced American Joint Committee on Cancer stage (P?<?0.001), T stage (P?<?0.001), N stage (P?<?0.001), and distant metastasis (P?<?0.001). High expression levels of Lgr5 were significantly associated with shorter disease-free survival (P?<?0.001) and shorter cancer-specific survival (P?=?0.007) in CRC patients. Among the chemotherapy-treated subgroups, patients with low Lgr5 level showed a better response rate (65 %) than patients with high Lgr5 level (37 %) towards 5-FU-based treatment (P?=?0.025). In cultured CRC cell lines, knocking down Lgr5 suppressed cell proliferation and colony formation ability, while it enhanced apoptosis and rendered cells more sensitive to chemotherapeutic agents. In contrast, overexpression of Lgr5 increased cell proliferation and enhanced chemoresistance.

Conclusion

These results suggest that elevated Lgr5 level is associated with CRC progression and treatment response and has the potential to serve as a therapeutic target in CRC patients.     

C-ERC/mesothelin provokes lymphatic invasion of colorectal adenocarcinoma

Background

Lymph node metastasis is a key event of colorectal cancer (CRC) progression. Mesothelin is expressed in various types of malignant tumor and associated with an unfavorable prognosis. The full-length mesothelin (Full-ERC) is cleaved by protease into membrane-bound C-ERC/mesothelin and N-ERC/mesothelin which is secreted into the blood. The aim of this study was to examine the biological role of mesothelin in CRC by clinicopathological analysis and in vitro lymphatic invasion assay.

Methods

Ninety-one cases of CRC specimens were immunohistochemically examined and the localization of mesothelin in luminal membrane and/or cytoplasm was also evaluated. Lymphatic invasion assay was also performed using the human CRC cell line, WiDr, which was transfected with Full-, N- and C-ERC/mesothelin expression plasmids (Full-WiDr, N-WiDr and C-WiDr).

Results

Immunohistochemically, “luminal membrane positive” of mesothelin was identified in 37.4 %, and correlated with lymphatic permeation and lymph node metastasis, but not with patients’ prognosis. Interestingly, among the patients with lymph node metastasis (N = 38), “luminal membrane positive” of mesothelin significantly correlated with unfavorable patients’ outcome. In addition, lymphatic invasion assay revealed that Full-WiDr and C-WiDr more significantly invaded human lymphatic endothelial cells than the Mock-WiDr (P < 0.01).

Conclusion

The luminal membrane expression of mesothelin was associated with unfavorable prognosis of CRC patients with lymph node metastasis. Moreover, this is the first report to prove the biological function of C-ERC/mesothelin associated with lymphatic invasion of cancer in vitro.     

Management of peritoneal carcinomatosis from colorectal cancer: review of the literature

Background

Today, we do not have a universally accepted evidence on how to treat peritoneal carcinomatosis (PC) from colorectal cancer (CRC) in international guidelines.

Methods

The present study is a review of the literature investigating current strategies to treat CRC PC.

Results

Despite the progresses of systemic chemotherapy, the presence of PC among patients with metastatic CRC reduces the overall survival to 30 %, and only 4 % of patients with PC from CRC treated are alive for 5 years. Many trials evaluate the combined treatment of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for CRC PC, suggesting a survival benefit in highly selected patients. Only one trial is randomized and presents some biases. The two main prognostic factors are Peritoneal Cancer Index (PCI) and completeness of cytoreduction score (CC score). There is no universal agreement on how to approach the synchronous presence of PC and liver metastasis with a curative intent during the same procedure. A growing interest among the scientific community has arisen about systematic second-look surgery and HIPEC treatment in high-risk patients.

Conclusion

Current evidences suggest that CRS and HIPEC might be beneficial in highly selected patients affected with PC from CRC. Anyway, today, there is a shortage of well-designed phase 3 trials.     

Diabetes and prognosis in a breast cancer cohort

Purpose

Epidemiological studies indicated that type 2 diabetes mellitus may increase breast cancer risk and mortality. The aim of this retrospective cohort study was to examine the effect of diabetes on the clinical course and the prognosis of early stage breast cancer in relation to tumour and patient characteristics.

Methods

The cohort analyzed in this study consisted of 4,056 patients with invasive primary breast cancer. We compared overall survival, distant metastasis-free survival and local recurrence free survival between breast cancer patients with and without diabetes.

Results

In our cohort 276 breast cancer patients (6.8%) were affected by diabetes compared to 3,780 patients (93.2%) without diabetes. Women with diabetes were significantly older, had larger tumours, and a higher rate of lymph node involvement. After a follow-up period of 5?years, stratification for age and adjustment for other prognostic factors, overall mortality following breast cancer was significantly higher in diabetic breast cancer patients (hazard ratio, HR 1.92; 95% confidence interval, CI 1.49?C2.48). We found no significant differences in distant metastasis-free survival and local recurrence free survival between the two groups, but we found a slightly significant higher rate of distant metastasis in the group of patients with diabetes and oestrogen receptor negative tumours (HR 2.28; CI 1.31?C3.97).

Conclusion

In this study, patients with diabetes and oestrogen receptor negative breast cancer had a more than 2-fold higher risk for distant metastasis compared to patients without diabetes. Diabetes was also associated with an almost 2-fold increase in mortality within the 5?years follow-up period.     

Quantitative analysis of TEM-8 and CEA tumor markers indicating free tumor cells in the peripheral blood of colorectal cancer patients

Background

Colorectal cancer (CRC) remains the third most common cancer in the world. Approximately in 50 percent of patients, metastatic disease is a major cause of death. Therefore, early diagnosis of CRC is crucial for a successful outcome. For the detection of circulating cancer cells, this study applied a sensitive method that employed specific tumor markers for early detection.

Methods

A total of 80 blood samples from 40 CRC patients and 40 age-matched healthy controls were collected for the study. The circulating mRNA levels of two CRC tumor markers, tumor endothelial marker 8 (TEM-8) and carcinoembryogenic antigen (CEA) were evaluated using an absolute quantitative real-time PCR assay in a Stratagene Mx-3000P real-time PCR system. GAPDH was used as the endogenous control.

Results

TEM-8 and CEA were primarily detected more in the CRC patients rather than in the controls: 22/40 vs 9/40, p=0.009 and 30/40 vs 11/40, p=0.00054, respectively. In the CRC patients, the mRNA level of these markers was significantly higher in comparison to the normal controls (p=0.018 and 0.01). The overall sensitivity of this panel was 65% with a specificity of 75%. Statistical analysis for demographic variants did not reach significant values.

Conclusions

TEM-8 and CEA markers were detected more frequently and in significantly higher levels in the blood samples of patients compared with samples from age-matched healthy controls. The copy number of CEA and TEM-8 mRNA, as detected by a real-time quantitative PCR, appears to be a promising marker for evaluating the risk of tumor spread.     

The Role of Primary Care Physicians in Improving Colorectal Cancer Screening in Patients with HIV

BACKGROUND

As HIV positive patients live longer, they become susceptible to the development of non-AIDS defining malignancies. Little is known about routine cancer screening practices in that population and the factors associated with cancer screening.

OBJECTIVE

Evaluate 1) the proportion of patients with HIV who had any type of colorectal cancer (CRC) screening and 2) whether having a primary care physician (PCP) or seeking care in an integrated care practice is associated with higher CRC screening.

DESIGN

A cross-sectional chart abstraction study of patients with HIV enrolled in the Philadelphia Medical Monitoring Project (MMP).

PARTICIPANTS

MMP participants age 50 and older.

MAIN MEASURES

CRC screening defined as having a documented colonoscopy, sigmoidoscopy, barium enema, or fecal occult blood test after the age of 50.

KEY RESULTS

Out of 123 chart abstractions performed, 115 had a complete clinical record from MMP. The majority of the population was male (71.3%), Black/Hispanic (73.8%) and between the age of 50 and 59 (71.3%). 45.2% of patients did not have a PCP. The overall proportion of patients who received CRC screening was 46.9%. Having a documented PCP was the only factor strongly associated with CRC screening. Rates of screening were 66.7% among those with a PCP versus 28.5% among those without a PCP (??² p?p?CONCLUSIONS Having a PCP significantly increases the likelihood of receiving CRC screening in patients with HIV. Competency in addressing primary care needs in HIV clinics will only become more important as patients with HIV age.