The Dilemma of Breast Cancer Treatment and Existing Collagen Vascular Disease: A Case of Scleroderma and Review of the Literature.

Collagen vascular diseases present a treatment dilemma for patients with breast cancer. Due to the potential for severe, acute, and late complications of radiation therapy, a history of collagen vascular disease (CVD) is a relative contraindication to breast-conserving treatment. We present a case of early stage breast cancer in a patient with severe scleroderma treated with breast-conserving surgery without radiation and a brief review of the published literature regarding the therapeutic approach to the patient with CVD and breast cancer.

Nanomagnetic levitation three-dimensional cultures of breast and colorectal cancers.

BACKGROUND: Innovative technologies for drug discovery and development, cancer models, stem cell research, tissue engineering, and drug testing in various cell-based platforms require an application similar to the in vivo system. MATERIALS AND METHODS: We developed for the first time nanomagnetically levitated three-dimensional (3-D) cultures of breast cancer (BC) and colorectal cancer (CRC) cells using carbon-encapsulated cobalt magnetic nanoparticles. BC and CRC xenografts grown in severe combined immunodeficient (SCID) mice were evaluated for N-cadherin and epidermal growth factor receptor expressions. These phenotypes were compared with two-dimensional and 3-D cultures grown in a gel matrix. RESULTS: The BC and CRC cells grown by magnetic levitation formed microtissues. The levitated cultures had high viability and were maintained in culture for long periods of time. It has been observed that N-cadherin and epidermal growth factor receptor activities were highly expressed in the levitated 3-D tumor spheres and xenografts of CRC and BC cells. CONCLUSIONS: Nanomagnetically levitated 3-D cultures tend to form stable microtissues of BC and CRC and maybe more feasible for a range of applications in drug discovery or regenerative medicine.

Robust Synthesis of Targeting Glyco-nanoparticles for Surface Enhanced Resonance Raman Based Image-Guided Tumor Surgery.

Surface Enhanced Resonance Raman (SERS) is a powerful optical technique, which can help enhance the sensitivity of Raman spectroscopy aided by noble metal nanoparticles (NPs). However, current SERS-NPs are often suboptimal, which can aggregate under physiological conditions with much reduced SERS enhancement. Herein, a robust one-pot method has been developed to synthesize SERS-NPs with more uniform core diameters of 50 nm, which is applicable to both non-resonant and resonant Raman dyes. The resulting SERS-NPs are colloidally stable and bright, enabling NP detection with low-femtomolar sensitivity. An algorithm has been established, which can accurately unmix multiple types of SERS-NPs enabling potential multiplex detection. Furthermore, a new liposome-based approach has been developed to install a targeting carbohydrate ligand, i.e., hyaluronan, onto the SERS-NPs bestowing significantly enhanced binding affinity to its biological receptor CD44 overexpressed on tumor cell surface. The liposomal HA-SERS-NPs enabled visualization of spontaneously developed breast cancer in mice in real time guiding complete surgical removal of the tumor, highlighting the translational potential of these new glyco-SERS-NPs.

Cholesterol crystals induce mechanical trauma, inflammation, and neo-vascularization in solid cancers as in atherosclerosis.

Background and aims: Cancer and atherosclerosis share common risk factors and inflammatory pathways that promote their proliferation via vascular endothelial growth factor (VEGF). Because CCs cause mechanical injury and inflammation in atherosclerosis, we investigated their presence in solid cancers and their activation of IL-1ß, VEGF, CD44, and Ubiquityl-Histone H2B (Ub-H2B), that promote cancer growth. Methods: Tumor specimens from eleven different types of human cancers and atherosclerotic plaques were assessed for CCs, free cholesterol content and IL1-ß by microscopy, immunohistochemistry, and biochemical analysis. Breast and colon cancer cell lines were cultured with and without CCs to select for expression of VEGF, CD44, and Ub-H2B. Western blot and immunofluorescence were performed on cells to assess the effect of CCs on signaling pathways. Results: Cancers displayed higher CC content (+2.29 ± 0.74 vs +1.46 ± 0.84, p < 0.0001), distribution (5.06 ± 3.13 vs 2.86 ± 2.18, p < 0.001) and free cholesterol (3.63 ± 4.02 vs 1.52 ± 0.56 µg/mg, p < 0.01) than cancer free marginal tissues and similarly for atherosclerotic plaques and margins (+2.31 ± 0.51 vs +1.44 ± 0.79, p < 0.02; 14.0 ± 5.74 vs 8.14 ± 5.52, p < 0.03; 0.19 ± 0.14 vs 0.09 ± 0.04 µg/mg, p < 0.02) respectively. Cancers displayed significantly increased expression of IL1-ß compared to marginal tissues. CCs treated cancer cells had increased expression of VEGF, CD44, and Ub-H2B compared to control. By microscopy, CCs were found perforating cancer tumors similar to plaque rupture. Conclusions: These findings suggest that CCs can induce trauma and activate cytokines that enhance cancer growth as in atherosclerosis.

21-Gene recurrence scores: racial differences in testing, scores, treatment, and outcome.

BACKGROUND: African American (AA) women experience higher breast cancer mortality than white (W) women. These differences persist even among estrogen receptor (ER)-positive breast cancers. The 21-gene recurrence score (RS) predicts recurrence in patients with ER-positive/lymph node-negative breast cancer according to RS score-low risk (RS, 0-18), intermediate risk (RS, 19-31), and high risk (RS, >31). The high-risk group is most likely to benefit from chemotherapy, to achieve minimal benefit from hormonal therapy, and to exhibit lower ER levels (intrinsically luminal B cancers). In the current study, the authors investigated racial differences in RS testing, scores, treatment, and outcome. METHODS: Tumor registry data from 3 Atlanta hospitals identified women who were diagnosed with breast cancers during 2005 through 2009. Medical record abstraction provided information on RS and other tumor/treatment factors. Statistical analyses used chi-square/exact tests and logistic regression. RESULTS: Of 2186 patients, including 1192 AA women and 992 W women, 853 women had stage I or II, ER-positive/lymph node-negative disease and, thus, were eligible for RS testing (AA = 372 [31.2%]; W = 481 [48.5%]; P < .0001); and 272 women (31.8%) received testing (AA = 76 [20.4%]; W = 196 [40.7%]; P < .0001). Tumors were distributed into the following groups according to risk: low risk (n = 133), medium risk (n = 113), and high risk (n = 26). The mean RS did not differ by race, but risk groups did (low-risk group: 46.1% vs 50% for AA women and W women, respectively; high-risk group: 15.8% vs 7.1%, respectively; P = .043). In multivariate analyses, AA race (odds ratio, 3.6) was associated independently with high risk scores. CONCLUSIONS: AA women were half as likely as W women to receive 21-gene RS testing but were 2-fold more likely to be categorized as high risk. The current data suggested that testing guidelines are not applied equivalently, testing bias may attenuate racial differences in RS, and disparate outcomes may be explained in part by differences in RS, although compliance and pharmacogenomics also may play a role.

Pseudoangiomatous stromal hyperplasia (PASH) of the breast: a series of 24 patients.

Pseudoangiomatous stromal hyperplasia (PASH) is a benign mesenchymal proliferative lesion of the breast. In 2005, only 109 cases had been reported since its initial description in 1986 by Vuitch et al. Our 24 cases represent one of the largest series to be reported from a single institution. We retrospectively reviewed data from 2004 to 2010 of patients diagnosed with PASH by surgical excision or image-guided biopsy. All pathological specimens were reviewed by a single pathologist. The samples were stained for estrogen and progesterone receptors (ER and PR), CD34, and the lymphatic marker D2-40. All but one of 24 (96%) patients presented with breast masses either on imaging or clinically. Fourteen of the 24 patients (58%) were diagnosed on surgical excision, 10 (42%) diagnosed with core needle biopsy, and five (20%) were diagnosed using both techniques. The tumors ranged in size from 0.3 cm to 7.0 cm. All women except two were premenopausal or perimenopausal at diagnosis. Nineteen samples were available for hormonal receptor staining and of these 18 of 19 (95%) were ER or PR positive. PASH was diagnosed in two men, a transgender male on hormones and the other with gynecomastia. The patients' ages ranged from 18 to 86 years old. In addition to PASH other benign histopathological findings include stromal fibrosis and atypical ductal or lobular hyperplasia. Imaging revealed no distinguishing feature for PASH with benign histology. One patient had synchronous ductal carcinoma in-situ (DCIS). Patients were treated with local excision or observation. This study suggests that PASH is primarily a diagnosis of premenopausal and perimenopausal women. Our series supports a hormonal basis for its development due to the positive staining for hormonal receptors. Management is conservative surgery for larger masses with careful observation being an option in patients not at high risk for breast cancer.

CXCR4-gp120-IIIB interactions induce caspase-mediated apoptosis of prostate cancer cells and inhibit tumor growth.

CXC chemokine receptor 4 (CXCR4) has been implicated in prostate cancer metastasis and this receptor also acts as a coreceptor for HIV-1 120-kDa glycoprotein variant IIIB (gp120-IIIB). The interaction between CXCR4 and gp120-IIIB has been shown to mediate apoptosis of both immune and endothelial cells. In this study, we have examined the effects of gp120-IIIB on hormone-refractory prostate cancer cells (PC3 and DU145) in vitro and tumor growth in vivo. Normal prostatic epithelial (PrEC) and prostate cancer cell lines were treated with gp120-IIIB with or without anti-CXCR4 antibody. Caspase expression was evaluated by real-time PCR and active caspase assays. Apoptosis was determined by flow cytometry. gp120-IIIB treatment correlated with active caspase-3 and -9 expression and apoptosis of prostate cancer cells but not PrEC cells. This effect was significantly inhibited after CXCR4 blockade. PC3 and DU145 tumor-bearing mice received intraperitoneal injections of gp120-IIIB and controls received bovine serum albumin in PBS. PC3 and DU145 tumor sizes were measured over time and excised tumors were evaluated for CD44, CD34, lymphatic endothelial cell marker LYVE-1, active caspase-3, and active caspase-9 expression by immunohistochemistry. The tumor size in mice receiving gp120-IIIB was significantly smaller than compared with tumors in control mice. This regression was associated with significant decreases in CD44, CD34, and LYVE-1 and increases in active caspase-3 and -9 expression. These results suggest that gp120-IIIB induced apoptosis in prostate cancer cells and reduced tumor-associated lymphoendothelial cells.

Functional consequence of the p53 codon 72 polymorphism in colorectal cancer.

BACKGROUND: The codon 72 polymorphism in p53 has been implicated in colorectal cancer (CRC) risk, prognosis and CRC health disparities. We examined the functional consequence of this polymorphism in CRC. EXPERIMENTAL DESIGN: Plasmids (pCMV6) that express different phenotypes of p53 [p53 wild type (wt) at codon 72 (R72wt), R72wt with mutation at codon 273 cysteine (R72273Cys), p53 mutation at codon 72 (P72wt) and P72wt with mutation at codon 273 (P72273Cys)] were constructed. The CRC cell line Caco2, which does not express p53 for in vitro studies, was used as host. CRC xenografts were established in severe combined immunodeficient (SCID) mice using established cell lines. CRC surgical specimens, corresponding normal colon, and tumor xenografts were sequenced for codon 72 polymorphism of p53. Proteins signaling mechanisms were evaluated to assess the functional consequence of P72 phenotype of p53. RESULTS: This study demonstrated a significantly increased survival of cells expressing P72wt, mutant phenotype, versus R72wt phenotype. WB analyses revealed that P72wt induced activation of p38 and RAF/MEK/ extracellular signal-regulated kinase (ERK) MAP kinases. Activation of CREB was found to be higher in tumors that exhibit P72 phenotype. Metastatic lesions of CRC expressed more phospho-CREB than non-metastatic lesions. The expression of P72wt promoted CRC metastasis. CONCLUSIONS: P72 contributes to the aggressiveness of CRC. Because P72 is over-expressed in CRC, specifically in African-American patients, this suggests a role for P72 in cancer health disparities. This work was supported by NIH/NCI Workforce Diversity Grant R21-CA171251 & U54CA118948.

Effects of HIV-1 Nef, a cytotoxic viral protein, on the growth of primary colorectal cancer.

Colorectal cancer is the third leading cause of cancer deaths in American men and women. We describe the cytotoxic use of HIV-1 Nef protein and a cytotoxic peptide identified within the HIV-1 Nef structure in targeting human cancer cells in vitro and in vivo in a human xenograft model. A human colorectal tumor was implanted and propagated in the subcutaneous tissue of SCID mice. The mice were injected biweekly with the Nef apoptotic peptide. The tumor treated with Nef peptide underwent significant growth inhibition by as much as 300 percent when compared to the control (untreated) tumors. The Nef peptides were found to have an apoptotic effect on the human colon tumor similar to the effect seen on CD4 cells when the viral protein is secreted by the HIV-1 virus infected cells. The evidence from the xenograft mouse model suggests that the Nef peptides can be used to inhibit human colorectal cancer growth.

Nef-M1, a peptide antagonist of CXCR4, inhibits tumor angiogenesis and epithelial­to­mesenchymal transition in colon and breast cancers.

The Nef-M1 peptide competes effectively with the natural ligand of CXC chemokine receptor 4 (CXCR4), stromal cell-derived factor 1-alpha, to induce apoptosis and inhibit growth in colon cancer (CRC) and breast cancer (BC). Its role in tumor angiogenesis, and epithelial-to-mesenchymal transition (EMT) regulation, key steps involved in tumor growth and metastasis, are unknown. We evaluated the angioinhibitory effect of Nef-M1 peptide and examined its role in the inhibition of EMT in these cancers. Colon (HT29) and breast (MDA-MB231) cancer cells expressing CXCR4 were studied in vitro and in xenograft tumors propagated in severe combined immunodeficient mice. The mice were treated intraperitoneally with Nef-M1 or scrambled amino acid sequence of Nef-M1 (sNef-M1) peptide, a negative control, starting at the time of tumor implantation. Sections from tumors were evaluated for tumor angiogenesis, as measured by microvessel density (MVD) based on immunostaining of endothelial markers. In vitro tumor angiogenesis was assessed by treating human umbilical vein endothelial cells with conditioned media from the tumor cell lines. A BC cell line (MDA-MB 468) which does not express CXCR4 was used to study the actions of Nef-M1 peptide. Western blot and immunofluorescence analyses assessed the effect of Nef-M1 on tumor angiogenesis and EMT in both tumors and cancer cells. Metastatic lesions of CRC and BC expressed more CXCR4 than primary lesions. It was also found that tumors from mice treated with sNef-M1 had well established vascularity, while Nef-M1 treated tumors had very poor vascularization. Indeed, the mean MVD was lower in tumors from Nef-M1 treated mice than in sNef-M1 treated tumors. Nef-M1 treated tumor has poor morphology and loss of endothelial integrity. Although conditioned medium from CRC or BC cells supported HUVEC tube formation, the conditioned medium from Nef-M1 treated CRC or BC cells did not support tube formation. Western blot analyses revealed that Nef-M1 effectively suppressed the expression of VEGF-A in CRC and BC cells and tumors. This suggests that Nef-M1 treated CRC and BC cells are more consistent with E-cadherin signature, and thus appears more epithelial in nature. Our data indicate that Nef-M1 peptide inhibits tumor angiogenesis and the oncogenic EMT process. Targeting the chemokine receptor, CXCR4, mediated pathways using Nef-M1 may prove to be a novel therapeutic approach for CRC and BC.

Phyllodes tumors in African American women.

BACKGROUND: Phyllodes is a rare tumor accounting for less than 1% of all breast neoplasms. Studies defining clinical predictors of malignant phyllodes (MP) are rare and inconsistent. Furthermore, MP occurrence in African American (AA) women has never been analyzed. This study will delineate clinical and pathologic features in AA patients that may reasonably predict the probability of malignancy. METHODS: A retrospective study of clinical records was carried out for 50 AA patients diagnosed with phyllodes tumors (PT) and treated between 1982 and 2012. Patients' charts were analyzed regarding demographics, pathology findings, and treatment. RESULTS: The diagnosis of benign disease was made in 40 (78%), borderline in 3 (6%), and malignancy in 7 (14%) patients; however, 1 patient (2%) had mixed phyllodes with ductal carcinoma in situ. The mean age was significantly different for patients with benign disease (33 years) compared with those with malignancy (54 years; P < .001). The average tumor size was twice as large (11.8 vs 4.1 cm; P = .029) and mitoses were higher with 50% of MPs having greater than 5 per 10 high power fields. Although rare, nodal metastasis, ulceration, and multicentric disease occurred only in MP. CONCLUSIONS: Among AA patients with phyllodes tumors, those with malignant tumors were older and had larger tumors and higher mitotic indices than those with benign disease. AA patients also displayed some of the more rare features of advanced disease and presented with malignancy near the highest reported frequency.

Unusual complications of long-term percutaneous gastrostomy tubes.

Percutaneous endoscopic gastrostomy (PEG) has been popular since it was introduced in 1980. Gastrostomy tubes left in place for long periods often result in unusual complications. Complications may also result from simply replacing a long-term indwelling tube. Five patients who had gastrostomy tubes in place for as long as 4 years are presented and their complications reviewed. Various methods used in treating these complications are discussed, and suggestions for their prevention are given. Gastrointestinal erosion and jejunal perforation following migration of the gastrostomy tube, persistent abdominal wall sinus tracts, and separation of the flange head with small bowel obstruction were encountered. Reinsertion of a gastrostomy tube through a tract prior to adequate maturation was also noted to lead to complications. Complications may result from gastrostomy tubes left in place for extended periods of time and during replacement procedures. Awareness of such complications along with education of caregivers and timely intervention by the endoscopist may prevent such occurrences. In some cases one can only hope to minimize morbidity.

Debilitating lymphedema of the upper extremity after treatment of breast cancer.

Lymphedema after mastectomy occurs with a frequency as high as 30%. The incidence increases with more radical surgical dissection, as was often seen with radical mastectomies in the late 1800s. This is one aspect of breast surgery that has been greatly neglected. Surgery has often been deemed a success if the malignancy is eradicated. Patients may complain of symptoms as minor as arm heaviness to major ones such as massive chronic swelling, as was the case with our patient. The patient presented here had increasing lymphedema during a 14-year period after modified radical mastectomy and radiation therapy for advanced breast cancer. This condition had progressed to incapacitation of the extremity and a patient who as a result had become an invalid. The massively edematous extremity revealed no signs of recurrent disease or malignant degeneration. She underwent surgical intervention and physical therapy as procedures of choice to restore function.

Thigh compartment syndrome after acute ischemia.

Thigh compartment syndrome (TCS) is a poorly recognized clinical condition that may follow reperfusion of acutely ischemic thigh muscles. The anterior muscle group appears to be at greatest risk because of its layered arrangement. Intense pain, swelling, and elevated compartment pressures characterize the early presentation in the affected muscle group. If untreated myonecrosis, myoglobinuria, and renal failure may result. TCS was observed in a patient who was treated for a gunshot wound to the left thigh. The superficial femoral and profunda femoris veins as well as the profunda femoris artery were disrupted. The superficial femoral vein and profunda femoris artery injuries were repaired but the mangled branches of the profunda femoris vein were ligated. Postoperatively he developed intense thigh pain, swelling, and elevated compartment pressures. Lateral thigh fasciotomy, extensive debridement of necrotic muscle, and delayed wound closure resulted in a full recovery. Physicians should recognize the numerous clinical circumstances that could lead to TCS--particularly those associated with trauma or physical activity. Timely recognition and intervention may be both limb and life saving. Associated irreparable injury to the profunda femoris vein may aggravate this condition.

Venous claudication in a child with thrombophilia.

Deep venous thrombosis (DVT) rarely occurs in active children. Its presence usually suggests an inherited or acquired hypercoagulable state. Occasionally mechanical obstruction may be the inciting factor in this process. Initial management usually consists of sequential heparin and warfarin anticoagulation. We present the management of DVT in an adolescent girl with elevated levels of C-reactive protein and lupus anticoagulant. Venous claudication and severe lower-extremity swelling on ambulation complicated her course. After more than 2 weeks of conservative therapy with anticoagulation thrombolytic therapy was instituted. This was terminated early because of mild hematuria. However, follow-up duplex scan at 2 years has shown complete resolution of the iliofemoral thrombosis. Spontaneous DVT in children differ from that in adults in that an underlying etiology can usually be uncovered. These differences are explored.

Recurrent ischemia in a young man with the antiphospholipid syndrome.

Recurrent thromboses, cerebral disease, miscarriages, and antiphospholipid antibodies are characteristic of the antiphospholipid syndrome. A 31-year-old man presented with limb ischemic and isolated right ventricular failure. Antiphospholipid syndrome was suspected and limb salvage was accomplished by anticoagulation and tibial- to-plantar artery bypass surgery. However, recurrent ischemic episodes were successfully treated with thrombolytic therapy and anticoagulants. The surgeon should be aware that patients with antiphospholipid antibodies and lupus anticoagulant antibodies have a high propensity for recurrent arterial thromboses and should use multiple therapeutic approaches to effect successful long-term limb salvage.

Metachronous thromboses and myocardial infarctions in a 32-year-old woman with antiphospholipid antibodies.

Metachronous thromboses in multiple vascular beds in a patient younger than 40 years is often suggestive of an acquired or congenital thrombophilic disorder. We present the case of a 32-year-old African American woman who presented to the emergency room with a painful right neck mass and a right hemispheric transient ischemic attack. She had 2 prior admissions for recurrent myocardial infarctions, hypertensive crises, congestive heart failure, and a left ventricular thrombus. Her warfarin therapy expired 2 weeks before her current admission. Our expanded evaluation for thrombophilia revealed high antiphospholipid antibody levels. High-dose anticoagulants were administered without further recurrence or complications. The antiphospholipid antibody syndrome should be considered early in the differential diagnosis as an important cause of recurrent, unusual, or unexplained thromboses in young patients. Education and patient compliance are vital to successful long-term medical management.

Prognostic significance and gene expression profiles of p53 mutations in microsatellite-stable stage III colorectal adenocarcinomas.

Although the prognostic value of p53 abnormalities in Stage III microsatellite stable (MSS) colorectal cancers (CRCs) is known, the gene expression profiles specific to the p53 status in the MSS background are not known. Therefore, the current investigation has focused on identification and validation of the gene expression profiles associated with p53 mutant phenotypes in MSS Stage III CRCs. Genomic DNA extracted from 135 formalin-fixed paraffin-embedded tissues, was analyzed for microsatellite instability (MSI) and p53 mutations. Further, mRNA samples extracted from five p53-mutant and five p53-wild-type MSS-CRC snap-frozen tissues were profiled for differential gene expression by Affymetrix Human Genome U133 Plus 2.0 arrays. Differentially expressed genes were further validated by the high-throughput quantitative nuclease protection assay (qNPA), and confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and by immunohistochemistry (IHC). Survival rates were estimated by Kaplan-Meier and Cox regression analyses. A higher incidence of p53 mutations was found in MSS (58%) than in MSI (30%) phenotypes. Both univariate (log-rank, P = 0.025) and multivariate (hazard ratio, 2.52; 95% confidence interval, 1.25-5.08) analyses have demonstrated that patients with MSS-p53 mutant phenotypes had poor CRC-specific survival when compared to MSS-p53 wild-type phenotypes. Gene expression analyses identified 84 differentially expressed genes. Of 49 down-regulated genes, LPAR6, PDLIM3, and PLAT, and, of 35 up-regulated genes, TRIM29, FUT3, IQGAP3, and SLC6A8 were confirmed by qNPA, qRT-PCR, and IHC platforms. p53 mutations are associated with poor survival of patients with Stage III MSS CRCs and p53-mutant and wild-type phenotypes have distinct gene expression profiles that might be helpful in identifying aggressive subsets.

Evaluation of lymph node numbers for adequate staging of Stage II and III colon cancer.

BACKGROUND: Although evaluation of at least 12 lymph nodes (LNs) is recommended as the minimum number of nodes required for accurate staging of colon cancer patients, there is disagreement on what constitutes an adequate identification of such LNs. METHODS: To evaluate the minimum number of LNs for adequate staging of Stage II and III colon cancer, 490 patients were categorized into groups based on 1-6, 7-11, 12-19, and ≥ 20 LNs collected. RESULTS: For patients with Stage II or III disease, examination of 12 LNs was not significantly associated with recurrence or mortality. For Stage II (HR = 0.33; 95% CI, 0.12-0.91), but not for Stage III patients (HR = 1.59; 95% CI, 0.54-4.64), examination of ≥20 LNs was associated with a reduced risk of recurrence within 2 years. However, examination of ≥20 LNs had a 55% (Stage II, HR = 0.45; 95% CI, 0.23-0.87) and a 31% (Stage III, HR = 0.69; 95% CI, 0.38-1.26) decreased risk of mortality, respectively. For each six additional LNs examined from Stage III patients, there was a 19% increased probability of finding a positive LN (parameter estimate = 0.18510, p < 0.0001). For Stage II and III colon cancers, there was improved survival and a decreased risk of recurrence with an increased number of LNs examined, regardless of the cutoff-points. Examination of ≥7 or ≥12 LNs had similar outcomes, but there were significant outcome benefits at the ≥20 cutoff-point only for Stage II patients. For Stage III patients, examination of 6 additional LNs detected one additional positive LN. CONCLUSIONS: Thus, the 12 LN cut-off point cannot be supported as requisite in determining adequate staging of colon cancer based on current data. However, a minimum of 6 LNs should be examined for adequate staging of Stage II and III colon cancer patients.

miRNAs as biomarkers for management of patients with colorectal cancer.

miRNAs serve as micromanagers, negatively regulating gene expression. Since altered miRNA expression is implicated in the pathobiology of various cancers, including colorectal cancers (CRCs), these molecules serve as potential therapeutic targets. Manipulation of miRNAs may offer an alternative therapy for chemo- and radio-resistant CRCs. For CRC patients, miRNA expression patterns can be used for diagnosis, and to predict prognosis and efficacy of therapy. This article describes the methodological approaches for miRNA measurement, their function in the pathobiology of CRCs and their potential clinical utility.